Ex Parte Palomba et alDownload PDFBoard of Patent Appeals and InterferencesMay 12, 200910285874 (B.P.A.I. May. 12, 2009) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 10/285,874 10/31/2002 Maria Lia Palomba MSK.P-026-4 4321 52334 7590 05/13/2009 Larson & Anderson, LLC re: MSK P. O. BOX 4928 DILLON, CO 80435-4928 EXAMINER BRISTOL, LYNN ANNE ART UNIT PAPER NUMBER 1643 MAIL DATE DELIVERY MODE 05/13/2009 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte MARIA LIA PALOMBA, ALAN HOUGHTON, JEDD WOLCHOK, DAVID A. SCHEINBERG, and WENDY K. ROBERTS __________ Appeal 2008-4403 Application 10/285,874 Technology Center 1600 __________ Decided:1 May 13, 2009 __________ Before DEMETRA J. MILLS, LORA M. GREEN, and JEFFREY N. FREDMAN, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method for stimulating an immune response, which the Examiner has rejected as failing the enablement requirement and as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. 1 This case was heard in Oral Hearing on April 21, 2009. Appeal 2008-4403 Application 10/285,874 2 Statement of the Case Background “Differentiation antigens are tissue-specific antigens that are shared by autologous and some allogeneic tumors of similar derivation, and on normal tissue counterparts at the same stage of differentiation” (Spec. 1, ll. 22-25). According to the Specification, “[u]nfortunately, in most cases, the immune system of the individual is tolerant of these antigens, and fails to mount an effective immune response” (Spec. 2, ll. 14-15). The Claims Claims 1-3, 10-12, and 23-29 are on appeal2. We will focus on claim 1, which is representative and reads as follows: 1. A method for stimulating an immune response to a tissue expressing CD20 in a subject individual of a first species, comprising administering to the subject individual an immunologically-effective amount of xenogeneic or xenoexpressed CD20 antigen. The Cited Art Haupt et al., The Potential of DNA Vaccination against Tumor- Associated Antigens for Antitumor Therapy, 227 EXP. BIOL. MED. 227-237 (2002). Vincenzo Bronte, Genetic Vaccination for the Active Immunotherapy of Cancer, 1 CURRENT GENE THERAPY 53-100 (2001). You et al., Targeting Dendritic Cells to Enhance DNA Vaccine Potency, 61 CANCER RESEARCH 3704-3711 (2001). Nettelbeck et al., Gene Therapy, 16 TRENDS IN GENETICS 174-181 (2000). Browne et al., Coupling and Uncoupling of Tumor Immunity and Autoimmunity, 190 J. EXPERIMENTAL MEDICINE 1717-1722 (1999). 2 The Examiner withdrew claims 4-9, 13, and 14 based upon a restriction requirement (App. Br. 1). Appeal 2008-4403 Application 10/285,874 3 H. Niemann, Transgenic farm animals get off the ground, 7 TRANSGENIC RESEARCH 73-75 (1998). Mahato et al., Development of Targeted Delivery Systems for Nucleic Acid Drugs, 4 J. of DRUG TARGETING 337-357 (1997). Tedder et al., Cloning of a Complementary DNA Encoding a New Mouse B Lymphocyte Differentiation Antigen, Homologous to the Human B1 (CD20) Antigen, and Localization of the Gene to Chromosome 19, 141 J. IMMUNOLOGY 4388-4394 (1988). The Issues A. The Examiner rejected claims 1-3, 10-12 and 23-29 under 35 U.S.C. § 112, first paragraph as failing to comply with the enablement requirement (Ans. 6-13). B. The Examiner rejected claims 1-3, 10-12 and 23-29 under 35 U.S.C. § 103(a) as obvious over Bowne, You, Tedder, and Mahoto (Ans. 13). A. 35 U.S.C. § 112, first paragraph Enablement Rejection The Examiner finds that: [T]he specification does not reasonably provide enablement for overcoming tolerance to endogenous CD20 in any subject by stimulating any immune response with any xenogeneic CD20 antigen where the CD20 antigen is encoded by DNA alone much less in a liposome encapsulated DNA form or coated on a gold particle DNA form or in any expression vector encoding the DNA where the subject individual of a first species is any subject much less a human and where the immune response is immunoprotective against growth of any CD20-expressing tumor. (Ans. 6). Appellants contend that the “Examiner has offered no reasons why a person in the art would need undue experimentation to extend the teachings Appeal 2008-4403 Application 10/285,874 4 of the specification and the animal model results of vaccination against CD20 to other vaccinations against CD20” (App. Br. 6). In view of these conflicting positions, we frame the enablement issue before us as follows: Have Appellants demonstrated that the Examiner erred in concluding that it would have required undue experimentation to stimulating an immune response to a tissue expressing CD20 by administering a xenogeneic or xenoexpressed CD20 antigen? Findings of Fact (FF) Breadth of the Claims 1. The Examiner finds that the “claims encompass using an immunologically effective amount of any DNA encoding a xenogeneic CD20 antigen or liposomes comprising DNA encoding the xenogeneic CD20 antigen or gold particles coated with DNA encoding the xenogeneic CD20 antigen” (Ans. 8). Presence of Working Examples 2. The Specification teaches that “[m]ice immunized with the human minigene (pNERIS-H8) displayed a slower pace of tumor take, as shown in panel 3a and 3b. Long-term survival, defined as survival up to 60 days post-challenge, was modestly but statistically better in mice immunized with pCR3-H8” (Spec. 7, ll. 1-4). 