Genetics Institute Inc v Johnson & Johnson

official notice

decision of A DEPUTY commissioner of patents

Application : No. 621535 in the name of GENETICS INSTITUTE INC.

Title: Method for the production of erythropoietin

Action: Opposition by JOHNSON & JOHNSON

Decision: Issued .
Abstract
Prior claim is the modern statutory equivalent of the requirement of scire facias, that the King should ‘not grant by letters patent the self same thing to several persons’. The principal question to be asked is whether, as a matter of substance, the claims define the same invention. While there were differences in specific integers set out in the various claims, those differences did not give rise to a different invention. The majority of claims were found to be prior claimed by the claims of one or other of patent application 600650 or 657555.
The present objection of prior claim was based on patent applications, not a granted patent. Ss.59(1) and 60(4) of the 1952 Act give the Commissioner a broad discretion regarding whether the application should proceed to grant in the face of the objection. Unless the objection of prior claim is removed by amendment, the present application is not to proceed to grant before both application 600650 (currently on appeal) and 657555 (currently in opposition) are either granted, lapsed, refused, or withdrawn. However the existence of other applications claiming priority from 600650 by way of being divisionals, will not prevent the grant of a patent on the present application unless (i) a patent is granted on such an application and (ii) the objection of prior claim by that patent is made out.

patents act 1990

decision of a deputy commissioner of patents

Re:Patent Application No. 621535 in the name of Genetics Institute Inc, and opposition thereto by Johnson & Johnson.

background

Patent application No. 621535 by Genetics Institute Inc (GI) was lodged under the Patents Act 1952 on 3 December 1985, and was advertised accepted under the Patents Act 1990 on 19 March 1992. Johnson & Johnson (J&J) filed a notice of opposition on 19 June 1992. As a consequence, the opposition is proceeding under Part V of the Patents Act 1952, together with the procedures of Chapter 5 of the Patent regulations 1991.

During the course of preparing evidence, J&J sought a deferment of the opposition proceedings on the basis that the primary ground of the opposition was an objection of prior claim based on patent application 600650. They argued that the opposition ought not proceed, nor the evidence be completed, until application 600650 had been either granted, refused, ceased, or withdrawn. The Commissioner did not accept this submission - both in a request for an extension of time to serve evidence (Genetics Inst v Johnson & Johnson 27 IPR 277) and in subsequent correspondence.

It is appropriate to note the current status of 600650. That application was opposed inter alia by the present applicant, and I issued my decision in that opposition in October 1995. The present applicant has appealed that decision. The applicant of 600650 (Kirin-Amgen, hereafter referred to as ‘KA’) has sought leave to amend the specification; they have also sought to have those amendments dealt with by the court (Genetics Institute v Kirin-Amgen (1996) AIPC ¶91-256, 34 IPR 513), and have now requested that the amendments before the Commissioner be held in abeyance as they are being pressed before the Court. Consequently at this time it is not possible to determine whether or when a patent will be granted on that application, nor the final scope of the claims of any patent that might be granted. It is also appropriate to note the relationship of the present opponent to patent application 600650 – I understand Johnson & Johnson to be the Australian licensee of 600650.

The opposition was heard in Canberra over 13 to 15 May 1996. The applicant was represented by Mr B Cain of counsel, instructed by Dr W Pickering (patent attorney of F B Rice & Co). The opponent was represented by Dr A Bennett of counsel, instructed by Messrs C Bodkin and J McCann (patent attorneys of Spruson & Ferguson).

The main ground of opposition was one of prior claiming by patent application 600650, and by patent application 657555 (a divisional application currently in opposition, derived from 600650.) The two citations for prior claim are in fact part of a family of patent applications that are related by way of division. The full family is:

At the hearing I raised the issue of whether I ought to have regard to the members of this family other than the two relied upon, using my powers under regulation 5.11. The opponent specifically requested that I do not. However, subsequent to the hearing I was advised by the examiner that the specification and claims of 10074/95 appeared to be identical to the accepted specification and claims of 657555 (and this has not been controverted by either party). Thus, as any findings regarding prior claim by 657555 would prima facie apply equally with respect to 10074/95, I invoked the provisions of reg 5.11 in respect of this application.

Additional grounds argued were that the invention was not a manner of manufacture. Some peripheral matters under s.40, lack of novelty, and lack of inventive step, were also argued.

Proposed amendments

Shortly before the hearing the applicant filed a request under s.104 to amend the specification. The amendments involve small changes in claims 1 and 30, and correct apparent obvious mistakes in the appendency of claims 16 and 31. They otherwise have no bearing on the principal issues in this opposition – and I will not consider them further in this decision, leaving them to be dealt with in the normal manner.

Priority Dates

The present application was filed under the PCT as a convention application claiming priority from three US basic applications:

·   677813 dated 4 Dec 1984,
·   688622 dated 3 Jan 1985, and
·   693258 dated 22 Jan 1985.

Application 600650 was filed on 11 Dec 1984 and claims priority from four US basic applications. Most notably, the specification of 600650 as filed appears to be identical to the specification of the last of those basic applications (675298) which is dated 30 Nov 1984. Consequently any claim in 600650 (or in the divisional application 657555) which is fairly based on the disclosure in 600650 necessarily has a priority date earlier than any priority date that can be accorded a claim in the present application.

The Claims

The objection of prior claim requires a comparison of the invention claimed in the present specification with the claims in the two citations – 600650, and 657555 (and 10074/95 which is identical to 657555). A synopsis of the claims is:

The present application ends with 33 claims of which 10 are independent. These claims are set out in full in Appendix 1.

Application 600650 ends with 56 claims, of which 11 are independent and are set out in Appendix 2. I construed those claims in my earlier decision. I note that:
a)    subsequent to my earlier decision the applicant of 600650 sought to amend those claims, but those amendments have not been allowed;
b)   the decision has been appealed by the opponent; and
c)    the decision has also been also cross-appealed by the applicant.

However, unlike the ground of prior claim by a patent, the ground of opposition of prior claim by an application is not conditional on a determination of validity of the earlier claim. Consequently I consider it appropriate to have regard only to the extant claims – ignoring the proposed amendments, and ignoring my adverse findings under s.40 against several of the claims.

Application 657555 ends with 50 claims, of which 14 are independent and are set out in Appendix 3. 657555 has been opposed, but not yet heard. This hearing ought not pre-empt any findings of substance with respect to that opposition; accordingly I consider it appropriate to proceed on a prima facie basis with respect to (in particular) the issues of priority dates, fair basis or clarity of the claims of that specification.

Application 657555 has been examined. The Commissioner accepted the application on the basis of the present claims. Accordingly I consider there to be a prima facie presumption that the claims comply with section 40 of the Act.

Further, a comparison shows that the specification of 657555 is essentially a photocopy of the specification of 600650. It differs at pp 18 to 22J – where it sets out statements of the invention corresponding to the claims – and at pp 86 to 86M which provide:

Þ new Example 13 and Table XXII, giving a ‘corrected’ gDNA sequence for the clone of Example 5 listed in Table VI; and
Þ new Example 14, giving a ‘subsequent’ carbohydrate analysis of recombinant erythropoietin.

