Ex Parte Hansen et al

Patent Trial and Appeal Board

Dec 14, 2017

13114122 (P.T.A.B. Dec. 14, 2017)

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. 13/114,122 05/24/2011 Hans J. Hansen IMMU-0018US8 1900 37013 7590 12/18/2017 Rossi, Kimms & McDowell LLP 20609 Gordon Park Square Suite 150 Ashburn, VA 20147 EXAMINER SCHWADRON, RONALD B ART UNIT PAPER NUMBER 1644 NOTIFICATION DATE DELIVERY MODE 12/18/2017 ELECTRONIC 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. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): mail@rkmllp.com EOfficeAction@rkmllp.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte HANS J. HANSEN, ZHENGXING QU, and DAVID M. GOLDENBERG Appeal 2017-011073 Application 13/114,122 Technology Center 1600 Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and TIMOTHY G. MAJORS, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1 under 35 U.S.C. § 134 involving a chimeric or humanized anti-CD74 antibody. The Examiner rejected the claims as failing to comply with the written description requirement, as anticipated, and as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. Statement of the Case Background “One of the major goals of immunotherapy is to harness a patient’s immune system against tumor cells or infectious organisms” (Spec. ^ 3). 1 Appellants identify the Real Party in Interest as Immunomedics, Inc. and identify related proceeding US 12/553,566 (2017-011312) (see App. Br. 2). Appeal 2017-011073 Application 13/114,122 “Induction of a T-lymphocyte response is a critical initial step in a host’s immune response. . . . T-cell activation requires an antigen-specific signal” (Spec. ^ 4). “This antigen-specific signal is usually in the form of an antigenic peptide bound either to a major histocompatibility complex (MHC) class I protein or an MHC class II protein” (Spec. ^ 4). “Class-II molecules are found on a limited number of cell types, primarily B cells” (Spec. ^ 5). “Murine LL1 (mLLl or murine anti-CD74 antibody) is a specific monoclonal antibody (mAb) reactive with CD74, the HLA Class-II-like antigen ... on the surface of B-lymphocytes” (Spec. ^ 7). “The present invention is directed to anti-CD74 antibodies and fragments thereof and antibody fusion proteins thereof, particularly chimeric, humanized or human antibodies, which can be rapidly internalized into a cell” (Spec. ^ 9). The Claims Claims 1, 2, 4-10, 14, 15, 22, 23, 26, and 29-35 are on appeal. Claim 1 is representative and reads as follows: 1. A chimeric or humanized anti-CD74 antibody or antigen- binding fragment thereof that binds to human CD74 and comprises human IgGl constant regions, wherein: (i) said anti-CD74 antibody or antigen-binding fragment thereof binds to the extracellular domain of CD74 of Raj i lymphoma cells in culture; (ii) said anti-CD74 antibody or antigen-binding fragment thereof is internalized by Raji lymphoma cells in culture; and (iii) said anti-CD74 antibody causes cell death of Raji cells in cell culture when crosslinked with goat antisera reactive with the Fc of a human IgG antibody. 2 Appeal 2017-011073 Application 13/114,122 The Issues A. The Examiner rejected claims 1, 2, 4-10, 14, 15, 22, 23, 26, and 29- 35 under 35 U.S.C. § 112, first paragraph as failing to comply with the written description requirement (Final Act. 2-8). B. The Examiner denied claims 1, 2, 4-10, 14, 15, 22, 23, 26, and 29-35 priority to US 10/377,122 (Final Act. 8). C. The Examiner rejected claims 1, 4, 7-10, 22, 23, 26, and 30 under 35 U.S.C. § 102(b) as anticipated by Rybak2 (Final Act. 8-10). D. The Examiner rejected claims 1, 2, 4-10, 22, 23, 26, 29-31, and 33 under 35 U.S.C. § 103(a) as obvious over Hansen,3 Leung,4 and Griffiths5 (Final Act. 11-12). E. The Examiner rejected claims 14, 15, 32, 34, and 35 under 35 U.S.C. § 103(a) as obvious over Hansen, Leung, Griffiths and Wrenn6 (Final Act. 12). F. The Examiner rejected claims 1, 2, 4-10, 22, 23, 26, 29-31, and 33 under 35 U.S.C. § 103(a) as obvious over Rybak, Leung, and Griffiths (Final Act. 12-13). 2 Rybak et al., WO 98/50435 Al, published Nov. 12, 1998. 3 Hansen et al., Internalization and catabolism of radiolabeled antibodies to the MHC class-II invariant chain by B-cell lymphomas, 320 Biochem. J. 293-300 (1996). 4 Leung et al., Construction And Characterization Of A Humanized, Internalizing, B-Cell (Cd22)-Specific, Leukemia/Lymphoma Antibody, LL2, 32 Molecular Immunology 1413-27 (1995). 5 Griffiths et al., US 5,728,369, issued Mar. 17, 1998. 