3. The Specification teaches that “T-cell responses against mouse CD20 were observed following vaccination with human CD20 DNA” (Spec. 7, ll. 8-9). Appeal 2008-4403 Application 10/285,874 5 4. The Specification teaches that “[a]nalysis of the sera from mice immunized with both human and mouse minigenes revealed the presence of anti CD20 antibodies in about 80% of the animals tested” (Spec. 8, ll. 2-4). Amount of Direction or Guidance Presented 5. The Specification teaches that the “[a]dministration of a protein/peptide xenogeneic or xenoexpressed CD20 antigen can be accomplished by several routes. First, the xenogeneic CD20 may be administered as part of a vaccine composition” (Spec. 4, ll. 8-10). 6. The Specification teaches that “[x]enogeneic CD20 antigen may also be introduced in accordance with the invention using a DNA immunization technique” (Spec. 4, ll. 27-28). 7. The Specification teaches methods for routine cloning of the CD20 sequence by reverse transcriptase PCR (see Spec. 9-10, Example 1). 8. The Specification teaches “preferred xenogeneic antigens will be rodent antigens, for example mouse, but could come from other mammals such as dog, cat, cow, or sheep, or from birds, fish, amphibian, reptile, insect or other distantly related species” (Spec. 3, ll. 25-27). State of the Art and Unpredictability of the Art 9. Haupt teaches that “DNA immunization, is known to induce both antigen-specific cellular as well as humoral immune responses” (Haupt 228, col. 1). 10. Haupt teaches that “[r]ecently published studies have shown that xenogeneic DNA immunization exploiting small differences in expressed tumor antigen sequence can result in immune recognition of self- Appeal 2008-4403 Application 10/285,874 6 molecules in mice, whereas immunization with syngeneic DNA failed to do so” (Haupt 231, col. 1-2). 11. Haupt teaches that “[a]nimals immunized with xenogeneic human gp100 DNA were significantly protected from tumors after a challenge with a syngeneic melanoma expressing gp100” (Haupt 231, col. 2). 12. Bronte teaches that “[i]mmunization with xenogeneic TAA was shown to break tolerance, but their serendipitous isolation makes it difficult to apply this strategy to the therapy of human tumors. What species will supply the xenogeneic antigen? Should we use porcine, mouse, sheep or monkey homologous antigen? It is clear that we cannot proceed empirically in this search” (Bronte 84, col. 1-2). 13. Nettelbeck teaches that “[m]any laboratories have therefore focused on the design of improved promoters for cancer gene therapy and this review will give a brief account of the recently successful developments in this research area” (Nettelbeck 175, col. 1). Principles of Law “In order to satisfy the enablement requirement of section 112, an applicant must describe the manner of making and using the invention ‘in such full, clear, concise, and exact terms as to enable any person skilled in the art ... to make and use the same ....’ 35 U.S.C. § 112, para. 1.” Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1322 (Fed. Cir. 2005). Factors to be considered in determining whether a disclosure would require undue experimentation . . . include (1) the quantity of experimentation necessary, (2) the Appeal 2008-4403 Application 10/285,874 7 amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). The Examiner has the initial burden to establish a reasonable basis to question the enablement provided for the claimed invention. See In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993) (Examiner must provide a reasonable explanation as to why the scope of protection provided by a claim is not adequately enabled by the disclosure). Analysis The Specification provides substantial teachings regarding methods for stimulating an immune response using a xenogeneic CD20 antigen, including working examples of such a response in mouse model systems (FF 2-6). The Specification also teaches how to obtain CD20 antigens from desired species by RT-PCR (FF 7). The prior art cited by the Examiner, Haupt and Bronte, both teach that DNA immunization stimulates an immune response and that the immune response may protect against tumors (FF 8-12). Bronte does recognize some unpredictability in selection of the xenogeneic antigen (FF 12). Nettelbeck shows that promoters necessary for cancer gene therapy are taught by the prior art (see FF 13). Balancing the Wands factors, we agree with Appellants that undue experimentation would not have been required to make and use the claimed invention. To the extent that the Examiner argues the “how to make” prong, Appeal 2008-4403 Application 10/285,874 8 the Specification and prior art clearly teach how to obtain CD20 from any desired xenogeneic species and also teach how to make plasmids with CD20 and promoters which will function to express that CD20 in the desired cell types (FF 7, 8, 13). The Specification also teaches how to