In these circumstances, I consider that there is a prima facie presumption that the claims are entitled to the priority date which flows from 600650 – other than claims that specifically refer to Examples 13 or 14, or Table XXII (ie claims 2, 6, 14, 20, 28, 29, 30, 34, 37, 39, 47, and 48.) [However, as discussed later in these reasons under sequence differences and O-linked glycosylation, I am satisfied that these claims are also prima facie entitled to the priority date which flows from 600650.]

The specification and claims of application 10074/95 are apparently identical to those of its parent application 657555 as accepted.

To conclude this synopsis of the claims, I observe that there are two relatively minor s.40 problems.

Claim 2 refers to ‘a DNA sequence encoding erythropoietin as shown in Table 3’. A similar phrase occurs in claim 3 referring to Table 4. The tables show a sequence that includes both coding and non-coding elements, with the coding region being clearly identified. The question arises as to whether these claims are limited to the whole sequence as shown in these tables, that part of the sequence that is essential for the expression of erythropoietin (ie including the leader region), or just that part of the sequence that codes for erythropoietin. I can find no clear basis for preferring one interpretation over the other, and accordingly these claims are not clear.

Claim 16 is incorrectly appended to itself, while claim 31 is incorrectly appended to claim 29.

The law on prior claiming

The principal ground of objection is that of prior claiming by two patent applications. Historically, while prior claiming by a granted patent was a ground of opposition under both the 1903 Act and the 1952 Act, prior claiming by a patent application was not available as a ground of opposition until it was introduced in the 1952 Act. Subsequently the IPAC report (which lead to the 1990 Act) commented on the objection of prior claim (in para 7.3):

‘This prior claiming approach has proved to be unsatisfactory in practice and, in our opinion, it is too narrow’

and as a result the 1990 Act has replaced the ground of prior claim with the ground of ‘whole of contents’ novelty. However the transitional provisions of the 1990 Act have the effect of maintaining the objection of prior claim for the present application, and excluding any consideration of ‘whole of contents’.

The vast majority of relevant precedent for this objection lies in a series of UK decisions in the period 1960 to 1977. The main decisions dealing with the objection of prior claim are:

Carpmael’s Application (1929) 44 RPC 321
Babcock and Wilcox Ltd’s Application (1952) 69 RPC 224
Commercial Solvent’s Corporation (1954) 71 RPC 143
Merck & Co (Macek’s) Patent [1967] RPC 157
Pittsburgh Glass Co.’s Application [1969] RPC 628
Ethyl Corporation’s (Cook’s) Patent [1970] RPC 227
Esso Research And Engineering Co’s Appln [1971] FSR 118
Westinghouse Electric Corporation (Frost’s) Application [1973] RPC 139
Daikin Kogyo Co Ltd (Shingu’s) Application [1974] RPC 559
B.A.S.F (Distiller’s) Application [1977] FSR 137
Allen & Hanburys (Hayes’) Application [1977] RPC 113

In my view the following passage from Frost’s Application (quoted with approval in Allen & Hanburys) provides a good summary of the principles of the prior claim objection, and why differing tests have been applied by the courts when assessing the objection:

“Now the objection of prior claim is not merely a question of form, but must be looked at as a matter of substance. ..... it is really only the modern statutory equivalent of the requirement of scire facias, that the King should ‘not grant by letters patent one and the self same thing to several persons’. The question which has to be decided in every case under section 14 is therefore whether, as a matter of substance, such a double grant will be made or not.
“From time to time various courts have suggested various tests, none of which are, or can always be, conclusive, since matters of fact, degree, and expert opinion necessarily to a greater or lesser extent affecting the decision are present in every case. Thus the distinct claim test spoken of in Kromschroder’s Patent, the ‘alternative claims’ test spoken of in Merck & Co (Macek’s) Patent [1967] RPC 157 and the ‘selection patent’ test spoken of in Ethyl Corporation’s Patent [1970] RPC 227 (as to which see later) are all attempts by various courts to solve the basic question by applying different tests and analogies. None are entirely satisfactory, conclusive or universally applicable, and it may therefore be useful to repeat what is said on page 231 of the report of the Ethyl case:
“In such circumstances it is unwise, if not impossible, to lay down specific guidelines which will always be of general application, and the conclusion must be reached after a full study of the specifications and other relevant circumstances in each case.”

From this, the principal question to be asked is whether, as a matter of substance, the claims define the same invention. In answering this question the courts have used a range of ‘tests’, which –noting their qualified utility – are as follows:

prior claim cannot be avoided by the incorporation of a feature which was common general knowledge that a person skilled in the art would, without any direction, introduce in a suitable case;

a claim can be notionally rewritten in circumstances where the claim is a shorthand way of expressing a range of alternatives; and

a broad claim which encompasses a narrower later claim will prior claim that later claim unless the additional features in the narrower claim have some significance or importance to the invention - for example:

Þ where the narrower claim is to a different combination; and
Þ where the claim constitutes a selection over the earlier claim (conditional upon the basis of the selection being present in the specification - see I.G. Farbenindustrie A.G.'s Patents (1930) 47 RPC 289 at pp 322 to 323 for the criteria for selection.)

where the earlier claim lies wholly within the scope of the latter claim, or where the areas of the earlier and latter claims overlap in scope, prior claim will usually exist (subject to the issues of selection and combination).

Prior Claim - The PrincipAl Issues

In order for there to be prior claiming, the claims of the present application must either fall within the scope of the claims of the citation, or overlap in scope – otherwise the claim cannot be the subject of the prior claim. In the present case, there was no real argument that the present claims fell outside the scope of one or other of the claims of the citations. Rather the submissions centred on whether the claimed inventions were ‘different’. The principal issues raised by the parties are as follows.

The “invention”

The specification relates to a substance called erythropoietin (often abbreviated as EPO). In my decision on patent application 600650 [hereafter referred to as my earlier decision, and reported at (1996) AIPC ¶91- 231, 33 IPR 557] I outlined the history of the cloning of erythropoietin. I do not need to repeat that history here beyond noting that GI did not succeed in cloning the gene for erythropoietin until about 12 months after Kirin-Amgen had succeeded.

The basis of the inventions of the respective specifications is the DNA coding region for erythropoietin, and there is no suggestion that the parties have identified different coding regions (despite small differences in the exemplified nucleotide sequences). The nature of the present invention is well set out on page 3, where it states:

‘The reported production by others of EPO using genetic engineering techniques had appeared in the trade literature. However, neither an enabling disclosure nor the chemical nature of the product has yet been published. In contrast, the present application provides an enabling disclosure for the mass production of proteins displaying the biological properties of human EPO. It is also possible by such techniques to produce proteins which may chemically differ from authentic human EPO, yet manifest similar (and in some cases improved) properties. For convenience all such proteins displaying the biological properties of human EPO may be referred to hereinafter as EPO whether or not chemically identical thereto.’

I take this paragraph as being indicative that the present invention is broadly concerned with a product that the applicant believed had been produced by someone else – although no-one knew at the time how it was produced. That is, the asserted advance in the art is to provide an enabling disclosure, and not something fundamentally new.

After a coding sequence has been identified, an invention could reside in particular developments of the original sequence. The present specification describes ‘developments’ of the original sequence which are not necessarily disclosed in the citations – such as placing the sequence in particular host cells, using particular promoters, and identifying a specific source of cDNA. However, existence of invention does not automatically follow therefrom. ‘Developments’ which a person skilled in the art would automatically do are in a different category to those that might be characterised as a selection or new combination.

