The Government of the United States of America, as Represented by the Secretary, Department of Health and Human Services & University of Rochester v the University of Queensland and CSL Limited

[2005] APO 50

ABSTRACTS OF DECISIONS

DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS

Application  :          Number 683220 in the name of The Government of the United States of America, as Represented by the Secretary, Department of Health and Human Services and Number 688759 in the name of University of Rochester

Titles:          Self-Assembling Recombinant Papillomavius Capsid Proteins (683220) and Production of Human Papillomavirus Capsid Protein and Virus-Like Particles (688759)

Actions:          Opposition to both applications under section 59 by The University of Queensland and CSL Limited

Decision:          Issued 8 November 2005 .

Abstract

A previous decision (see University of Rochester v The University of Queensland and CSL Limited 2005 APO 34] concluded that the Rochester and NIH applications describe and claim the same invention and that the NIH claims have the earliest priority date to human papillomaviruses VLPs (apart from HPV16).  However, in that decision, Rochester challenged the priority date of the NIH application with regard to the HPV16 strain.  This matter could not be finalised in the earlier decision because of its effect on a co-pending opposition against the NIH application (see Secretary, Department of Health and Human Services v The University of Queensland and CSL Limited (2005) APO 33). All parties in both oppositions were therefore given an opportunity to provide submissions on the issue of priority for both the NIH and Rochester applications and the consequential effect this would have in relation to novelty. This second (current) decision finalises the issues left unresolved in both of the earlier oppositions.

The current decision found that the Rochester application was entitled to the earlier priority with respect to the HPV16 strain and deprived the NIH claims of their novelty as they broadly relate to the strain HPV16. 

PATENTS ACT 1990

DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS

Re:Patent Applications No. 683220 by The Government of the United States of America, as Represented by the Secretary, Department of Health and Human Services and 688759 University of Rochester oppositions thereto under section 59 by The University of Queensland and CSL Limited.

BACKGROUND

1. Patent application 683220 (hereafter the "NIH application") was filed under the provisions of the PCT on 3 September 1993 in the name of The Government of the United States of America, as Represented by the Secretary, Department of Health and Human Services claiming priority from two US basic applications (941371 and 32869) filed on 3 September 1992 and 16 March 1993 respectively.  Patent application 688759 (hereafter the “Rochester application”) was filed under the provisions of the PCT on 8 March 1994 in the name of University of Rochester claiming priority from two US basic applications (28517 and 207309) filed on 9 March 1993 and 7 March 1994 respectively.

1. Neither the Rochester nor the NIH applications were published before the filing date of the other.  However, both are Australian patent applications and if one had an earlier priority date than the other application, it potentially could form part of the "whole of contents" novelty prior art base for that other application [Patents Act 1990 section 7(1)(c)].  In this regard, it is important to note that they have overlapping possible priority dates, which I have summarised in the table below:

Number	Inventive Group	earliest priority date	dates of other priority documents	filing date
683220	NIH	3 Sept 1992	16 Mar 1993	3 Sept 1993
688759	Rochester	9 Mar 1993	7 Mar 1994	8 Mar 1994

1. Both applications were opposed by The University of Queensland and CSL Limited (hereafter Queensland University).  I issued separate substantive decisions on both oppositions on 13 July 2005 [Secretary, Department of Health and Human Services v The University of Queensland and CSL Limited (2005) APO 33 and University of Rochester v The University of Queensland and CSL Limited (2005 APO 34) hereafter the “earlier decisions”].

1. Despite the similarity of the subject matter of NIH and Rochester, the opponent did not rely on either application in the co-pending opposition.  It became apparent however in the substantive hearing on Rochester that the NIH application (with its earliest priority date) was a critical citation in respect of the Rochester claims and therefore I invoked regulation 5.11 at the substantive hearing to introduce the NIH application into the Rochester opposition.

