11493132 (P.T.A.B. Oct. 10, 2018)

Ex Parte Grosmaire et al

Patent Trial and Appeal BoardOct 10, 2018

11493132 (P.T.A.B. Oct. 10, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 11/493, 132 07/25/2006 109041 7590 10/12/2018 Cooley LLP / Emergent 1299 Pennsylvania Ave., N.W. Suite 700 Washington, DC 20004-2400 FIRST NAMED INVENTOR Laura S. Grosmaire 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 ATTORNEY DOCKET NO. APV0-012/03US 327714-2167 CONFIRMATION NO. 8168 EXAMINER SCHWADRON, RONALD B ART UNIT PAPER NUMBER 1644 NOTIFICATION DATE DELIVERY MODE 10/12/2018 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): zIPPatentDocketingMailbox US @cooley.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte LAURA S. GROSMAIRE, MARTHA S. HAYDEN- LEDBETTER, JEFFREY A. LEDBETTER, PETER A. THOMPSON, SANDY A. SIMON, and WILLIAM BRADY Appeal2017-006468 Application 11/493, 132 Technology Center 1600 Before DEMETRA J. MILLS, ULRIKE W. JENKS, and TIMOTHY G. MAJORS, Administrative Patent Judges. JENKS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. Â§ 134(a), Appellants 1 appeal from the Examiner's decision to reject claims as being directed to non-statutory subject matter. We have jurisdiction under 35 U.S.C. Â§ 6(b). We REVERSE. 1 Appellants identify the real party in interest as Aptevo Research and Development LLC. Br. 2. Appeal2017-006468 Application 11/493, 132 STATEMENT OF THE CASE Claims 118, 122, 126, 133, 135-138, 141, 142, 154, and 157-159 are on appeal, and can be found in the Claims Appendix of the Appeal Brief. Br. 25-30. Claim 118 is representative of the claims on appeal, and reads as follows: 118. A humanized or chimeric CD37-specific immunoglobulin binding protein, comprising: (a) a light chain variable region comprising, from amino terminus to carboxy terminus, a first framework region, a light chain CDRl comprising the amino acid sequence set forth in SEQ ID NO: 61, a second framework region, a light chain CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 64, a third framework region, a light chain CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 66, and a fourth framework region; and (b) a heavy chain variable region comprising, from amino terminus to carboxy terminus, a first framework region, a heavy chain CDRl comprising the amino acid sequence set forth in SEQ ID NO: 63, a second framework region, a heavy chain CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 65, a third framework region, a heavy chain CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 69, and a fourth framework region; wherein the binding protein binds human CD37. The other independent claims, claims 122 and 126, recite different heavy chain CDR3 sequences. Appellants request review of Examiner's rejection under 35 U.S.C. Â§ 112, first paragraph as lacking sufficient descriptive support for the claims. 2 Appeal2017-006468 Application 11/493, 132 Examiner finds that the claims contain new matter that is not sufficiently supported by the Specification as filed. Specifically, according to Examiner "[ t ]here is no support in the specification as originally filed for the protein of claim 118 absent the limitation that said protein is a humanized SMIP [ ( small, modular immunopharmaceuticals)] or a chimeric SMIP of SEQ. ID. N0:2." Ans. 2. Does the preponderance of evidence on this record support Examiner's finding that Appellants' Specification fails to provide written descriptive support for the claimed invention? Findings of Fact FF 1. Specification as originally filed discloses using CD3 7-specific binding molecules. Spec. ,r 