At the hearing a number of differences between the inventions were asserted, which could potentially establish a ‘different’ invention. The major differences are discussed in the following paragraphs.

Sequence differences

There was considerable debate about the significance of errors and omissions in the DNA sequence set out in 600650. It was common ground that there were no errors in the part of the sequence which codes for the protein. However the 600650 sequence includes an intron region of over 100 nucleotides where the nucleotides are unidentified; and there are otherwise a number of differences between the sequences outside the protein coding region.

The evidence of the parties does not suggest that the genes identified in the respective specifications were different genes. Thus the method used in the earlier specification will produce the same gene as in the present specification – irrespective of whether or not the corresponding DNA sequences said to represent the gene are the same. That is, a different invention does not arise merely because the sequences as enumerated are different.

The applicant placed importance on their identification of the intron sequences. However it is apparent that both parties had isolated the gene with the introns; the only difference is that the applicant had fully sequenced the introns. However this further characterisation of the gene does not alter the nature of the gene, and therefore does not change the invention. Consequently the applicant has not established a basis for there being a different invention by reason of differences in the DNA sequences. I also observe that the applicant has not demonstrated (beyond mere speculation) any purpose that is served by these introns.

Finally, there is no evidence that the differences in the sequences would have unduly hindered the isolation of the erythropoietin gene such that the specification of 600650 was not enabling. As a consequence, new Table XII in 657555 merely enumerates further technical details of what was inevitably produced in 600650 (see, for example, Merck v Sankyo 23 IPR 415, and Farbwerke Hoechst AG Vormals Meister Lucius & Bruning v Commissioner, [1971] 124 CLR 654). Thus I consider the claims of 657555 which refer to new Table XXII are nevertheless entitled to a priority date flowing from 600650. As a result, I am prima facie satisfied that all the claims of 657555 referring to Table XXII are entitled to a priority date flowing from 600650.

cDNA

At the hearing there was considerable discussion concerning what was meant by the term cDNA, with the applicant placing great importance on it.

In my former decision I concluded that the fundamental difference between a DNA sequence and a cDNA sequence is the presence/absence of introns. GI argued that the term cDNA, as used in their specification, refers to a complete reverse transcript of mRNA [and therefore includes nucleotides coding for an amino acid leader sequence, as well as nucleotides for the flanking regions outside the amino acid coding region] having specific end-points in the flanking regions – referring to Kirin-Amgen/Erythropoietin [1995] EPOR 629 [the decision of the European Patent Office Technical Board of Appeal on the European patent corresponding to AU600650].

The scope of the term cDNA is properly addressed by considering the manner in which the term is used in the present specification. Relevantly, on page 16 it states:

“EPO/cDNA as used herein includes the mature EPO/cDNA gene preceded by an ATG codon and EPO/cDNA coding for allelic variations of EPO protein. One allele is illustrated in Tables 2 and 3. The EPO protein includes the 1-methionine derivatives of EPO protein (Met-EPO) and allelic variations of EPO protein. The mature EPO protein illustrated by the sequence in table 2 begins with the sequence Ala.Pro.Pro.Arg... the beginning of which is depicted by the number “1” in table 2. The Met-EPO would begin with the sequence Met.Ala.Pro.Pro.Arg...”

The sequence Ala.Pro.Pro.Arg is the commencement of the EPO protein, and the reference to ‘mature’ is a reference to the protein coding region without the leader sequence. Thus this definition of cDNA does not include either a leader region or a flanking region; it is consistent with cDNA embracing solely the protein coding region without any introns.

Further, claim 16 of the present specification (dependent upon claim 15) claims a cDNA sequence ‘further comprising’ a 27 amino acid leader sequence. On its plain meaning, I take claim 16 as providing an additional length of DNA to the cDNA specified in claim 15. That is, whilst the term cDNA used in the claims is, at times, clearly intended to include a leader region, the term does not require the presence of either a leader sequence or flanking regions.

I am therefore of the view that the present specification uses the term cDNA simply to refer to a DNA sequence containing a protein coding region uninterrupted by introns – the term does not imply the presence or absence of either leader regions or flanking regions. In particular, there is nothing in the specification that limits the term cDNA to mean DNA that is a one-to-one complement of an expressed mRNA. In my view the meaning cDNA as used in the present specification is not distinguished from the meaning of the term as I found it used in 600650.

GI further argue that cDNA necessarily contains flanking regions. They argue that KA did not characterise these flanking regions; that these flanking regions are very important as they likely affect the stability of the mRNA and expression rates, and (it was suggested) might even effect the glycosylation processes; that their flanking region was different to Kirin-Amgen; and that they therefore had a different invention.

The need for a flanking region is/was well understood in the art – in the transcription process, the flanking region is where the ribosome initially attaches itself to the mRNA. It is also known that the flanking regions correspond to the similarly located nucleotides in the genomic DNA. In these circumstances I am lead to the general view that the person skilled in the art would know that flanking regions from the gDNA were required. Therefore the mere existence of particular flanking regions does not constitute a different invention [unless, of course, a selection is involved in the choice of flanking regions]. I cannot find anything in the present specification or the evidence which identifies the significance of the particular flanking regions (beyond their presence in the clones). Indeed, the lack of importance of the start location of the flanking regions in this case is highlighted at page 21 of the present specification, where it states:

“A schematic representation of five exons coding for EPO mRNAs is shown in Figure 4. The precise 5-prime boundary of exon 1 is presently unknown.”

Exon 1 is the exon that includes the flanking region preceding the coding region for erythropoietin. This statement effectively means that the specification does not (and cannot) identify the location of the start of the initial flanking region. In this context it is also significant that the sequences listed in tables 3, 4, 5, 6, and 7 have flanking regions which are of different length.

Because the specification does not demonstrate any importance to the choice of particular flanking regions, I conclude that the presence or absence of a flanking region does not alter the nature of the present invention – in particular, the criteria for selection do not exist in the context of specifying the details of the flanking regions.

cDNA given gDNA

An issue arises with regard to whether 600650 relevantly discloses a cDNA. In 600650 it is expressly stated that KA had not obtained mRNA from a natural human source. GI argue that this is an admission that KA had not disclosed a true cDNA. I note however that 600650 does purport to show a cDNA, particularly in the sense that it identifies the intron regions. It also refers (on page 49) to the sequencing of a cDNA sequence clone prepared from a mRNA isolated from COS-1 cells transformed with the human genomic DNA sequence in example 7 – that is, whilst they had not obtained mRNA from a natural human source, they had obtained it via cellular expression from a genomic clone.

Further, given a gDNA sequence, the obtaining of a cDNA sequence is routine. It merely requires insertion of the gDNA sequence into a eucaryotic cell, isolating mRNA expressed therefrom, and performing reverse transcription of the mRNA to obtain the cDNA. That is, given gDNA, cDNA is deduced by routine procedures normally not involving any invention over and above the derivation of the gDNA. Accordingly, in the absence of some identified problem in deriving the cDNA from the gDNA, I consider that the cDNA corresponding to a gDNA sequence is in fact the same invention as the gDNA.

Fetal Liver

While 600650 discloses the isolation of a cDNA clone, it explicitly does not contemplate screening a cDNA library as no relevant enriched source of erythropoietin was known – as a result, they isolated a gDNA clone from which they obtained a cDNA clone. Accordingly it cannot be said that any claim in 600650 (or 657555) can explicitly claim a step of isolation from a human fetal liver cDNA library. Nor, to the extent that any relevant claim may use generalities, can any claim in 600650 or 657555 be considered as being a shorthand way of expressing a range of alternatives of which the use of a cDNA library from fetal liver is one.