2. Rochester was provided with an opportunity to address the NIH application after the hearing. In their submissions, they did not attempt to distinguish their claims from the disclosure in the NIH application but rather argued that the NIH application was not entitled to its earliest priority date with respect to a particular commercially important strain of papillomavirus (HPV16).  After considering the two patent applications in light of Rochester’s submissions, I found (in the Rochester decision) that the NIH application with its earliest priority date deprived Rochester's claims 1-11, 13-21, 23 - 32 of their novelty as they broadly relate to human papillomaviruses VLPs (other than HPV16).

1. However, the issue of the novelty of HPV16 remained unresolved.  If Rochester's arguments were correct, then NIH potentially has a later priority date for HPV16 constructs than Rochester which means that Rochester could deprive the NIH claims of their novelty with regard to HPV16.  This issue could not be dealt with in either of the earlier decisions because the Rochester application had not been formally admitted into the NIH opposition proceedings as part of the evidence or under regulation 5.11.  Further, NIH had not been given an opportunity to defend their priority date, challenge the earliest priority date of Rochester application or otherwise distinguish their claims from the Rochester disclosure. 

1. As a consequence, the earlier substantive decisions noted that the novelty issues in both the Rochester and NIH oppositions could not be finalised until their respective priority dates can be determined with respect to HPV16.  The substantive decisions therefore deferred consideration of the Rochester/NIH novelty issue in relation to HPV16.  All parties in both oppositions were invited to provide evidence or make representations on the following questions:

   ·    What is the first valid priority claim to immunologically correct HPV16 VLPs in both NIH (683220) and Rochester (688759)?; and

   ·    If Rochester was found to have a later priority date than NIH, would NIH [(or a related non-patent citation from the same research group (Kirnbauer 3)] deprive the Rochester claims of novelty with respect to HPV16? or

   ·    If NIH was found to lose its priority date, would Rochester deprive the NIH claims of novelty with respect to HPV16?

2. None of the parties provided any submissions of any substance.  Given this I will proceed to finalise my decision with respect to the above questions for both oppositions based on the material already before me. 

   SPECIFICATIONS

   Descriptions of both NIH and Rochester

1. Both the NIH and Rochester specifications relate to papillomaviruses, one of which (the HPV16 strain) has been associated with a high risk for cervical cancer in women.  A vaccine which induces neutralising antibodies to particular papillomavirus genotypes could potentially prevent infection by the virus and possibly lower the rate of cervical cancer.

1. Both specifications describe the expression of the L1 major capsid protein of papillomavirus in a baculovirus/insect expression system.  The resultant product is able to self-assemble into empty capsomer structures called virus-like particles (or VLPs) that closely resemble the intact virion.  Such VLPs are able to generate high levels of neutralising antibodies to the native virus which could potentially be used for HPV vaccine development and for the development of serological tests for the detection of HPV infection. 

1. Importantly, both specifications were able to generate VLPs for the commercially important strain of HPV16 in contrast to previous workers (including the opponent).  Rochester did not speculate why they succeeded where the opponent had previously failed.  However, both Rochester and NIH application used a wild type clone of HPV16 rather than relying on the prototype (Gissman) clone which had been isolated from a particular cervical carcinoma (Seedorf et al 1985) and which was available from GenBank [Accession number K02718] (see page 8, lines 24 et seq).  NIH noted that the prototype clone was unable to self-assemble because of a single point mutation gene at amino acid position 202 (His to Asp).  NIH speculated that previous workers had failed because they used the prototype clone.

1. The opponent argued some time after the substantive hearing that this may not have been the particular reason for their failure.  However, it is now well-accepted (and the parties all acknowledged) that the source of the HPV16 was critical to success in producing HPV16 VLPs.

Claims of NIH (683220)

1. The NIH specification ends with 28 claims.  Apart from the omnibus claims, the only independent claim is claim 1 which defines:

   1.   A genetic construct comprising a papillomavirus L1 conformational coding sequence encoding a papillomavirus L1 capsid protein and a recombinant vector, wherein said construct is capable of directing expression in a host cell of a capsomer structure having conformational epitopes, which are capable of inducing high titre neutralizing antibodies against native papillomaviruses, by self- assembly of said capsomer structure comprising said papillomavirus L1 capsid protein, with the proviso that said recombinant vector is a non-mammalian cell vector and said cell is a non-mammalian host cell".