immunize using the xenogeneic antigens after the CD20 containing plasmids are synthesized (FF 2-6). With regard to the “how to use” prong, the Specification and prior art demonstrate that xenogeneic antigens clearly satisfy the claim requirement to “stimulate an immune response” (see FF 2-5, 8-12). There is no doubt that xenogeneic CD20 stimulated an immune response in mice (FF 2-5). There is no reasonable reason to doubt that administration of xenogeneic CD20 would stimulate an immune response in humans or any other desired species, given the disclosures of the Specification and prior art (FF 2-5, 8- 12). The entire discussion by the Examiner regarding “vaccination” is not relevant to the instant claims, which do not use the word “vaccination”, and do not even require prevention of a disease or disorder (see Ans. 18). See In re Hiniker Co., 150 F.3d 1362, 1369 (Fed. Cir. 1998) (“the name of the game is the claim”). The issue in claim 1 is whether administration of a xenogeneic CD20 antigen will stimulate an immune response (see Claim 1). The Examiner has not provided any evidence or reasoning to suggest that this will not occur, and in fact, acknowledges that Appellants have elicited such a response (see Ans. 20). It may be that the Examiner intends this to be a scope of enablement rejection, as nonenabling for humans, or in producing a prophylactic or Appeal 2008-4403 Application 10/285,874 9 therapeutic effect. If so, we are not persuaded by the scope of enablement argument either, since there is specific evidence in the Specification that the method has some therapeutic effect in a mouse model system and the Examiner has provided no specific evidence that the method would not function in humans or other species or using other plasmid constructs (FF 2- 13). Moreover, the Examiner's apparent position that the Specification cannot teach how to use the claimed method unless it teaches solutions to all possible species and all possible plasmid vectors is contrary to controlling case law. See, e.g., In re Brana, 51 F.3d 1560, 1568 (Fed. Cir. 1995). In Brana, the claims were directed to compounds disclosed as anti- cancer agents. Id. at 1562. The USPTO rejected the claims as nonenabled, id. at 1563-64, despite working examples in Brana's specification showing treatment of cancer in a mouse model. Id. at 1562-63. The USPTO argued that the results of the mouse testing “are not reasonably predictive of the success of the claimed compounds for treating cancer in humans.” Id. at 1567. The court concluded that this position “confuses the requirements under the law for obtaining a patent with the requirements for obtaining government approval to market a particular drug for human consumption.” Id. The Brana court held that “[u]sefulness in patent law, and in particular in the context of pharmaceutical inventions, necessarily includes the expectation of further research and development. The stage at which an invention in this field becomes useful is well before it is ready to be administered to humans.” Id. at 1568. Appeal 2008-4403 Application 10/285,874 10 The facts in the instant case are better for Appellant than the facts in Brana, since not only does the Specification show working examples, but the cited art also shows evidence of success (FF 2-12). Conclusions of Law We conclude that Appellants have demonstrated that the Examiner erred in finding that it would have required undue experimentation to stimulating an immune response to a tissue expressing CD20 by administering a xenogeneic or xenoexpressed CD20 antigen. B. 35 U.S.C. § 103(a) over Bowne, You, Tedder, and Mahoto The Examiner finds that: It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to substitute the human TRP/PCR3 vector in the method taught by Bowne with an expression vector construct containing a CD20 gene (i.e., a human CD 20 for injection into mice or the mouse CD20 gene for injection into a xenogenic recipient) of Tedder to yield a operable naked vector of You, and to further encapsulate the expression vector with liposomes of Mahato or to coat gold particles as taught by Bowne, in order to provide an enhanced stimulation of an active and specific immune response to a xenogeneic CD 20 antigen. (Ans. 14-15). Appellants contend that the “issue presented in this appeal is whether the application is entitled to the benefit of the December 10, 1997 filing date of PCT Application No. PCT/US97/22669. If the application is so entitled, then the references cited are not prior art and the rejection must be reversed” (App. Br. 9). Appeal 2008-4403 Application 10/285,874 11 In view of these conflicting positions, we frame the obviousness issue before us as follows: Have Appellants demonstrated that the Examiner erred in finding that the disclosure in WO 98/25574 (PCT/US97/22669) does not reasonably convey to one of ordinary skill in the art that Appellants possessed the instantly claimed subject matter? Findings of Fact 14. WO 98/25574 teaches that “[d]ifferentiation antigens are tissue- specific antigens that are shared by autologous and some allogeneic tumors of similar derivation” (WO 98/25574 1, ll. 4-5). WO 98/25574 teaches that “differentiation antigens expressed by melanoma cells include Melan- A/MART-1, Pmel17, tyrosinase, and gp75” (WO 98/25574 1, ll. 9-10). 