Additionally, the evidence includes the paper Regulation of Fetal Liver Erythropoiesis Journal of Steroid Biochemistry (1977) page 423. This paper suggests human fetal liver as an enriched source of erythropoietin. However there is nothing to suggest that this was part of the common general knowledge such that it is properly included in the claim in the manner of Babcock and Wilcox Ltd’s Application (supra). If it was truly common general knowledge, it would seem highly likely that KA would have used this source to produce a cDNA library. On the other hand, the use of fetal liver produced a cDNA clone when other workers were unable to do so using whatever sources were available . Thus the use of a fetal liver library meets the selection criteria.

Consequently, I consider that a claim to a method of isolating the erythropoietin gene using human fetal liver, is directed to a different invention to that disclosed in 600650.

O-Linked Glycosylation

The specification of 600650 briefly describes the results of a carbohydrate analysis of the erythropoietin, including a value for N-acetylglucosamine of zero (whereas the present specification derives a non-zero value). The present specification draws the conclusion that this means that there is no O-linked glycosylation in 600650, and hence the products are different. However I am not satisfied that this is sufficient to establish that the erythropoietin described in 600650 was not in fact O-linked. As far as I can ascertain from the respective specifications, the cellular expression is from the same CHO cell-line, and therefore there must be an overwhelming presumption that the form of glycosylation obtained is the same in both specifications – irrespective of what form of glycosylation is asserted (or inferred) to be present in the specifications. It is also noteworthy that the measurement given in the present specification of the value for N-acetylglucosamine is 0.1, on a scale where the significant unit is 0.1 – that is, the measurement (as presented) may be close to the limit of detection. Interestingly, Kirin-Amgen assert that the tests results referred to in 600650 were done in haste, and were subsequently found to be wrong. In all, I do not think that the measurements presented in the specifications are such as to displace the presumption that the glycosylation is the same. Further, there was no evidence from either party directly comparing the products. Nor was there any suggestion that the errors would have unduly hindered the isolation of the product; the errors merely relate to the description of the product inevitably produced.

The claims of both the present application, and 657555, set out details of the glycosylation in some detail. However, in both cases those details are simply setting out the inherent glycosylation obtained from expression by CHO cells. The word ‘characterised’ does not define a different invention – it merely provides further elaboration of the same invention.

As an aside, I observe that the corrected glycosylation details in 657555 are inherent in 600650, and therefore the claims of 657555 that are ‘characterised’ by the corrected O-linked glycosylation are entitled to a priority date flowing from 600650

Promoters and Cell Lines, etc

Although not argued at the hearing, many of the claims are potentially distinguished from the citations by differences in either the promoter or vector used, the particular host cell, or the culture conditions. In the art, it is well known that a wide range of promoters, vectors, cell lines, and culture conditions can, and would be, used in suitable cases. In my view, for such features to give rise to a different invention, it must be shown that either a selection is involved, or that claims characterised by these features fall outside the scope of relevant claims in the citations. I observe that the use of a specific promoter, cell line, etc in a later specification for the same purpose as exemplified in the earlier specification could not be said to produce a surprising result – and therefore could not give rise to a selection. Otherwise, there is no relevant evidence to establish either condition, and therefore such features do not give rise to a different invention.

Method vs substance

A final point regarding the law of prior claim concerns the issue of whether a claim to a substance prior claims a method claim. Specifically, none of the claims of 600650 are directed per se to a method for the production of erythropoietin, whereas there are claims to methods in the present claims. Blanco White (4th edition) at para 4-304 states that:

‘The distinction between a claim to an article and a claim to a process of making it or a process employing it or to that article when made by a particular process is not in itself sufficient to prevent prior claiming.’

but adds:

‘This paragraph is based entirely on [Patent Appeal Tribunal] decisions; the Court of Appeal, following its affirmation of Kromschroder’s Patent [1960] RPC 75 (CA) in Daikin Kogyo’s Patent might well take a directly contrary view.’

In my view, and having regard to the dictionary definition of exploit in the 1990 Act (which essentially encapsulates the patent rights under the 1952 Act), a claim to a substance which requires the steps set out in a claim to a method of producing that substance, prior claims the method claim. Conversely, where a substance can be produced by methods other than the claimed method, I do not think that a claim to the method would be prior claimed by the claim to the substance per se.

Decision on Prior Claim

As I stated earlier, in order for there to be prior claiming, the claims of the present application must either fall within the scope of the claims of the citation, or overlap in scope – otherwise the claim cannot be the subject of the prior claim. In the present case, there was no real argument that the present claims fell outside the scope of one or other of the claims of the citations. I am satisfied that all the claims of the present application fall within the scope of one or more claims of one or other of the citations.

That being the case, the consideration of prior claim entails a consideration of whether the invention claimed in the present application constitutes the same or a different invention compared with 600650 or 657555 [such as would be the case if a selection or a new combination was involved]. My conclusions are set out in the table of Appendix 4. In this table I have focussed primarily upon the claims that explicitly are closest to the claims of the present application. Thus where I conclude that a claim is prior claimed by a dependent claim in a citation, it should be understood that I consider that prior claim by the parent claims also exists.

As set out in Appendix 4, I conclude that all the claims of the present application are the subject of a prior claim, with the sole exception of claim 1. In my view, the basic invention of all three specifications resides in the identification of the same gene encoding erythropoietin. All the claims of 621535 are encompassed within the claims of one or other of 600650 or 657555. To the extent that features in the present claims are not specifically defined in the claims of 600650 or 657555, I observe that they are generally matters of common knowledge that may be expected to be used in the art – and there is no evidence that there is any basis for selection founded upon their presence in the claim. The sole exception to this is claim 1, where the use of fetal liver as a source of mRNA to isolate erythropoietin is sufficient to establish selection.

Manner of Manufacture

To be patentable, an invention must be in respect of a manner of new manufacture within the meaning of s.6 of the Statute of Monopolies. The Statute of Monopolies of 1623 declared all monopolies "... for the sale, buying, selling, making, working, or using of any thing within this realm ..." to be contrary to law and utterly of no effect with certain exceptions. Section 6 relates to patents for inventions, and provides:

‘6. Provided also, and it be declared and enacted, That any declaration before mentioned shall not extend to any letters patent and grants of privilege for the term of fourteen years or under, hereafter to be made of the sole working or making of any manner of new manufactures within this realm, to the true and first inventor and inventors of such manufactures, which others at the time of making such letters patent and grants shall not use, so as also they be not contrary to the law or mischievous to the State, by raising prices of commodities at home, or hurt of trade, or generally inconvenient; the said fourteen years to be accounted from the date of the first letters patents or grant of such privilege hereafter to be made, but that the same shall be of such force as they should be if this Act had never been made, and of none other.’

The question that the opponent raises in the present case is whether the objection of manner of new manufacture is to be assessed in the context of public knowledge, or in the context of all knowledge. On the submissions of Dr Bennett, it is appropriate to have regard to all knowledge – and in particular all knowledge within the possession of the Commissioner at the relevant priority date. Thus, in the present case Dr Bennett argues that the Commissioner had possession of the knowledge contained in the specification of 600650 before the priority date of the present application; that the present application contains nothing new over 600650, is therefore not a manner of new manufacture, and can now be refused for that reason.