2. The specific claims which refer to HPV16 are claims 9-11 which read as follows:

9.The construct of claim 8, wherein said human papillomavirus L1 gene is a wild-type HPV16 L1 gene.

10.The construct of claim 1, wherein said sequence encodes the amino acid sequence of SEQ ID NO:2

11.The construct of claim 1, wherein said sequence encodes the nucleotide sequence of SEQ ID NO:2.

1. Claim 9 is dependent on claim 8 and for completeness, I have also outlined this below:

   8.The construct of claim 8, wherein said sequence is derived from a human papillomavirus L1 gene, a bovine papillomavirus.

   Claims of Rochester (688759)

2. The Rochester specification ends with 32 claims, including a number of independent claims which read as follows:

   1. An isolated non-infectious human papillomavirus virus-like particle or capsomere comprising a human papillomavirus L1 capsid protein which is conformationally correct and is recognized by antibodies present in sera obtained from human patients infected with human papillomavirus.

   8. A method of producing an isolated non-infectious human papillomavirus virus-like particle or capsomere in a cell comprising:

   transfecting a cell with a recombinant expression vector containing a human papillomavirus capsid protein coding sequence under conditions facilitating expression of said capsid protein, thereby producing a non-infectious papillomavirus virus-like particle or capsomere comprising an L1 capsid protein for the human papillomavirus, which is conformationally correct and is recognized by antibodies present in sera obtained from patients infected with the human papillomavirus.

   19. A method of producing an isolated non-infectious human papillomavirus virus-like particle or capsomere in an insect cell comprising:

   cloning a human papillomavirus capsid protein coding sequence into a baculovirus transfer vector;

   co-transfecting insect cells with said baculovirus vector and Autographa california nuclear polyhedrosis virus genomic DNA;

   recovering recombinant baculoviruses; and

   infecting said insect cells with said recombinant baculoviruses under conditions facilitating expression of the capsid protein, thereby producing a non-infectious papillomavirus virus-like particle or capsomere comprising an L1 capsid protein for the human papillomavirus, which is conformationally correct and is recognised by antibodies present in sera obtained by patients infected with the human papilloma virus.

   29. An isolated non-infectious recombinant human papillomavirus virus-like particle or capsomere produced according to the method comprising:

   infecting a cell with a recombinant expression vector containing a human papillomavirus type-6 L1 protein coding sequence or a human papillomavius type-11 L1 capsid protein coding sequence under conditions facilitating expression of said L1 capsid protein, thereby producing a non-infectious human papillomavirus virus-like particle or capsomere comprising a human papillomavirus type-6 L1 capsid protein sequence or a human papillomavirus type-11 L1 capsid protein sequence, which is conformationally correct and is recognised by antibodies present in sera obtained from human papillomavirus type-6 infected patients or human papillomavirus type-11 infected human patients, respective (sic), and isolating said particle.

   30.A purified, non-infectious human papillomavirus virus-like particle or capsomere produced from the expression of the human papillomavirus capsid protein coding sequence, said capsid protein consisting of the L1 capsid protein, wherein said particle or capsomere is recognised by antibodies present in sera obtained from human patients infected with the human papillomavirus.

DECISION

Priority date of HPV16

1. The earlier decisions invited the parties involved on both oppositions to provide evidence or make representations on the question of what is the first valid priority claim to immunologically correct HPV16 VLPs in respect of both NIH (683220) and Rochester (688759).  Both NIH and Rochester reported success in generating HPV16 VLPs in their earliest priority documents but neither document recognised the source of HPV16 as being the critical reason for their success.  In fact, the only priority document associated with either application to specifically mention this as a key factor is the NIH complete application itself.  While there is a potential argument that this explicit teaching is necessary for a priority claim to HPV16, no party argued this point.  Instead, Rochester argued that any document which contained a clear teaching to use the wild type strain of HPV16 (as opposed to the Gissman clone) was entitled to claim priority to that strain.  Given that no party presented a contrary view, I agree that such a teaching would enable the production of a HPV16 VLP even though the skilled worker may not have understood the reasons for their success.  In my view, this is sufficient to establish a priority claim.  I will therefore proceed on the basis that the first document to contain a clear teaching to use the wild type strain could claim priority to HPV16.