6 Wrenn et al., WO 01/74402 A2, published Oct. 11, 2001. 3 Appeal 2017-011073 Application 13/114,122 G. The Examiner rejected claims 14, 15, 32, 34, and 35 under 35 U.S.C. § 103(a) as obvious over Rybak, Leung, Griffiths, and Wrenn (Final Act. 13). A. & B. 35 U.S.C. § 112, first paragraph and priority The Examiner finds “the only antibody disclosed in the specification which has said properties is humanized LL1” (Final Act. 3). The Examiner finds that “there is no disclosure in the specification as to what [other] CDRs . . . can be used in the claimed antibodies and yield antibodies with the properties recited in the claims . . . Thus, the skilled artisan cannot envision the detailed structure of the encompassed invention” {Id.). The Examiner also finds, regarding priority to US 10/377,122, that the “disclosure of the specification is not commensurate in scope with the functional limitation recited in the last three lines of claim one” (Final Act. V). The issues are: (i) Does the evidence of record support the Examiner’s finding that the antibody of claim 1 lacks descriptive support in the Specification? (ii) Does the evidence of record support the Examiner’s finding that the antibody of claim 1 lacks descriptive support in US 10/377,122? Findings of Fact 1. The Specification teaches: The humanized anti-CD74 monoclonal antibody (mAb) or fragment thereof comprise CDRs of a light chain variable region of a murine anti-CD74 mAb, that comprises CDR1 comprising an amino acid sequence RSSQSLVHRNGNTYLH (SEQ ID NO: 16), CDR2 comprising an amino acid sequence 4 Appeal 2017-011073 Application 13/114,122 TVSNRFS (SEQ ID NO: 17), and CDR3 comprising an amino acid sequence SQSSHVPPT (SEQ ID NO: 18). Further, the humanized anti- CD74 monoclonal antibody or fragment thereof comprises the heavy chain variable region of said humanized mAh that comprises CDRs of a heavy chain variable region of a murine anti-CD74 mAb, that comprises CDR1 comprising an amino acid sequence NYGVN (SEQ ID NO: 19), CDR2 comprising an amino acid sequence WINPNTGEPTFDDDFKG (SEQ ID NO:20), and CDR3 comprising an amino acid sequence SRGKNEAWFAY (SEQ ID NO:21). Further, the humanized mAb retains substantially the specificity for the CD74. (Spec. T| 62). 2. The Specification teaches “a combination of hLLl and anti- human IgG Fc specific Ab effectively caused cell death: >40% reduction in cell viability in one day and almost total cell death in 3 days. ... No such effect was observed with another internalizing Ab, hLL2, (humanized anti- CD22 Ab)” (Spec. T| 179). Principles of Law “[T]he asserted claims constitute a wish list of properties that a fully human, therapeutic TNF-a antibody should have: high affinity, neutralizing activity, and the ability to bind in the same place as the mouse A2 antibody.” Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341, 1351 (Fed. Cir. 2011). “The specification at best describes a plan for making fully-human antibodies and then identifying those that satisfy the claim limitations. But a ‘mere wish or plan’ for obtaining the claimed invention is not sufficient.” Id. While our precedent suggests that written description for certain antibody claims can be satisfied by disclosing a well- 5 Appeal 2017-011073 Application 13/114,122 characterized antigen, that reasoning applies to disclosure of newly characterized antigens where creation of the claimed antibodies is routine. . . . Claiming antibodies with specific properties ... can result in a claim that does not meet written description even if the [target] protein is disclosed because antibodies with those properties have not been adequately described. Id. at 1352. Analysis The central concern in both the written description and priority issues is the functional requirement in claim 1 that the humanized anti-CD74 antibody both binds to human CD74 and “causes cell death of Raji cells in cell culture when crosslinked with goat antisera reactive with the Fc of a human IgG antibody.” Written Description The functional requirement that the claimed antibody binds CD74 on Raji lymphoma cells, is internalized into Raji lymphoma cells, and causes cell death of Raji cells when crosslinked with antisera is the sort of wish list of properties which fails to satisfy the written description requirement since claiming “antibodies with specific properties, e.g., an antibody that binds to human TNF-a with A2 specificity, can result in a claim that does not meet written description even if the human TNF-a protein is disclosed