This submission is ingenious. But if true, it strikes me as odd that the UK courts persisted with their line of problematic decisions on prior claim if the relevant wrong could have been dealt with under the heading of manner of new manufacture. Similarly, it is odd that both the UK and Australian parliaments have seen fit to eliminate the prior claim objection by replacing it with a ‘whole of contents’ novelty objection – if the relevant wrong was within the scope of the objection of manner of new manufacture. Similarly, if this submission were true, the Commissioner’s entire holding of unpublished provisional specifications would be available to invalidate patents – a situation that has never been contemplated. And if manner of manufacture were to be assessed against private knowledge, inventors would have to file patent applications on the very same day as they conceive their invention so as to avoid self-anticipation! Against this, it is noteworthy that a review of cases dealing with whether an invention is a manner of manufacture (eg see 1-201 et seq of Patents for Inventions, fourth edition, Blanco White) readily shows that the issue of manner of manufacture has always been assessed in the context of public knowledge. Thus, to the extent that assessment of manner of manufacture requires assessment against some form of knowledge, I consider that such knowledge must be at least publicly known.

Accordingly I do not accept Dr Bennett’s arguments, and find that the objection of manner of new manufacture has not been made out.

Novelty, and Obviousness

In my earlier decision I found the claims of 600650 to be both novel and non-obvious. The priority date of the present application is some 12 months after the priority date of 600650. Given the closeness of the respective inventions, I am of the view that my reasoning and conclusions as regards novelty and obviousness that I reached in my earlier decision applies equally to the present application – except to the extent that there may have been relevant publications in that intervening period, or (in the context of obviousness) some other factor arising in that period that would lead to a different conclusion.

With regard to novelty, it is apparent that the applicant of 600650 sought not to publicise their invention; indeed I understand that the DNA sequence of erythropoietin was first published in the scientific literature by the present applicant. The evidence does not show any relevant publications in the intervening period. There is therefore no basis to come to a different conclusion on novelty.

With regard to obviousness, the evidence suggests that subsequent to Kirin-Amgen succeeding in cloning erythropoietin, there were rumours to that effect; and those rumours may have given some indication of the path Kirin-Amgen took to succeed. However, whether or not such rumours existed, and whether or not such rumours may have affected the ability of the present applicant to succeed in cloning the invention, there is no evidence that such rumours were present in Australia prior to the present priority date, let alone accepted in Australia as a basis for further action. Consequently, as the objection of obviousness is dependent upon the common general knowledge in Australia at the relevant date, I conclude that my finding that the invention claimed in 600650 was not obvious applies equally to the present application.

Consequences of the finding of Prior Claim by an application

I have found that the majority of claims are subject to the ground of objection of being prior claimed by the claims of a patent application. The opponent argued that the present application should not proceed to grant until any application likely to lead to a prior claim situation had proceeded to grant (or lapsed, refused, withdrawn). The applicant, of course, sought to have their application proceed to grant as soon as possible.

Subsection 60(4) of the Patents Act 1952 provides:

‘The grant of a patent shall not be refused on the ground specified in paragraph 59(1)(c) if a patent has not been sealed on the application mentioned in that paragraph.’

It is noteworthy that while the grounds of opposition include prior claiming by an application, the grounds of revocation (s.100 of the 1952 Act) are limited to prior claim by a patent. This is a reflection of the real basis of the objection of prior claiming. The ‘wrong’ that is being addressed is the grant of more than one patent for the self same thing. That ‘wrong’ does not exist in the absence of the earlier claim being the subject of a valid granted patent that is in force. The ground of objection of s.59(1)(c) may therefore be seen as providing no more than an administrative mechanism to avoid such wrongs from occurring when a later application is ready for grant before a patent has been granted on the earlier application; unlike the other grounds of opposition, this ground is not per se a ground of invalidity.

Additionally I note the provisions of s.64(1) of the 1990 Act [corresponding to s.67(3) of the 1952 Act] which provides:

‘Subject to this section, where there are 2 or more applications for patents for identical, or substantially identical, inventions, the granting of a patent on one of those applications does not prevent the granting of a patent on any of the other applications.’

which makes it quite clear inter alia that the grant of a patent on an application said to be prior claimed by an earlier application, has no bearing on whether a patent should ultimately be granted on the earlier application.

In my view, the effect of subsections 59(1)(c) and 60(4) is to provide the Commissioner with a broad discretion regarding the grant of a patent in the face of an objection of prior claim by a claim of an earlier application. In the decision of General Tyre’s Appln [1967] FSR 353, the hearing officer in the UK Patent Office endeavoured to set some relevant guidelines. The Commissioner’s decisions in Herchel Smith v. Roussel Uclaf (1973) 43 AOJP 5017, Herchel Smith v. Roussel Uclaf (1974) 44 AOJP 1997, and Les Laboratories Francais v Herchel Smith (1975) 45 AOJP 2776 – to the extent that they have been reported – are consistent with those guidelines. However the circumstances of the present case involve some different considerations.

I first observe that neither 600650 or 657555 can presently proceed to grant because of actions taken by the present applicant – in the case of 600650 by their appeal against my earlier decision, and for 657555 by their opposition. For two reasons, I do not consider it appropriate for the present application to proceed to grant in the face of the ground of prior claim by either of those applications. Firstly, both these applications have received consideration by the Commissioner [for 600650, by my earlier decision; for 657555, the Commissioner’s examination and the acceptance of the application], and are actively being pursued by the applicant. There is thus a prima facie reason to believe that any grant of the present application in the face of the prior claim objection, would ultimately be invalidated by patents granted on 600650 and 657555 – a situation that is not in the public interest. Secondly, it is the actions of the present applicant which are preventing (quite lawfully) the grant of patents on those applications; it would be incongruous for the present application to proceed to grant merely on the basis that actions by the applicant had resulted in the delay of grant of patents on the citations.

I secondly observe the potential for there to be an ongoing series of divisional applications – each providing a basis for establishing the ground of objection of prior claim by a patent application. As the objection of prior claim by an application is not dependent upon whether the citation has been examined, it is readily apparent that divisional applications could be used to frustrate the grant of a patent – and the fact that the specification and claims of 10074/95 are prima facie the same as 657555 is clearly indicative of that potential. I do not think that the provisions relating to prior claim by an application were ever intended to leave an applicant subject to the whims of others who file a continuing series of divisional applications. Rather, in such circumstance I think the applicant is properly entitled to demand the grant of a patent – despite the existence of divisional applications that may be said to constitute a prior claim.

The opponent sought further justification for their argument that the application should not proceed to grant by reference to a 1515 Act under Henry VIII. This Act, which I have reproduced in Appendix 5, is the historical basis of the prior claim objection (and interestingly pre-dates the Statute of Monopolies by over 100 years.) The opponent sought to rely on the two references in this Act to patents ‘hereafter to be granted’ as preventing a patent from being granted so long as there was a possibility that a patent would be granted in the future that would prior claim it. I disagree. I think these references do no more than express the intention that the Act would void patents granted in the future, as well as patents already granted. It does not set an environment where the grant of a patent might be deferred because of the possibility of the grant of another patent – which is anything but surprising given that prior to about 1800 patents were granted on the basis of a title alone, and claims were not compulsory before 1883.