1. NIH’s earliest priority document (US 941371 filed on 3 September 1992) did not explicitly disclose the source material of HPV16 used to generate VLPs [or the other exemplified strain (BPV1)].  The only guidance in the basic application to choose a particular strain of HPV16 occurs in example 1 (page 18) which refers to full length L1 open reading frames being amplified by the PCR using the cloned prototype of HPV16 as a template and specifically mentions the citation Seedorf et al 1985 which describes the Gissman clone.  According to Rochester, this disclosure would have led the skilled worker to use the prototype HPV16 rather than the wild type strain to isolate L1.  This is a reasonable argument in the absence of any other guidance in the basic application or any contradictory submissions from NIH or the opponent.  I therefore accept that the NIH teaches the skilled worker to use the prototype clone which would not have enabled them to produce an immunologically correct VLP from HPV12.  As a consequence, NIH is not entitled to its earliest priority date but only in respect of HPV16. 

2. Rochester’s earliest priority document (US application 28517 filed on 9 March 1993) also failed to specifically mention the source of the HPV16.  However, there was a detailed protocol for HPV11 which used genomic DNA from virus particles present in a tissue source (the specification at page 12, line 18).  Rochester suggested that this would direct the skilled worker to use the same (or similar) protocol for HPV16 (especially given that clinical samples were readily available).  This means (according to Rochester) that there was a clear teaching to use wild type strain of HPV16 rather than a prototype strain. 

1. I had raised concerns at the substantive hearing about whether there was other teaching in the priority documents which would have led the skilled worker to use the prototype strain.  In particular, I was concerned that Rochester’s first priority document refers to the Gissman clone when describing the HPV16 source (see page 9, lines 10-14).  Prima facie, this appeared to infer that the skilled worker should use the Gissman clone as the source of HPV16.  However, Rochester argued that the passage on page 9 of the first priority document could equally be interpreted as explaining to the skilled worker that the invention could apply to a broad range of HPV types (including [erroneously] the Gissman clone).

2. NIH didn’t provide any contrary submissions and given this, I accept that Rochester’s interpretation is correct.  As a consequence, my view is that the skilled worker was not directed to use the Gissman clone in the Rochester basic document and would simply have followed the detailed protocol outlined in the HPV11 example.  This means that there was a clear teaching to use a wild-type strain which would enable the production of HPV16.  As a consequence, based on the material before me, Rochester is entitled to its earliest priority date with respect to HPV16.  As this is 7 days earlier that the earliest other possible NIH priority claim, Rochester has an earlier priority date than NIH with respect to HPV16.

Novelty

683220

1. Because Rochester has the earlier priority date in respect of HPV16, that application now becomes relevant to the novelty of the NIH claims.  As foreshadowed in the earlier decisions, I therefore invoke regulation 5.11 to introduce the Rochester application in relation to the NIH.  The parties have already had an opportunity to address the Rochester application as required under regulation 5.11(2)(c) by being invited to respond to the question whether Rochester would deprive the NIH claims of novelty with respect to HPV16 (see the third dot point in paragraph 8 above).

1. I did not receive any submissions from any of the parties in relation to this question.  The parties appear to have accepted that the HPV16 VLPs disclosed in both the NIH and Rochester applications were the same.  I agree with this conclusion.  Both applications disclose the expression of a wild type HPV16 L1 gene construct in a baculovirus/insect host expression system and its subsequent self-assembly into a VLP which is both morphologically and immunologically correct. 