2, compare e.g. claims 2, 12 (CD37-specific small, modular immunopharmaceuticals (SMIPs)) with originally filed claims 1, 11, 28, 33 ("CD37-specific binding molecules"), claims 29, 3 5 ("CD3 7-specific antibodies"). "The CD3 7-binding molecules according to the invention describe structures (binding domains derived from antibodies, hinge variants, CH2CH3 regions being the same or different, and various isotypes)." Id. ,r 181. FF2. Specification teaches humanized binding molecules: "Humanization" is expected to result in an antibody that is less immunogenic, with complete retention of the antigen-binding properties of the original molecule. In order to retain all of the antigen-binding properties of the original antibody, the structure of its antigen binding site should be reproduced in the "humanized" version. This can be achieved by grafting only the nonhuman CDRs onto human variable framework domains and constant regions, with or without retention of critical framework residues ... or by recombining the entire nonhuman variable domains ( to 3 Appeal2017-006468 Application 11/493, 132 preserve ligandbinding properties), but "cloaking" them with a human-like surface through judicious replacement of exposed residues (to reduce antigenicity). Spec. ,r 271. "[H]umanization by CDR grafting involves recombining only the CD Rs of a non-human antibody onto a human variable region framework and a human constant region." Id. ,r 272. "The framework residues that need to be preserved are amenable to identification through computer modeling." Id. ,r 273. FF3. Specification describes SMIPs as: novel binding domain-immunoglobulin fusion proteins that generally feature a binding domain for a cognate structure such as an antigen, a counterreceptor or the like, an IgG 1, IGA or IgE hinge region polypeptide or a mutant IgG 1 hinge region polypeptide having either zero, one or two cysteine residues, and immunoglobulin CH2 and CH3 domains. Spec. ,r 57. "SMIPs are capable of ADCC and/or CDC but are compromised in their ability to form disulfide-linked multimers." Id. i158. FF4. Specification discloses "humanized CD37-specific SMIP polypeptides that exhibit at least 80 percent identity to the polypeptide set forth in SEQ ID NO: 2." Id. ,I 59; see id. ,I 64. SEQ ID NO: 2 is a non- humanized sequence. See id. at 277. [H]umanized CD37-specific SMIP polypeptides comprising a CDRl, a CDR2, and a CDR3, that exhibits at least 80 percent identity to the polypeptide set forth in SEQ ID NO: 2. Such CD37-specific SMIP polypeptides may further comprise a human framework domain separating each of CDRl, CDR2, and CDR3. Id. ,I 73. 4 Appeal2017-006468 Application 11/493, 132 FF5. Specification discloses Fig. 30A L-FR2 1 49 Q16_ -_G26-1 DIQf>!TQSP.A.SLSJISVGl:'lVflTC RTSEN\IYSYL.\ WYQQKQGKS~Ll \IS l!Ol6,_-_01W01 Â£IVL TQ.SP.ATlSLSl'GÂ£RA1lSC RTSÂ£1f.'YSYLA W'l'(!QKPGQ.11.f'RLLIY (or,5~.risu,; I T(l:SPA LS S GI: T C RTSHNYSYLA WYQQ.K G P LL I L--CDRe L-FR:l L-CTJR3 SQ 97 Q16_ - _Gn -1 fAl(TI.Jl.[ GV~SlFSGSGSGTqFsu-:rssL~N:0%SYf.C Q!Hl5DNPWT t!Ol& â€¢. - .. 019001 FIUCTlA.Â£ GIPARFSGSG'iGTDFTl TISSl[l'EOFAVYYC QHHSONPWT C0'1senrns !'Mn.<\Â£ G P RFSG%%1 F L I55L PED Y C QHHSONPWT LÂ·-Ff.:'4 (G4S}3 hnker H-rll1 9g 1 50 C:16 -Â· 628-1 FGGGTI'.Lf!K <'.iGGGSGG>.>GSGGGGSS AVQLQQSGPESHPGASVHSCKA'.iGYS~T H016_.Â°:: __ 019001 FG:l;GTKIIHK GGGGS:G"'*S<:i<:iGGTG EVQLVQSG.AÂ£\/KKl'GÂ£SLKISCKGSGY5FT Consem;w; FG GT tIK GGGG5~'><..(;--{',G \i<~L QSG F. Kf>G S USCK S-GYSFT li-COR1 t-i'-r:~;: HÂ·<.OR2 31 76 Ol.6_ - _G2B-l GYNMN WVKQN!iGKSLEW1G NlDPYl'Gt.iTTYli!i:KFKG KA Tl T\,'!))