Accordingly (and in the absence of amendments to any of the applications having the effect of removing the objection of prior claim by 600650 and 657555), I consider that the present application should not proceed to grant until both 600650 and 657555 have either proceeded to grant (in which event the Commissioner will need to consider whether the ground of prior claim by a patent has been made out), or have lapsed, been refused, or withdrawn. On the other hand, I do not consider that any other application deriving priority from 600650 by way of divisional applications should be a bar to the present application proceeding to grant. I consider that any such divisional application should only be considered by the Commissioner if and when a patent is granted on it – and then only if the ground of invalidity of prior claim by valid claim of that patent can be made out.

Costs

In actions before the Commissioner, costs usually follow the event. I have found all but one of the claims the subject of prior claim. I therefore consider the opponent has succeeded in its opposition, and I award costs against the applicant.

Conclusion

I have found that:

all claims except claim 1 are the subject of prior claim by patent applications 600650, 657555, and 10074/95; and

claims 2, 16, and 31 lack clarity.

With regard to the further prosecution of this case, I direct as follows:

the present application is not to proceed to grant in its present form until both 600650 and 657555 have either proceeded to grant, or have lapsed, been refused, or withdrawn;

patent application 10074/95, and any other applications deriving priority from patent application 600650, shall not be a barrier to the present application proceeding to grant – unless and until a patent is granted on any such application;

the applicant has 90 days from the date of grant of a patent on one or other of 600650 and 657555 to either:

Þ request amendments to avoid the objection of prior claim by a valid claim of a patent;
Þ seek directions as to how the application should proceed; or
Þ request to be further heard.

the applicant has 60 days from the date of lapsing, refusal or withdrawal of both 600650 and 657555 to amend the specification to remove the section 40 problems; and

the applicant is otherwise at liberty to propose amendments to the present application.

D Herald
Deputy Commissioner of Patents

Patent attorneys for the applicant : F B Rice & Co, Balmain
Patent attorneys for the opponent : Spruson & Ferguson, Sydney

APPENDIX 1

The Claims of 621535

A method of producing a human cDNA clone which expresses biologically active erythropoietin comprising:
(a)digesting purified erythropoietin protein with trypsin;
(b)making a pool of oligonucleotide probes based on the amino acid sequence of the tryptic fragments produced in step (a);
(c)screening a human genomic DNA library with the oligonucleotide probes of step (b);
(d)selecting clones that hybridize to the probes and sequencing the clones to determine whether they are erythropoietin clones;
(e)identifying an erythropoietin clone from step (d);
(f)using the clone from step (e) to screen a cDNA library prepared from human fetal liver; and
(g)selecting an erythropoietin clone from the fetal liver cDNA library of step (f).

A method for the production of erythropoietin comprising culturing in a suitable medium host cells transformed with a DNA sequence encoding erythropoietin as shown in Table 3 operatively linked to an expression control sequence, and separating the erythropoietin so produced from the cells and the medium.

A method for the production of erythropoietin comprising culturing in a suitable medium eucaryotic host cells transformed with a DNA sequence encoding erythropoietin as shown in Table 4 operatively linked to an expression control sequence, and separating the erythropoietin so produced from the cells and the medium.

A method of claims 2 or 3 wherein the host cells are mammalian cells.

A method of claim 4 wherein the mammalian cells are 3T3 cells, as hereinbefore defined.

A method of claim 4 wherein the mammalian cells are Chinese hamster ovary (CHO) cells.

A method of claim 4 wherein said DNA sequence is contained in a vector also containing bovine papilloma virus DNA.

A pharmaceutical composition comprising a therapeutically effective amount of erythropoietin produced by the method of claims 2-7 in a pharmaceutically acceptable vehicle.

A recombinant DNA plasmid vector containing the cDNA clone, lambda-HEPOFL13, as hereinbefore defined.

A mammalian cell line transformed with the transfer vector of claim 9.

The cell line of claim 10 wherein said mammalian cells are 3T3, C127 or CHO cells, as hereinbefore described.

A recombinant DNA vector comprising a genomic DNA clone encoding erythropoietin and having a nucleotide sequence as shown in Table 4.

A mammalian cell line transformed with the vector of claim 12.

The cell line of claim 13 wherein said mammalian cells are CHO cells.

A cDNA molecule comprising a DNA sequence encoding erythropoietin having the amino acid sequence 1-166 substantially as shown in Table 3.

The cDNA molecule of claim 16 further comprising a DNA sequence encoding the amino acid leader sequence MET GLY......LEU GLY substantially as illustrated in Table 3.

A recombinant DNA vector comprising a heterologous promoter and the cDNA sequence of claim 15 or 16.

A mammalian cell line transformed with the vector of claim 17.

The cell line of claim 18 wherein said mammalian cells are 3T3, C127 or CHO cells, as hereinbefore defined.

A mammalian cell transformed with bovine papilloma virus DNA and a DNA sequence coding for EPO, as hereinbefore defined.

The cell of claim 20 wherein said cell is a C127 or 3T3 cell, as hereinbefore defined.

A DNA molecule comprising the DNA sequence of Table 4.

The cell of claim 21 wherein said EPO DNA is under transcriptional control of a mouse metallothionein promoter.

The cell of claim 21 wherein said cell contains a plasmid comprising DNA from pdBPV-MMTneo (342-12) as hereinbefore defined.

Erythropoietin produced by the method of claims 3 or 4 which is further characterised by the presence of O-linked glycosylation.

A method according to either claim 2 or 3 wherein the culture medium contains fetal serum.

A method of claim 26 wherein the host cells are mammalian cells.

A method of claim 27 wherein the mammalian host cells are COS, CHO, C127 or 3T3 cells.

A method for the production of a pharmaceutical composition of human erythropoietin comprising:
(a)culturing in a suitable medium eucaryotic host cells transformed with a DNA sequence encoding human erythropoietin selected from the group consisting of: the DNA of table 3; the DNA of table 4; and the DNA of Table 4 comprising nucleotide “GGTC” fifty nucleotides upstream of the ATG codon encoding -27 Met through nucleotides TGA following the AGA codon encoding the 166 Arg and the DNA of Table 4 comprising the ATG codon encoding -27 Met through nucleotides TGA following the AGA codon encoding the 166 Arg, said sequences operatively linked to an expression control sequence;
(b)separating the human erythropoietin so produced from the cells and the medium; and
(c)formulating said erythropoietin in conjunction with a pharmaceutically acceptable vehicle.

Recombinant human erythropoietin characterised by the presence of O-linked glycosilation, obtainable by the steps of
(a)culturing in a suitable medium CHO cells containing a DNA sequence encoding human erythropoietin said DNA sequence operatively linked to an expression control sequence and
(b)recovering and separating the EPO from the cells and the medium.

Recombinant human erythropoietin as claimed in claim 29, characterised by a glycosilation pattern comprising fucose.

Recombinant human erythropoietin as claimed in claim 30, characterised by a glycosilation pattern comprising relative molar levels of hexoses to N-acetylglucosamine (Nacglc) of 1.4 : 1, specifically galactose : Nacglc = 0.9 : 1 and mannose : Nacglc = 0.5 : 1.

Recombinant human erythropoietin as claimed in claim 30 or 31, characterised by the presence of N-acetylgalactosamine.