1. Claim 1 of the NIH application defines a genetic construct comprising a papillomavirus L1 conformational coding sequence in a recombinant vector which can be expressed in a host cell to form a capsomer structure which can induce high titre neutralizing antibodies with the proviso that the recombinant vector is a non-mammalian cell vector and the host cell is non-mammalian host cell.  All these features are disclosed in the Rochester application as well the capsomer structure itself, a method of generating the capsomer structure, and the use of the capsomer as both a vaccine and diagnostic test.  Rochester also discloses the use of the L2 capsid protein as an optional part of the papillomavirus coding sequence, an insect cell, a baculovirus vector, the wild type HPV16 L1 gene.  This disclosure deprives the NIH claims which encompass the HPV16 strain (ie claims 1-25, 27, 28) of their novelty as they specifically relate to HPV16.  As noted in the previous decision, the same claims as they relate to papillomavirus strains other than HPV16 are entitled to their earliest priority date and are novel in light of the Rochester disclosure.

688759

1. In one of the earlier decisions (University of Rochester v The University of Queensland and CSL Limited 2005 APO 34), I concluded that the NIH application deprived the Rochester claims 1-11, 13-21, 23-32 of their novelty as they broadly relate to human papillomaviruses VLPs.  These findings still apply.  However in the current decision, I have found that Rochester has the earliest priority date in respect of the HPV16 strain alone.  As a consequence, the NIH application is no longer part of the prior art base for novelty for that strain and those parts of the Rochester claims as they specifically relate to the HPV16 strain (ie: parts of claims 1-5, 8-11, 13-16, 19-21, 23-26, 30-32) are therefore novel in light of the NIH application.

   CONCLUSION

2. My view is that the Rochester and NIH applications describe and claim the same invention.  The two applications have overlapping priority dates and neither application was published before the filing date of the other.  As a consequence, both potentially are part of the "whole of contents" novelty prior art base for the other [Patents Act 1990 section 7(1)(c)].  I concluded in a previous decision (see University of Rochester v The University of Queensland and CSL Limited 2005 APO 34] that the NIH claims have the earliest priority date to human papillomaviruses VLPs (except for HPV16).  As a consequence, the NIH application deprived the Rochester claims 1-11, 13-21, 23-32 of their novelty as they broadly relate to human papillomaviruses VLPs (other than HPV16).

1. In the current decision, I have found that Rochester has the earliest priority date in respect of a particular strain of papillomavirus (HPV16).  As a consequence, Rochester deprives those parts of the NIH claims as they specifically relate to HPV16 (ie parts of claims 1-25, 27, 28) of their novelty.  In contrast, the Rochester claims 1-5, 8-11, 13-16, 19-21, 23-26, 30-32 as limited to HPV16 are novel in light of NIH.

1. I consider both applications to contain patentable subject matter and I allow each applicant 60 days from the date of this decision to file suitable amendments to overcome the deficiencies noted in this decision and the respective earlier substantive decisions.

COSTS

1. I had deferred consideration of costs in the previous substantive decisions because there was an outstanding issue of novelty to be resolved.  Having now completed my substantive considerations, I note that the opponent has been partially successful in both oppositions.  However, their conduct of each opposition has been less than ideal.  Resiling from a key position late in the opposition proceedings caused delays and confusion and meant that much of the evidence was irrelevant.  In addition, although the opponent was aware of both applications (having opposed them), they did not cite them in either opposition.  This meant that the Commissioner had to invoke regulation 5.11 at a late stage in proceedings to introduce them into both proceedings causing further unnecessary delays and complications.  In the circumstances, I

   make no award of costs in either proceedings.

   Karen Ayers
   Delegate of the Commissioner of Patents

   Patent attorneys for NIH  :                   F.B. Rice & Co., Sydney
   Patent attorneys for Rochester:  Phillips Ormonde & Fitzpatrick, Melbourne
   Patent attorneys for the opponent  :      Fisher Adams Kelly, Brisbane