because antibodies with those properties have not been adequately described.” Centocor, 636 F.3d at 1352. The absence of description in the Specification of a routine method for obtaining antibodies with the functional properties of claim 1 is evidenced by Example 9, where the specific hLLl anti-CD74 antibody with 6 Appeal 2017-011073 Application 13/114,122 a particular sequence as disclosed (FF 1) resulted in cell death while a humanized anti-CD22 antibody did not cause cell death (FF 2). There is, however, no disclosure in the Specification of what antibody structures, antigens, or other information are necessary to obtain the functional result of causing Raji cell death when crosslinked with goat antisera. Consequently, the instant “claims merely recite a description of the problem to be solved while claiming all solutions to it and, as in Eli Lilly and Ariad’s claims, cover any compound later actually invented and determined to fall within the claim’s functional boundaries-leaving it to the pharmaceutical industry to complete an unfinished invention.” Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co., 598 F.3d 1336, 1353 (Fed. Cir. 2010). The Specification provides insufficient description of the function of causing “cell death of Raji cells in cell culture when crosslinked with goat antisera reactive with the Fc of a human IgG antibody.”. While such effects were shown for the specific hLLl antibody (FF 2), the Specification fails to provide any structural or functional relationships for reliably, routinely or even rarely generating other antibodies which have the functional property of causing Raji cell death as required by claim 1. Appellants contend: “Conditions for culturing human cell lines are well known to persons skilled in the art. Information which is well known in the art need not be described in detail in the specification” (App. Br. 6). We find this argument unpersuasive because the issue is not whether the culture conditions can be reproduced, but rather whether the single species of anti-CD74 antibody disclosed in the Specification provides 7 Appeal 2017-011073 Application 13/114,122 sufficient descriptive support for the much larger functional genus recited in claim 1. Where a single specific inhibitor was taught by the Specification, Ariad holds that “a vague functional description and an invitation for further research does not constitute written disclosure of a specific inhibitor insufficient to satisfy the written description requirement.” Ariad, 598 F.3d at 1356. Similarly, in the instant case, the possession of a single species of antibody, without any structure or reliable methodology to produce other antibodies which necessarily share the functional property of causing “cell death of Raji cells in cell culture when crosslinked with goat antisera reactive with the Fc of a human IgG antibody” lacks written description. The Federal Circuit confronted comparable facts in Abb Vie, where the claim at issue was drawn to “a class of fully human antibodies that are defined by their high affinity and neutralizing activity to human IL-12.” AbbVie Deutschland GMBH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1299 (2014). Here, claim 1 is drawn to a class of antibodies with the ability to bind CD-74 and “cause cell death of Raji cells in cell culture when crosslinked with goat antisera reactive with the Fc of a human IgG antibody.” In AbbVie, representative examples were drawn to over two hundred structurally similar Joe-9 antibodies, while in the instant case sequences of just one human anti-CD74 were disclosed (FF 1). Id. at 1300. AbbVie noted the need to “describe representative antibodies to reflect the structural diversity of the claimed genus” and teaching that the binding affinity or “k0ff 8 Appeal 2017-011073 Application 13/114,122 rate is merely a desired result, rather than the actual means for achieving that result.” Id. at 1301. Similarly, the structural diversity of antibodies to epitopes, even epitopes of known sequence, is immense, and the functional results of ligands that have the dual properties of binding CD-74 while also causing “cell death of Raj i cells in cell culture when crosslinked with goat antisera reactive with the Fc of a human IgG antibody” is described without any specific and detailed guidance on means for routinely achieving the result provided by the Specification. The Examiner reasonably requires evidence, not currently provided by Appellants, of a structure-function