($$5 H01LÂ·_Ol!I001 G'0Â»1~ l'<'VRQ-"lPGKG!..!:W>lG flIDPn,;.;.;TIYNRKFKG QvrISADKSIS: Con~~nius G'l\\l,',1N W>I Q GK lÂ£W G IHC>PYYGGTIYllRl'.Fl:"../YS'l1.,A ltlYQQKt"'(~Q.:t~~p.:Hf.JLIY EtV1,TQS?i<'.,'1'J:,SY..SPGER.r...'l'LSC F.Asi:-:NVYSYLA 1,rtQrJ.KPGQAPRLLIY F..IVLTQÂ·S?A?LSLSPG!:c:Rl<.'l'LSC RTS!rn-:\.;y SYL,A WYQQK PGQAPRU.-I Y CDR2 ..â€¢. _ .....â€¢ , , â€¢. FR} ..â€¢ , ....â€¢â€¢ , â€¢ . â€¢ . .. .... CDR3 ..... rn4 .. - f'A.K"1'LA.E G.lPARf SGSGSGTDFTLTI SSLEPEDFAVYYC Q,U{SDNPWT FQQG'.l'K\iE IK FA.K'I'LAE G.LPtiR.FSCSGS.GTOfTLTÂ·r SSLEPEDF.~ .. v~~lYC QHHS!)NPt-;Â·T S. . GQGÂ·l1K\J'BIK f/\KTLAB. GJ:PARFSGSGSGTDFTL'.rISSLEPBDF,>.VYYC QHf!SDNPWT' f'G\;)G'l'KVEIK 5 Appeal2017-006468 Application 11/493, 132 HEAVY C:Hl'.s"IN ..â€¢.â€¢ , â€¢â€¢ , . , â€¢.â€¢ FRl. . . . . . . . . . â€¢ . . CDRl ..... FR2 ...... . 019 0<11. f'.\lQLVQSGiU:\/K:Kf'GESLK T SCKGSGYSFT ,'";YNMN '-',lVRQMPGKGLE\'(111!'.; 019 044 gvr,JL"/QSGA}";VHK"f~GESLK I SCKGSGYSFT GYl'JfÂ·1N v~~\t.RQMPGKGL.Bi-.J'r-JG 019001 Â£VQL'..i't)SGAÂ£Vi:S1,K l SCKGSGYS::''T GY~'.JNN l~'VRQMP(::'..KGL.i:WMG 019041 019044 019()01 019041 0190\'lll. 019001 .. , , , ... , , ..â€¢. , ... FR3 .... , ........ . NIDPYYGGTTYNRKFKC QVTISADKSISTAYLQWSSLKA.SDTAMYYCA.R NIDPY'tGC'rTYNRKfKC QVT1SADKS1 STAYLQWSSLKAStl'lV,.M:i:'YCA.R N!O:PYYGGT'I'"ft-!R.KfKG OV'f'1SAt1KS15TAYLQWSSLKAS0'1'AM'.x'YCAR -C'.DR}_ ..... FF.A ... SVG.PF!)Y ~,~G1J(?"J:L\'Pl'VSS SV~Jp:rÂ·t:Â·S ~'iG~~"l"LVT1'v'SS SVGPM.DY WGRG'I'LVTVSS FAST A formatted DNA and amino acid sequence alignments of three humanized constructs of TRU-016 (019001, 019041, and 019044) are shown in Figure 32. Spec. ,r 279. Principle of Law [T]he hallmark of written description is disclosure. . . . [T]he test requires an objective inquiry into the four comers of the specification from the perspective of a person of ordinary skill in the art. Based on that inquiry, the specification must describe an invention understandable to that skilled artisan and show that the inventor actually invented the invention claimed. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010). Analysis Examiner finds that "all of the sequences recited in the claims are found only in the context of the ... SMIP constructs." Ans. 4 ( emphasis removed). Examiner finds that "Appellant[ s are] broadening the disclosure of the specification by omitting limitations recited the specification in the context of the claimed subject and also creating a new subgenus not disclosed in the specification as originally filed." Id. at 6 (emphasis removed). According to Examiner "there is no disclosure in the 6 Appeal2017-006468 Application 11/493, 132 specification of the production of chimeric or humanized nonSMIP proteins with the sequences recited in the claims." Id. Appellants contend that antibody engineering at the time of filing was well known and was understood that antigen-binding required a structural and functional relationship between six intact complementary determining regions (CDRs). Br. 5. "SMIPs are exemplary binding molecules that, like full-sized antibodies and scFvs, bind to a particular target via CDRs of variable heavy and light chains." Id. at 6. Appellants contend that the claims recite specific sequences for the six CDR's and provides the location of the CD R's in relation to the framework regions. Id. at 11. Appellants additionally contend that the Specification recites broad language which omits the feature that the Examiner alleges is critical. Id. at 14. Claim 118 recites a "humanized or chimeric CD3 7-specific immunoglobulin binding protein" having heavy and light chains containing the