Appendix 2

The Independent claims of 600650

Application 600650 ends with 56 claims, of which 11 are independent claims. The independent claims are:

A purified and isolated polypeptide having the primary structural conformation and one or more of the biological properties of naturally-occurring erythropoietin and characterized by being the product of procaryotic or eucaryotic expression of an exogenous DNA sequence.

A purified and isolated DNA sequence encoding erythropoietin, said DNA sequence selected from the group consisting of:

(a)The DNA sequences set out in Tables 5 and 6 or their complementary strands; and

(b)DNA sequences which hybridize under stringent conditions to the DNA sequences defined in (a).

A purified or isolated DNA sequence consisting essentially of a DNA sequence encoding human erythropoietin.

A purified and isolated DNA sequence consisting essentially of a DNA sequence encoding monkey erythropoietin.

A DNA sequence coding for a polypeptide analogue of naturally-occurring erythropoietin.

A DNA sequence coding for [Phe15]hEPO, [Phe49]hEPO, [Phe145]hEPO, [His7]hEPO, [ASN2 des-Pro2 through Ile6]hEPO, [des-Thr163 through Arg166]hEPO or [D27-55]hEPO.

A non-naturally occurring glycoprotein product of the expression in a non-human eucaryotic host cell of an exogenous sequence consisting essentially of a DNA sequence encoding human erythropoietin said product possessing the in vivo biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells and having an average carbohydrate composition which differs from that of naturally occurring human erythropoietin .

A synthetic polypeptide having the amino acid sequence as set forth in Table V and having one or more of the in vivo or in vitro biological activities of naturally occurring monkey erythropoietin.

A synthetic polypeptide having the amino acid sequence as set forth in Table VI, other than a sequence of residues entirely within the sequence numbered 1 through 20, and having a biological property of naturally-occurring human erythropoietin.

An antibody substance characterized by immunoreactivity with erythropoietin and with a synthetic polypeptide having a primary structural conformation substantially duplicative of a continuous sequence of amino acid residues extant in a naturally-occurring erythropoietin except for any polypeptide comprising a sequence of amino acid residues entirely comprehended within sequences,

A-P-P-R-L-I-C-D-S-R-V-L-E-R-Y-L-L-E-A-K

A purified and isolated DNA sequence as set out in Table V or VI or the complementary strand of such a sequence.

Appendix 3

The Independent Claims of 657555

Application 657555 ends with 50 claims, of which 14 are independent claims. The independent claims are:

A method for the production of erythropoietin comprising culturing in a suitable medium host cells transformed with a DNA sequence encoding erythropoietin operatively linked to an expression control sequence, and separating the erythropoietin so produced from the cells and the medium.

A method for the production of erythropoietin comprising culturing in a suitable medium eucaryotic host cells transformed with a DNA sequence encoding erythropoietin as shown in Table XXII operatively linked to an expression control sequence, and separating the erythropoietin so produced from the cells and the medium.

A recombinant DNA vector comprising a genomic DNA clone encoding erythropoietin having a nucleotide sequence as shown in table XXII.

A DNA molecule comprising a DNA sequence encoding erythropoietin having the amino acid sequence 1 to 166 shown in Table VI.

A DNA molecule comprising the DNA sequence of Table XXII.

A method for the production of a pharmaceutical composition of human erythropoietin comprising:
(a)       culturing in a suitable medium eucaryotic host cells transformed with a DNA sequence encoding human erythropoietin, said sequence operatively linked to an expression control sequence;
(b)       separating the human erythropoietin so produced from the cells and the medium; and
(c)       formulating said erythropoietin in conjunction with a pharmaceutically acceptable vehicle.

Recombinant human erythropoietin characterised by the presence of O-linked glycosylation, obtainable by the steps of
(a)culturing in a suitable medium Chinese hamster ovary (CHO) cells containing a DNA sequence encoding human erythropoietin said DNA sequence operatively linked to an expression control sequence and
(b)recovering and separating the EPO from the cells and the medium.

A method for the production of erythropoietin comprising culturing in a suitable medium host cells transformed with a DNA vector having a DNA sequence encoding erythropoietin operatively linked to an expression control sequence whereby said cells produce erythropoietin; and
separating the erythropoietin so produced from the cells and the medium.

A method for the production of erythropoietin comprising culturing in a suitable medium eukaryotic host cells transformed with a DNA vector having a genomic DNA sequence encoding erythropoietin operatively linked to an expression control sequence whereby said cells produce erythropoietin; and
separating the erythropoietin so produced from the cells and the medium.

A method for the production of human erythropoietin comprising;
growing, under suitable nutrient conditions, procaryotic or eucaryotic host cells transformed or transfected with a biologically functional DNA vector having a sequence selected from the group consisting of the DNA sequence set out in Table XXII or its complimentary strand and a DNA sequence which hybridizes under stringent conditions to the DNA sequence set out in Table XXII, and separating the erythropoietin so produced from the cells and the medium.

A recombinant DNA vector comprising a genomic DNA clone encoding erythropoietin having an amino acid sequence substantially as shown in table VI or Table XXII.

A DNA molecule comprising a DNA sequence encoding erythropoietin having the amino acid sequence 1 to 166 shown in Table XXII.

A method for the production of a pharmaceutical composition of human erythropoietin comprising:
(a)culturing in a suitable medium eucaryotic host cells transformed with a DNA vector having a DNA sequence encoding human erythropoietin operatively linked to an expression control sequence whereby said cells produce erythropoietin, wherein said human erythropoietin has an amino acid sequence substantially as shown in Table VI or Table XXII;
(b)separating the human erythropoietin so produced from the cells and the medium; and
(c)formulating said erythropoietin in conjunction with a pharmaceutically acceptable carrier, diluent and/or adjuvant.

A method of producing a human cDNA clone which expresses biologically active erythropoietin comprising:
(a)digesting purified erythropoietin protein with trypsin;
(b)making a pool of oligonucleotide probes based on the amino acid sequence of the tryptic fragments produced in step (a);
(c)screening a human genomic DNA library with the oligonucleotide probes of step (b);
(d)selecting clones that hybridize to the probes and sequencing the clones to determine whether they are erythropoietin clones; and
(e)identifying an erythropoietin clone from step (d).