correlation that is predictable and determinable as well as a reasonable number of species, necessary to demonstrate that “one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.” AbbVie, 759 F.3d at 1300. See Ariad, 598 F.3d at 1353 (The written description requirement guards against claims that “merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries.”). We note that our analysis addressing the functional clauses recited in claim 1 is less sweeping than that in Amgen Inc. v. Sanofi, 872 F.3d. 1367 (Fed. Cir 2017) where the Court found “the ‘newly characterized antigen’ test flouts basic legal principles of the written description requirement.” Amgen, 872 F.3d at 1378. We agree with the Examiner that under either the 9 Appeal 2017-011073 Application 13/114,122 AbbVie ox Amgen analysis, the instant disclosure is insufficient to satisfy the written description requirement. Priority Under 35 U.S.C. § 120, “in a chain of continuing applications, a claim in a later application receives the benefit of the filing date of an earlier application so long as the disclosure in the earlier application meets the requirements of 35 U.S.C. § 112, 1, including the written description requirement, with respect to that claim.” Tech. Licensing Corp. v. Videotek, Inc., 545 F.3d 1316, 1326 (Fed. Cir. 2008). Having already found that the instant application fails to satisfy the written description requirement for claim 1, we necessarily also find that the priority document in US 10/377,122 with identical description to that of the instant Specification also fails to satisfy the written description requirement. We recognize, but find unpersuasive, Appellants’ citation to the related appeal in US 11/676,466 (see App. Br. 9) because that appeal did not address the issue of written description in the context of Centcor, AbbVie, or Ariad. Unlike that appeal, the instant Examiner has addressed the claims as lacking descriptive support based on the coupling of a functional recitation of causing “cell death of Raj i cells in cell culture when crosslinked with goat antisera reactive with the Fc of a human IgG antibody” with no specific structural correlation. For the reasons already given, we agree with the Examiner that this claim lacks descriptive support. Consequently, we agree that the earlier priority document in US 10/377,122, which adds no additional structure-function relationship 10 Appeal 2017-011073 Application 13/114,122 information, fails to satisfy the written description requirement and therefore provide benefit of priority for the instant claim 1. Conclusion (i) The evidence of record supports the Examiner’s finding that the antibody of claim 1 lacks descriptive support in the Specification. (ii) The evidence of record supports the Examiner’s finding that the antibody of claim 1 lacks descriptive support in US 10/377,122. C. 35 U.S.C. § 102(b) over Rybak The Examiner finds Rybak teaches “humanized LL1 antibody/antibody fragment conjugates . . . The various functional attributes of the antibody recited in the claims are inherently found in the humanized LL1 antibody (aka because it is the same antibody as claims 20/21 of the instant application)” (Final Act. 8). The issue with respect to this rejection is: Does the evidence of record support the Examiner’s finding that Rybak anticipates the claims? Findings of Fact 3. Rybak teaches the “preferred antigens which bind to immunoglobulins of the invention are the CD22 and the CD74 cell surface marker” (Rybak 6:19-21). 4. Rybak teaches the “term ‘humanized’ refers to an antibody wherein the constant regions have at least about 80% or greater homology to human immunoglobulin. Additionally, some of the nonhuman, such as murine, variable region amino acid residues can be modified to contain amino acid residues of human origin” (Rybak 7:5-8). 11 Appeal 2017-011073 Application 13/114,122 5. Rybak teaches “LL2 or LL1 antibodies were conjugated to EDN as described above and assayed on Daudi or CA 46 Burkitt s lymphoma cells. []It is believed that LL1 and LL2 immunotoxins are delivered to the lysosomes where the immunotoxin is degraded to the antibody and RNase moieties” (Rybak 28:7-10). 6. Rybak claims a “pharmaceutical composition . . . wherein the antibody is selected from the group consisting of RFB4, LL1 and LL2” (Rybak 37, claim 26). 