University of Georgia Research Foundation, Inc v Biochem Pharma Inc

OFFICIAL NOTICE
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Application : No. 670637 in the name of University of Georgia Research Foundation, Inc. and Emory University

Title: Enantiomerically pure b-D-dioxolane-nucleosides

Action: Opposition to an amendment of the application by BioChem Pharma Inc.

Decision: Issued
Abstract

The amendment is allowable.
The specification asserts that the compound b-D-ACPD is a potent anti-HIV agent. The amendment alters the EC₅₀ value for this compound, but does not alter the nature of the invention.
PATENTS ACT 1990
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Re:Patent Application No. 670637 by University of Georgia Research Foundation, Inc. and Emory University, and an opposition to an amendment of the application by BioChem Pharma Inc.

BACKGROUND

Patent application number 50933/93 was filed as an international application designating Australia (number PCT/US93/08044) on 25 August 1993 by the University of Georgia Research Foundation, Inc. and Emory University (hereafter referred to as the Universities). The application claims priority from US 935515 (which was filed on 25 August 1992). The application was examined by the Commissioner, and advertised accepted under the serial number 670637 on 25 July 1996.
BioChem Pharma Inc. (hereafter referred to as BioChem) filed a notice of opposition on 25 October 1996. A decision upholding the opposition on the grounds of novelty and inventive step was issued on 8 November 2000 (see University of Georgia Research Foundation v BioChem Pharma Inc (2000) 51 IPR 222). That decision is presently the subject of an appeal to the Federal Court.
An amendment to the specification was advertised in the Official Journal on 10 August 2000, and a notice of opposition was filed by BioChem on 10 November 2000. The present decision relates solely to the opposition to the amendment.
The matter was heard in Sydney on 28 February 2002. The Universities were represented by Mr David Catterns QC, instructed by Dr Bill Pickering of Blake Dawson Waldron Patent Services. BioChem was represented by Dr Annabelle Bennett SC and Katrina Howard of counsel, instructed by Dr Ken Finney of Cullen & Co.
THE AMENDMENT
The amendment results in the replacement of four pages of the description. There are no amendments directed to the claims of the specification.
GROUNDS OF OPPOSITION
The statement of grounds and particulars specifies the amendment is not allowable under section 102(1). The particulars make it clear that the issue is solely in relation to the amendment of the EC₅₀ value of the compound b-D-ACPD in Table 1 of the specification. The amendment has the effect of replacing the value of 0.9 with 0.067.
EVIDENCE
The evidence in support of the opposition consists of declarations by Dr Marcuccio and Dr Finney.
The evidence in answer consists of a declaration by Professor Schinazi.
The evidence in reply consists of a further declaration by Dr Finney.
THE SPECIFICATION
The technology of the specification is described more fully in my earlier decision (51 IPR 222 at 226-229). For the purposes of the present opposition, all that needs to be understood is that the application relates to compounds for treatment of humans infected with HIV. The claims are directed to three specific compounds and their use in treatment: b-D-ACPD, b-D-APD and b-D-DAPD (as well as some simple ester derivatives). The description relates to a broader range of compounds, but the key disclosure is that in Table 1 (reproduced in full in Annex 1). The Table gives EC₅₀ values for four compounds: b-D-ACPD (i.e. R = Cl in Table 1), b-L-ACPD (R = Cl), b-D-DAPD (R = NH₂) and b-D-DXG (R = OH). (The amendment in question would alter the EC₅₀ value for b-D-ACPD, and leave the other information unchanged.)
DECISION
The present case requires an analysis in two parts. The first question is whether the amendment is allowable under section 102(1). If the amendment is not allowable, the second question is whether the amendment is otherwise allowable as the correction of a clerical error or obvious mistake (section 102(3)).
The relevant law
This opposition relates to the operation of section 102 of the Act, the relevant parts of which read:
(1) An amendment of a complete specification is not allowable if, as a result of the amendment, the specification would claim matter not in substance disclosed in the specification as filed.
(2) An amendment of a complete specification is not allowable after the relevant time if, as a result of the amendment:
(a)       a claim of the specification would not in substance fall within the scope of the claims of the specification before amendment; or
(b)       the specification would not comply with subsection 40(2) or (3).
(2A) For the purpose of subsection (2),
relevant time means:
(a)       in relation to an amendment proposed to a complete specification relating to a standard patent - after the specification has been accepted; …
(2B) …
(3) This section does not apply to an amendment for the purpose of correcting a clerical error or an obvious mistake made in, or in relation to, a complete specification.
There was agreement that the test of “in substance disclosed” in section 102(1) is similar to the test for fair basis. Dr Bennett submitted that in assessing whether an invention is in substance disclosed, it is also necessary to consider whether any amendment to the description produces a change in the nature of the invention as described. If there is such a change, then the assertion of the claimed matter as an invention is not in substance disclosed (see Enichem Synthesis SpA v Ciba-Geigy AG (1996) AIPC 91-276 and Lumenyte International Corp v Light Transmission Cables Pty Ltd [1998] APO 20). Mr Catterns submitted that this matter was not relevant to section 102, but only went to the question of the priority date to be accorded to any matter claimed (according to section 114). It is necessary to review the law on section 102 in order to resolve this matter.
The operation of section 102 was considered in RGC Mineral Sands Pty Ltd v Wimmera Industrial Minerals Pty Ltd (1998) 89 FCR 458. Carr and Goldberg JJ said:
“That subsection requires one first to identify precisely what is the amendment. In this case that is done by identifying the difference between the specification as accepted (and as it stood at the hearing of the motion at first instance) on the one hand and, on the other hand, as the specification would read if amended in the manner sought. Then one reads the specification as a whole (as so amended in the manner sought) to see whether as a result of the amendments sought (which must mean by reason of the amendment sought) the specification would claim matter not in substance disclosed in the specification as filed. The subsection focuses on the amendment proposed and it must be that amendment which has the result of pushing the claimed matter over the line defined by the expression ‘matter not in substance disclosed in the specification as filed’. The key point to keep in mind is, as counsel for the respondent contended (in our view correctly), that the words ‘as a result of the amendment’ are not to be confused with the expression ‘after the amendment’.”
[page 466]
It is clear that the first stage is to determine what matter results from the amendment, and the second stage is to determine whether that matter was disclosed in the specification as filed. The determination of whether the matter was in substance disclosed was discussed in Re ICI Chemcals & Polymers Ltd and Lubrizol Corporation Inc (2000) 49 IPR 513. The Full Court stated:
“There is much authority for the proposition that there is a close relationship between the test for fair basing and the question of whether matter is in substance disclosed in a specification. It is unnecessary to consider whether it is appropriate to go so far as to say that the two tests are ‘virtually the same’: Ethyl Corp’s Patent [1972] RPC 169 at 195. For the proposition that there is a close relationship there is no need to do more than refer to the decisions of the Full Court of this court in CCOM at FCR 280-2; Leonardis at FCR 137-43; and RGC Mineral Sands at FCR 460-1. It will, we should think, be a rare case indeed where a claim which claims matter in substance disclosed in the specification as filed is not, equally, fairly based on the matter described in the specification (and vice versa)”
[page 548-9]
I conclude that the fair basis approach is generally useful in determining whether a matter is in substance disclosed. Up to this point, I believe that the parties are generally in agreement on the state of the law. The difficulty arises in that the fair basis test can be applied in two different situations: there is the internal fair basis of a claim on the description, and the external fair basis of a claim on the description of a different document. Internal fair basis is the normal way in which the issue arises, and is assessed using the “real and reasonably clear disclosure” test. This is relevant when considering section 102(2)(b). External fair basis is the form of the issue raised by section 102(1). This aspect of fair basis was considered at length in Coopers Animal Health Ltd v Western Stock Distributors Pty Ltd (1987) 76 ALR 429, which concerned the question of the priority date to be accorded to the claims of a petty patent. The claims were entitled to priority from a provisional application if they were fairly based on the provisional specification. The Federal Court decided that the claims of the petty patent were not fairly based on what was disclosed in the provisional specification because the claims were directed to an invention that was different to that in the provisional, rather than a more specific form of the invention. Significantly, the inventions were sufficiently different that different inventive steps were apparent. I believe that the Coopers approach is a part of the law that is relevant to section 102. Consequently it is necessary to compare the nature of the invention as claimed in the later document with the invention as described in the earlier document and not only examine the scope of the claims. (I note that this is the same conclusion reached in the Enichem and Lumenyte decisions.)
However, I am also mindful of what was said by the Full Bench of the Federal Court in Gambro Pty Ltd v Fresenius Medical Care South East Asia Pty Ltd [2000] FCA 1044 at [18]:
“the requirements of s 102 should generally be given a liberal construction because there is a strong public interest that inventive genius be encouraged”
I conclude that the Coopers approach is appropriate to the determination under section 102(1). However, the Coopers comparison should be applied liberally and not in an overly meticulous way.
In substance disclosed
The amendment does not alter the scope of any of the claims in terms of the subject matter that is covered, and no new compounds are disclosed. There is clearly internal fair basis for the claims.
The amendment alters the EC₅₀ value of b-D-ACPD from 0.9 to 0.067. The significance of this change is that a lower EC₅₀ values indicates that the compound is a more effective anti-viral agent. On the page 26, which is the page immediately previous to the Table, the specification states:
“Using this assay, it has been discovered that a small number of b-D-dioxolanyl purine nucleosides are potent anti-HIV agents. Specifically, as indicated in Table 1, compounds 21, 25, and 26 exhibit a low effective median concentration, ranging from 0.027 to 0.69 µM.”
This portion of the text is not altered by the amendment. Compound number 21 is b-D-ACPD. The assertion is that b-D-ACPD is a potent anti-HIV agent. However, its EC₅₀ value (prior to amendment) was outside the range specified. Professor Schinazi noted that the EC₅₀ value is an inherent property of the compound:
“I would also observe that regardless of what value is recorded the statement in the application at page 26, lines 18-20 that these compounds are potent anti-HIV agents is, and has always been, correct. The activity of any compound is an inherent property of that compound. The fact that the activity of a compound is incorrectly recorded obviously does not change the nature of or the activity of that compound.”
[paragraph 13 of the declaration in answer]
I accept that the activity of the compound has not changed. However, the question required under the Act is whether the invention as asserted by the specification has changed. If the disclosure in the specification is properly viewed as teaching that b-D-ACPD was not a potent anti-HIV agent (because its EC₅₀ value was above 0.69), then an amendment to bring the EC₅₀ value into the potent range would change the nature of the invention. Consequently the focus must be on the specification, and what it asserts.
There is an interesting statement in the declaration of Professor Schinazi dated 30 November 1999, which is included as part of the Exhibit to the declaration in support of Dr Finney. Discussing a different pair of EC₅₀ values (given to the compound b-D-ACPD in other published sources) he stated at paragraph 46:
“Dr Evans points out that I presented an EC₅₀ of 0.067 for (-)-b-2-amino-6-chloropurine in RFS-5, whereas the value given in Table III of RFS-3 is 0.09. When rounded, those numbers are merely 20% different, and not even approaching one log. That sometimes occurs in biological systems, and can also be a function of the purity of the drug tested.”
It seems that a difference of as much as 20% is not significant, but that a tenfold difference would be (i.e. one log unit). If this is correct and represents what a skilled reader would have understood, then a value of 0.9 is consistent with the upper limit of 0.69. On the other hand, Dr Marcuccio declared that there is an inconsistency between the values in the description and the Table (paragraph 7). However, Dr Marcuccio accepts that the inconsistency is evidence of an error in the specification, either in the upper value of the range of potent anti-HIV values or in the EC₅₀ of b-D-ACPD. I infer from this that Dr Marcuccio interprets the specification as teaching that b-D-ACPD is a potent anti-HIV agent, in spite of the inconsistency.
There is clearly an assertion that b-D-ACPD is a potent anti-HIV agent. The EC₅₀ value is not literally within the range on page 26 of the specification, but the value is not substantially different. It is most likely that the specification teaches b-D-ACPD is a potent anti-HIV agent.
An amendment to alter the EC₅₀ value of b-D-ACPD to 0.067 changes the exact activity level, but it does not change the fact that it is a potent anti-HIV agent. Consequently there is no change in the nature of the invention as a result of the amendment, and the amendment is allowable under the Coopers approach.
Mr Catterns stated that this case is similar to Merck & Co Inc v Sankyo Co Ltd (1992) 23 IPR 415, 427. In Merck the specification originally identified the substituent at the 25-position of an avermectin as n-propyl, but this was later corrected to iso-propyl. It was accepted that the amendment did not disclose new matter but correctly identified what had already been disclosed. In the present case it is not certain that the amendment corrects an error. b-D-ACPD has a range of EC₅₀ values in the assays reported by Professor Schinazi (Exhibit RFS-10, which appears in an Exhibit attached to the declaration in support of Dr Finney). This indicates that there is not a simple inherent EC50 value for b-D-ACPD (contrary to the assertion of Professor Schinazi). Rather there appears to be a range of EC50 values for b-D-ACPD depending on precisely how the assay is carried out. This leads to the reasonable conclusion that the Universities are making a choice of a preferred value rather than a correction of the inherent value. I do not believe that the analogy with the Merck case assists the Universities.
Clerical error/obvious mistake
Since the amendment does not offend section 102(1), it is immaterial whether the amendment is for the purpose of correcting a clerical error or obvious mistake. However, as this was the subject of submissions, I will deal briefly with the point.
It appears from the evidence that it is possible that there is an error in the specification in relation to the EC₅₀ value of the compound b-D-ACPD. While there was not agreement that the amendment as proposed would correct the error, I will proceed on the basis that it would correct an error (although I make no finding on this point). However, the Act only provides an exception in the case of two types of errors: clerical errors and obvious mistakes. There is no exception in the case of other types of errors.
Obvious mistake: The key features of an obvious mistake are that the mistake must be obvious, and the correction must also be obvious (General Tire and Rubber Co (Frost’s) Patent [1972] RPC 259). While it is clear that there is a literal inconsistency between page 26 and the Table in terms of the EC₅₀ value of b-D-ACPD, it is not certain that a mistake is obvious. However, regardless of this, it cannot be said that the correction was obvious. The “correct” value could only be determined by experimentally determining the EC₅₀ value (see paragraph10 of the declaration in answer of Professor Schinazi). This is not a case of obvious mistake, and the Universities did not assert that there was an obvious mistake.
Clerical error: A clerical error is an error that occurs in the mechanical process of writing or transcription (R v Commissioner of Patents; Ex parte Martin (1953) 89 CLR 381). Professor Schinazi was of the view that a clerical error had occurred:
“I am unaware as to how the wrong EC₅₀ for b-D-ACPD was recorded in Table 1 of the patent application. As shown in Exhibit RFS I the correct values were available. I can only conclude that this error was simply a clerical error in the transcription of these results.”
[paragraph 12 of his declaration in answer]
It appears from Re Dempster Brothers Inc (1974) 44 AOJP 4276 that circumstantial evidence of an error can be acceptable, for instance when it is possible to exclude other sources of error. There is no evidence from anyone directly responsible for preparing the patent specification. The sole basis for inferring that a clerical error had occurred is that the original source data had the “correct” value of 0.067. Professor Shinazi exhibits a document containing the correct EC₅₀ value. His statement in relation to this document is less than clear:
“The data set out in this Exhibit were generated by my research group. These results were used in the generation of Table 1 of the patent application and were obtained prior to the filing of the patent application.”
[paragraph 6 of the declaration in answer]
It seems likely that the Exhibit is a document created after the preparation of the patent application, but containing a summary of information created prior to the preparation of the patent application. Consequently the Exhibit was not used in the preparation of the patent application, and it remains unclear at what point the EC₅₀ value changed from the “correct” figure of 0.067 to the figure of 0.9 that appeared in the specification. I note that no compound in the Exhibit has an EC₅₀ of 0.9, so the error is not simply one of misreading the source information. Additionally, the Exhibit itself contains at least one error: the compound that is allegedly b-D-DAPD is stated to have a 2,4-Di-NH₂P as the base moiety (whereas the compound actually has a 2,6-Di-NH₂P moiety). Counsel agreed that this must be an error. This reinforces the view that the information in the Exhibit was not the only source of information for preparing the specification, since a correction of this incorrect information also occurred.