Appendix 4

Prior Claim - detailed comparison of the claims

Claim	Prior Claim?	600650	657555	Comments
1	No	—	—	· 600650 asserts that a source of enriched mRNA not known – hence screened a gDNA library. As discussed above, the use of fetal liver is sufficient for selection. Thus although within the scope of the earlier claims, not the same invention.
2	Yes	1, 47	1, 2, 25	· Citations disclose the same coding region. · cDNA encompassed within the scope of DNA sequence; cDNA not a different invention, given gDNA · No identified importance for any differences outside the coding region – and therefore no selection. · Claim 1 of 600650 entails the features of the method claimed, and therefore is the same invention.
3	Yes	1, 47	1, 2, 27	· As for claim 2. · No identified importance associated with sequence differences. · Claim 1 of 600650 can properly be notionally rewritten to refer to eucaryotic cells.
4	Yes	1, 47	3	· As for claims 2 & 3. · Claim 1 of 600650 requires cellular expression, and encompasses mammalian cells. Because mammalian cells used in the examples of 600650, there is no surprising result; thus selection criteria not met.
5	Yes	1, 47	3	· As for claim 4. 3T3 cells are encompassed by the term ‘mammalian cells’, and no advantages are indicated in their use. Selection criteria not met.
6	Yes	1, 47	4	· CHO cells specifically claimed in 657555. · 600650, as for claim 5. Even though there is an identified advantage in the use of CHO cells [glycosylation], those cells were used in 600650. Thus selection criteria not satisfied.
7	Yes	1, 47	4	· As for claim 4. · Although neither 600650 nor 657555 claim specific promoters, they are inherent in the claims involving expression systems. · The choice of a particular promoter (ie bovine papilloma virus) involves no surprising advantages – thus selection criteria not met.
8	Yes	52	5	· Same as claim 5 of 657555. · The product of the invention in all specifications is intended for pharmaceutical use. The presence of the substance in an effective amount, and in an appropriate vehicle, would be automatically understood.
9	Yes	20 (via claim 17)	—	· closest claim in 657555 is claim 11. From the evidence, and the specification of 621535, it is not apparent that l-HEPOFL13 inherently has a promoter. Therefore I cannot conclude that the claim falls within the scope of claim 11, and therefore prior claim has not been established. Additionally, there is no basis to notionally rewrite claim 9 as having a promoter. · The next closest claim of 657555 is claim 34. But this is limited to genomic DNA, which does not encompass l-HEPOFL13. Therefore no prior claim. · claim 20 of 600650 encompasses any recombinant DNA vector, including those containing cDNA (which is not a different invention, given gDNA); further, there are no identified advantages for the particular plasmid vector l-HEPOFL13 - hence selection criteria not met.
10	Yes	21	—	· As for claim 9. · Mammalian cells are encompassed within the scope of eucaryotic cell, and exemplified in 600650. Thus selection criteria not met.
11	Yes	21	—	· As for claim 10. · 3T3, C127 are encompassed within mammalian cells. The specification does not indicate any particular advantages in their use. Thus selection criteria not met. · CHO cells are encompassed within mammalian cells. While some advantage is indicated [glycosylation], they are exemplified in 600650. Thus selection criteria not met.
12	Yes	20	6	· The specific vectors defined in claim 20 are recombinant DNA vectors. · The protein coding region of the sequence in Table 4 is the same as the protein coding region in 600650. There are no advantages identified with the specific sequence of Table 4. Same invention.
13	Yes	21	7	· As for claim 12 · Mammalian cells are encompassed within the scope of eucaryotic cell (claim 21), and exemplified in 600650. Thus selection criteria not met.
14	Yes	21	8	· As for claim 13 · CHO cells are encompassed within mammalian cells. While some advantage is indicated [glycosylation], they are exemplified in 600650. Thus selection criteria not met.
15	Yes	22	38	· The amino-acid sequence 1-166 is the sequence for natural erythropoietin, and is common to all specifications. Same invention.
16	Yes	22	39	· As for claim 15. · The leader sequence is explicitly defined in claim 39 of 657555. · The presence of a leader is encompassed within claims to a cDNA molecule. The leader sequence is clearly identified/exemplified in 600650. Thus selection criteria not met.
17	Yes	20 (via 17)	11, 40	· As for claims 15 and 16. · Heterologous promoters explicit in claims 11 & 40. · claims 11 & 40 encompass cDNA encoding erythropoietin. cDNA not a different invention, given gDNA · claim 20 of 600650 does not explicitly claim heterologous promoters. However the claim encompasses such, and their use is common knowledge in the art. Further, there is no surprising result to provide the basis of selection.
18	Yes	21	12, 41	· As for claim 17 · Mammalian cells are encompassed within the scope of eucaryotic cell (claim 21), and exemplified in 600650. Thus selection criteria not met.
19	Yes	21	13, 42	· As for claim 18. · Re 3T3, C127, and CHO cells: see comments under claim 11.
20	Yes	21	12, 41	· Use of a viral vector is indicated in 600650, but not specifically the bovine papilloma virus. However no advantages whatsoever indicated for the use of this particular virus. Thus selection criteria not met. · Claim 20 of 621535 encompasses vectors containing the heterologous promoters of claims 12 and 41.
21	Yes	21	12, 41	· As for claim 20. · Re 3T3, C127, and CHO cells: see comments under claim 11
22	Yes	17	6, 9, 14, 37	· The differences in the sequences of the various specifications is not significant. They relate to the same invention. · Genomic DNA implicit in the claims of the citations.
23	Yes	21	12, 41	· As for claim 21. · neither 600650 nor 657555 refer to mouse metallothionein promoter, but such is encompassed within their claims. The promoter was common knowledge in the art. There is no evidence that a surprising result derives from the use of this promoter. Thus selection criteria not met.
24	Yes	21	12, 41	· As for claim 23. · the particular plasmid construct is encompassed within the claims, and does not appear to provide a selective advantage.
25	Yes	1, 38	15	· Claims 1 & 38 of 600650 encompasses erythropoietin with O-linked glycosylation. · O-linked glycosylation is an inherent result of expression from CHO cells. Expression from CHO cells is exemplified in 600650. Consequently, the selection criteria are not met.
26	Yes	1, 47	16	· As for claims 2 and 3. · growing mammalian cells in fetal serum is common general knowledge, and used in the citations. No surprising advantages identified. Selection criteria not met.
27	Yes	1, 47	17	· As for claim 26. · Re mammalian cells, see comments under claim 10.
28	Yes	1, 47	18	· As for claim 27. · Re COS, 3T3, C127, and CHO cells: see comments under claim 11.
29	Yes	52	20, 48	· Claim 52 of 600650 necessarily embodies the claimed method.
30	Yes	1, 38	21	· See comment for claim 25.
31	Yes	1, 38	22	· See comment for claim 25.
32	Yes	1, 38	23	· See comment for claim 25.
33	Yes	1, 38	24	· See comment for claim 25.

Appendix 5

The AD 1515 Act of 6 Hen. VIII, Ch 15.
(See Merck & Co (Macek’s) Patent, [1967] RPC 157 at 160.)

C A P. XV

An act adnulling second letters patents during the King’s pleasure, making no mention of the first letters patents.

1 Leon. 321.

3 Leon. 242, 247

Second Letters Patents making no mention of the first, adnulled. What shall be expressed in the King’s patents of lands, offices &c before granted to some other.

The Kings Highness of his goodness calling to his remembrance, that where his Grace hath granted to divers of his servants (for their service to his Grace done) lands, tenements, fees, offices, and other things, to have to them during his pleasure; (2) and after other persons, by their sundry suits, have obtained of his Highness other letters patents of the same, not advertising his Grace of his former grants, whereby the said former patentees have been avoided, and put from the advantage of their said former grants and patents, contrary to the intent and grant of our said sovereign lord: (3) Wherefore be it ordained, established and enacted by our said sovereign lord, the lords spiritual and temporal, and the commons, in this present parliament assembled, and by authority of the same, That if any person or persons from henceforth do make suit to the King’s Highness for any lands, tenements, offices, or any other things so by his Grace granted, or hereafter to be granted to any person or persons during his pleasure the said first patentee then being in life, that he do express in his said bill of petition or patent the tenor of the said former patent, and that the King then hath determined his pleasure against the first patentee; (4) or else the second letters patents of any of the premises to any person hereafter to be granted, to be void and of none effect.

II. This act to commence and take effect from the fourth day of April next coming, and not before.

[1996] APO 56

19 November 1996