7. The Goldenberg Declaration7 states: “I am a named co- inventor of the subject matter disclosed in Rybak et al. (WO 98/50435). . . The Rybak publication discloses conjugating the murine LL1 mAh with EDN in Example 4” (Goldenberg Decl. ^ 4) and “Dr. Rybak could not have made or used humanized LL1 mAb and the Rybak publication does not disclose humanized LL1 mAb” {id. ^ 5). Principles of Law A prior art reference can only anticipate a claim if it discloses all the claimed limitations “arranged or combined in the same way as in the claim.” Wm. Wrigley Jr. Co. v. Cadbury Adams USALLC, 683 F.3d 1356, 1361 (Fed. Cir. 2012). “Inherency . . . may not be established by probabilities or possibilities. The mere fact that a certain thing may result from a given set of circumstances is not sufficient.” MEHL/Biophile Int 7. Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999). 7 Declaration of Dr. David M. Goldenberg, dated Oct. 26, 2014. 12 Appeal 2017-011073 Application 13/114,122 Analysis Appellants contend: The antibody in Rybak is not “the same antibody” as is presently claimed, because it is a murine antibody. Furthermore, no evidence or reasoned statement has been provided as to why a murine LL1 antibody would necessarily exhibit the characteristic of inducing cell death of Raj i cells in cell culture when cross-linked with goat antisera reactive with the Fc region of human IgG. (App. Br. 16). The Examiner responds: “Regarding the Goldenberg declaration under 37 CFR 1 .132, US Patent 6,653,104 (with a filing date of 11 /7/2001 and earlier priority dates) constitutes prior art disclosing and claiming the LL1 antibody. Goldenberg was an inventor of said application” (Ans. 17). We find that Appellants have the better position. Rybak provides no evidence that the LL1 antibody used in the examples is humanized (FF 5), nor that the claimed LL1 antibody is humanized (FF 6), and therefore Rybak’s LL1 antibody is reasonably read to encompass both murine and humanized LL1. The Goldenberg Declaration provides additional evidentiary support for our reasoning (FF 7). We find the Examiner’s reliance on US 6,653,104 unpersuasive because while the patent may claim the LL1 antibody (see US 6,653,104, claim 10), the Examiner does not identify any location where US 6,653,104 suggests that the claimed LL1 antibody is humanized. To the extent that US 6,653,104 or Rybak may suggest humanization of antibodies, there is no evidence that every, or even some humanized LL1 antibodies would satisfy the functional recitation in claim 1 of causing “cell death of Raji cells in cell 13 Appeal 2017-011073 Application 13/114,122 culture when crosslinked with goat antisera reactive with the Fc of a human IgG antibody.” Therefore, because Rybak neither expressly nor inherently teaches an antibody as recited by claim 1, we reverse this rejection. Conclusion The evidence of record does not support the Examiner’s finding that Rybak anticipates the claims. D. and E. 35 U.S.C. § 103(a) over Hansen, Leung, Griffiths and Wrenn Because these rejections turn on the same issue, we will consider them together. The Examiner finds Hansen teaches “the murine LL 1 antiCD74 antibody” but does not teach humanized antibodies (Final Act. 11). The Examiner finds Leung teaches “methods that could have been used to humanize said antibodies wherein the humanized antibody is IgGl” (id.). The Examiner finds Griffiths teaches conjugates (id.). The Examiner finds Wrenn teaches “CPT-11 (aka irinotecan) antibody conjugates and the advantages of such immunoconjugates” (Final Act. 12). The Examiner finds it obvious “to have created the claimed invention because Hansen et al. teach the murine LL1 antiCD74 antibody with the specificity recited in the claims and Leung et al. teach methods that could have been used to humanize said antibody wherein the humanized antibody is IgGl, whilst Griffiths et al. teach conjugates” (Final Act. 11). The issue with respect to this rejection is: Does the evidence of record support the Examiner’s conclusion that Hansen, Leung, Griffiths, and Wrenn render the claims obvious? 14 Appeal 2017-011073 Application 13/114,122 Findings of Fact 8. Hansen teaches: “Abs LL1, an IgGi, and LL2, an IgG2a reacting with CD22, have previously been described . . . LL1 was previously described as reacting with a class-II-like molecule, but, as demonstrated here, it reacts with a cell-surface-expressed epitope of the Ii subunit. Other Abs to Ii (CD74) were LN2” (Hansen 293, col. 2 to 294, col. 1; citations omitted). 