Dr Bennett asserted that the evidence does not exclude other sources of error. In particular, Dr Bennett suggested that testing b-D-ACPD gives a range of EC₅₀ values, and it was equally likely that 0.9 was one of the EC₅₀ values available. This is supported by the wide range of EC₅₀ values for b-D-ACPD appearing in Exhibit RFS-10 to the Schinazi declaration of 14 January 1999.
The evidence raises as many questions as it answers, and in the absence of a fuller explanation of where the error occurred, it is doubtful whether a clerical error has been established.
CONCLUSION
The amendment does not violate section 102(1), and is thus allowable. It is immaterial that it has not been established that the amendment corrects an obvious mistake or clerical error.
I allow the amendment.
Costs
The applicant has been successful in this action, and it is appropriate that costs follow the event. I award costs in accordance with Schedule 8 against BioChem Pharma Inc.
Dr S.D.Barker
Delegate of the Commissioner of Patents
Patent attorneys for the applicant : Blake Dawson Waldron Patent Services
Patent attorneys for the opponent : Cullen & Co
ANNEX 1: TABLE 1 OF THE SPECIFICATION
Table 1

R Anomer EC₅₀*

Cl b-D 0.9

Cl b-L 13.4

NH₂ b-D 0.7

OH b-D 0.03
* Mean of at least 2 assays, using different donor cells. Standard error estimated at plus or minus 10%
NOTES:
1. "The EC50 is the concentration of compound at which there is a 50% inhibition of viral growth." (page 26 of the specification)
2. An amendment item dated 7 January 2000 proposes amending the EC₅₀ value for the first compound to 0.067.

[2002] APO 17

10 May 2002