15. WO 98/25574 teaches that “[d]ifferentiation antigens expressed by lymphomas and leukemia include CD19 and CD20/CD20 B lymphocyte differentiation markers” (WO 98/25574 1, ll. 10-12). 16. WO 98/25574 teaches that “[f]or treatment of cancers where the tumor expresses differentiation antigens therefore, it would be desirable to have a method for stimulating an immune response against the differentiation antigen in vivo” (WO 98/25574 1, ll. 22-24). 17. WO 98/25574 teaches that “the therapeutic differentiation antigen may be a differentiation antigen (wild-type or mutant) of the same type from a species different from the individual being treated. For example, a mouse differentiation antigen can be used to simulate an immune response to the corresponding differentiation antigen in a human subject” (WO 98/25574 2, ll. 13-16). Appeal 2008-4403 Application 10/285,874 12 18. WO 98/25574 teaches that “an immune response against a target differentiation antigen can be stimulated by the administration of xenogeneic differentiation antigen of the same type” (WO 98/25574 7, ll. 2- 4). 19. WO 98/25574 teaches that “administration of human gp75 broke the tolerance to gp75 in C57BL/6 mice” (WO 98/25574 11, ll. 4-5). 20. WO 98/25574 teaches that “[m]ice immunized with human gp75+ SK-MEL-19 were also markedly protected against B16F10 melanoma compared to unimmunized mice” (WO 98/25574 11, ll. 30-31). 21. Tedder teaches “the primary structure of the mouse homolog of the human B1 [CD20] molecule deduced from a cloned cDNA” (Tedder 4388, col. 2). Principles of Law “In order to gain the benefit of the filing date of an earlier application under 35 U.S.C. § 120, each application in the chain leading back to the earlier application must comply with the written description requirement.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (citing In re Hogan, 559 F.2d 595, 609 (CCPA 1977)). In order to satisfy the written description requirement, “the applicant must … convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention.” Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991). Thus, “[t]he possession test requires assessment from the viewpoint of one of skill in the art.” Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1320 (Fed. Cir. 2003). Appeal 2008-4403 Application 10/285,874 13 Analysis WO 98/25574 broadly discusses the use of any differentiation antigen, and only lists six different differentiation antigens, including CD20 (FF 14- 15). WO 98/25574 directly teaches stimulation of immune response against differentiation antigens (FF 16). WO 98/25574 also directly teaches a preference for the use of xenogeneic antigens to stimulate the immune response (FF 17-18). Finally, WO 98/25574 teaches that gp75, another of the six differentiation antigens listed, functions to stimulate immune response, break tolerance and provide a protective immune response (FF 19- 20). We agree with Appellants that the disclosure of WO 98/25574, from which the instant application depends, reasonably conveys to the skilled artisan that Appellants were in possession, and enabled for, a method of stimulation of immune responses with xenogeneic differentiation antigens, including CD20 (FF 14-20). We are not persuaded by the Examiner’s argument that WO 98/25574 does not teach “antigenic epitopes of human or murine CD20, embodiments for CD20 proteins/peptide and DNA vectors encoding the CD20 proteins/peptides” (Ans. 24). Claims 1-3, 10-12 and 23-29 do not include any requirement for “antigenic epitopes” and the ordinary artisan using CD20 to stimulate an immune response would have followed the guidance of WO 98/25574 to utilize the whole protein, not particular regions (FF 14- 20). Further, Tedder discloses that the mouse CD20 gene was cloned using standard techniques, and the Examiner has provided no reason to expect Appeal 2008-4403 Application 10/285,874 14 unpredictability in cloning CD20 genes from other species or in moving these cloned genes into DNA vectors as disclosed in WO 98/25574 (FF 21). Since we find that Appellants are entitled to the filing date of WO 98/25574 of December 10, 1997, we find that Bowne and You are not prior art to claims 1-3, 10-12, and 23-29 and the obviousness rejection necessarily is reversed. Conclusion of Law We find that Appellants have demonstrated that the Examiner erred in finding that the disclosure in WO 98/25574 (PCT/US97/22669) does not reasonably convey to one of ordinary skill in the art that Appellants possessed the instantly claimed subject matter. SUMMARY In summary, we reverse the rejection of claims 1-3, 10-12, and 23-29 under 35 U.S.C. § 112, first paragraph enablement. We reverse the rejection of claims 1-3, 10-12, and 23-29 under 35 U.S.C. § 103(a) over Bowne, You, Tedder, and Mahoto. REVERSED lp LARSON & ANDERSON, LLC RE: MSK P. O. BOX 4928 DILLON CO 80435-4928 Copy with citationCopy as parenthetical citation