9. Leung teaches “the successful humanization of an internalizing murine MAb, LL2, which recognizes CD22 . . . Humanized LL2, therefore, could be an important reagent for diagnosing and treating patients with leukemias or lymphomas of B-cell lineage” (Leung 1414, col. 1). 10. Leung teaches “the three-dimensional structures for both the murine (mLL2) and humanized (hLL2) MAbs were ‘modeled-by- homology’” (Leung 1414, col. 2). 11. Griffiths teaches: “Carefully controlled reduction of antibodies results in preferential reduction of disulfide bonds on the hinge region of the antibody, and the resulting cysteine residues can then be used for the conjugation reaction” (Griffiths 11:22-26). 12. Wrenn teaches the camptothecin (CPT) irinotecan {see Wrenn 4:25) and that “antibodies may be conjugated to the CPT in a conventional manner” (Wrenn 14:22). 13. The Goldenberg Declaration states: The LL1 hybridoma was not provided to the Garden State Cancer Center (GSCC) at the Center for Molecular Medicine and Immunology or to the National Cancer Institute (NCI) in the performance of the studies described in Hansen. A limited amount of the murine LL1 monoclonal antibody (mAb) 15 Appeal 2017-011073 Application 13/114,122 specifically for the collaborative studies was provided to the GSCC . . . Therefore, the control of murine LL1 mAh at GSCC was under my supervision ... No murine LL1 mAb was provided to the Hansen co-authors, Anita Valdez and Paul A. Roche, from NCI. (Goldenberg Decl. ^ 3). Principles of Law [Djuring patent prosecution, an examiner is entitled to reject claims as anticipated by a prior art publication or patent without conducting an inquiry into whether or not that prior art reference is enabling. As long as an examiner makes a proper prima facie case of anticipation by giving adequate notice under § 132, the burden shifts to the applicant to submit rebuttal evidence of nonenablement. In re Antor Media Corp., 689 F.3d 1282, 1289 (Fed. Cir. 2012). Analysis Appellants contend “the LL1 hybridoma was never made publicly available and that the murine LL1 mAb was never made publicly available” and that “Hansen does not disclose the sequences of the murine LL1 antibody which Leung’s methods could be used to humanize the murine LL1 antibody” (App. Br. 18). Appellants contend an “artisan would have been unable to construct a chimeric or humanized antibody with the claimed properties without the knowledge of murine LLl’s CDRs and specific properties or a publicly available source of the murine LL1 producing hybridoma upon which the techniques of Leung and Griffiths could have been applied” {id.). 16 Appeal 2017-011073 Application 13/114,122 The Examiner responds Based on the teachings of Hansen et al., a routineer could have created an antibody with the functional attributes recited in the claims. Whilst Hansen et al. do not teach humanized antibodies thereof, Leung et al. teach methods that could have been used to humanize said antibodies wherein the humanized antibody is IgGl (Ans. 18). We find that Appellants have the better position.8 While the Examiner may initially shift the burden, the Goldenberg Declaration provides evidence, currently unrebutted, that Hansen lacked both access to the LL1 antibody and lacked the sequence of the LL1 antibody (FF 13). We recognize, but find unpersuasive, the Examiner’s argument that the “amino acid sequence of an antibody can be determined from the antibody itself using routine experimentation” (Ans. 17). While this is certainly true, the Goldenberg Declaration expressly states that LL1 recipients “could not use the murine LL 1 mAh for other purposes than the collaborative studies or share the murine LL 1 mAh with others that were not under her control” (Goldenberg Decl. ^ 5; cf FF 13). Thus, there is insufficient evidence showing that the antibody was available for amino acid sequencing. 8 We note that the Examiner has provided no evidence that the Goldenberg patent was prior art required to submit a deposit of the LL1 murine antibody for enablement {see, e.g., MPEP § 2164.06(a)(II)) and that the requirement resulted in a deposit that satisfied the Budapest treaty requirements of 37 C.F.R. § 1.806. 17 Appeal 2017-011073 Application 13/114,122 Without legal access to the LL1 hybridoma and antibody, and without knowledge of the LL1 antibody amino acid or nucleic acid sequence, the ordinary artisan familiar with Hansen and Leung would not have reasonably been enabled to synthesize a humanized form of LL1 (FF 13). That is, as Leung explains, a process for humanizing the LL2 monoclonal antibody may be performed by homology analysis, which requires either the amino acid or nucleic acid sequence of the starting murine antibody (FF 10). Because Hansen, Leung, Griffiths, and Wrenn lacked access to the LL1 antibody or hybridoma in order to generate an amino acid or nucleic acid sequence, the homology analysis process of Leung would not have been capable of being performed. Therefore, while we agree with the Examiner that the prior art teaches and enables synthesis of a generic chimeric or humanized anti-CD74 antibody (FF 8-11), we disagree that the prior art teaches and enables synthesis of the specific chimeric or humanized LL1 antibody. This distinction is important, because the Examiner noted it is “unclear/unpredictable as to what antibodies other than humanized LL 1 would have such properties” (Ans. 3), specifically referring to the functional requirement that “the anti-CD74 antibody causes cell death of Raj i cells in cell culture when cross-linked with goat antisera reactive with the Fc region of human IgG” in claim 1. We also find this functional limitation unpredictable for humanized antibodies, in the absence of evidence that other humanized antibodies would necessarily share this functional capacity. “Inherency . . . may not be established by probabilities or possibilities. The mere fact that a certain 18 Appeal 2017-011073 Application 13/114,122 thing may result from a given set of circumstances is not sufficient.” MEHL/BiophileInt’l. Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999). In this case, even if the ordinary artisan generated a chimeric or humanized anti-CD74 antibody following the guidance of the prior art, it is not inherently necessary, or even proven likely on the evidence currently of record, that this antibody will function to cause “cell death of Raji cells in cell culture when cross-linked with goat antisera reactive with the Fc region of human IgG” as required by claim 1. Conclusion of Law The evidence of record does not support the Examiner’s conclusion that Hansen, Leung, Griffiths, and Wrenn render the claims obvious. D. 35 U.S.C. § 103(a) over Rybak, Leung, Griffiths, and Wrenn Appellants contend, as in the rejection relying upon Hansen, that the person of ordinary skill “would have been unable to construct a chimeric or humanized antibody with the claimed properties without the knowledge of the murine LLl’s CDRs and specific properties or a publicly available source of the murine LL1 producing hybridoma, upon which the techniques of Leung and Griffiths could have been applied” (App. Br. 21). The Examiner responds “Rybak et al. teaches the murine LL1 and the humanized LL1 antibody wherein the murine antibody could also be humanized as per the art recited in the instant rejection” (Ans. 20). We find Appellants have the better position for the reasons given above. Rybak provides no disclosure regarding the amino acid or nucleic acid sequence of the LL1 antibody (FF 5-6). The Goldenberg Declaration 19 Appeal 2017-011073 Application 13/114,122 provides evidence that Rybak lacked permission to sequence LL1 and would therefore have been unable to generate a humanized LL1 antibody using the homology method of Leung (FF 7). Consequently, Appellants have rebutted the enablement of the prior art for synthesizing a humanized form of the LL1 antibody with the functional requirements of claim 1 and we therefore reverse this rejection. SUMMARY In summary, we affirm the rejection of claim 1 under 35 U.S.C. § 112, first paragraph as failing to comply with the written description requirement. Claims 2, 4-10, 14, 15, 22, 23, 26, and 29-35 fall with claim 1. We affirm the Examiner’s denial of priority for claims 1, 2, 4-10, 14, 15, 22, 23, 26, and 29-35 to US 10/377,122. We reverse the rejection of claims 1, 4, 7-10, 22, 23, 26, and 30 under 35 U.S.C. § 102(b) as anticipated by Rybak. We reverse the rejection of claims 1, 2, 4-10, 22, 23, 26, 29-31, and 33 under 35 U.S.C. § 103(a) as obvious over Hansen, Leung, and Griffiths. We reverse the rejection of claims 14, 15, 32, 34, and 35 under 35 U.S.C. § 103(a) as obvious over Hansen, Leung, Griffiths and Wrenn We reverse the rejection of claims 1, 2, 4-10, 22, 23, 26, 29-31, and 33 under 35 U.S.C. § 103(a) as obvious over Rybak, Leung, and Griffiths. We reverse the rejection of claims 14, 15, 32, 34, and 35 under 35 U.S.C. § 103(a) as obvious over Rybak, Leung, Griffiths, and Wrenn. 20 Appeal 2017-011073 Application 13/114,122 No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 21