following structures SEQ ID NO: 61, 63---65, 66, and 69, all of which are needed for binding the identified target CD37. Br. 25 (Claims Appendix). In addition, the claim also provides the requisite position of these sequences in the heavy and light chain. From the preamble the claim requires a protein that resembles the structure of an immunoglobulin, i.e. antibody. The body of the claim recites particular features of this immunoglobulin binding protein structure. Specifically, the body of the claim recites that the requisite CDR sequences needed for binding the antigen. The claim, therefore, has the following constraints: the structure is a protein, the protein needs to look like an immunoglobulin, the protein needs to have the recited sequences in a particular order, and additionally the protein needs to bind an antigen, specifically CD37. 7 Appeal2017-006468 Application 11/493, 132 We find that on this record Appellants have the better position. Here, on its face the Specification as filed disclosed that CD37-specific binding molecules encompass not only the SMIP (small, modular immuno pharmaceuticals) exemplified in the Specification but also encompasses more generic CD37-specific binding molecules as well as CD37-specific antibodies, also known as immunoglobulins. FF 1. Thus, we are not persuaded by Examiner's position that the recitation of CD37-specific immunoglobulin binding proteins as recited in the preamble of the claim constitutes new matter because the Specification as originally filed is not limited to the exemplified SMIPs. We next determine whether the Specification provides sufficient descriptive support to convey Appellants' possession of the genus of CD37- specific immunoglobulin binding molecules as claimed. The Specification, "preferably omits from the disclosure any routine technology that is well known at the time of [the] application." Chiron Corp. v. Genentech, Inc., 363 F.3d 1247, 1254 (Fed. Cir. 2004) (citations omitted); Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005) ("[t]he descriptive text needed to meet these requirements varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence."). Here, the Specification provides that the antigen CD37 is known and the antigen-binding properties, i.e. the complementary determining regions (CDRs), are identified. Spec. ,r 6; FF5 and FF6. The Specification explains that the process of humanizing a binding molecule the nonhuman CDRs are grafted onto human variable framework domains and constant regions. FF2. In other words, the claims provide relevant identifying characteristics that describe the immunoglobulin binding protein. Specifically, the claims 8 Appeal2017-006468 Application 11/493, 132 identify sequences that are arranged in a particular order, to resemble the structure of an immunoglobulin that binds an identified target, namely CD37. The requirements of what constitutes sufficient written description for an antibody antigen interaction has evolved. [T]he written description requirement can be met by "show[ing] that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics ... i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics." Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002) ( emphasis omitted, alterations in original). Under Noelle "as long as an applicant has disclosed a 'fully characterized antigen,' either by its structure, formula, chemical name, or physical properties, or by depositing the protein in a public depository, the applicant can then claim an antibody by its binding affinity to that described antigen." Noelle v. Lederman, 355 F.3d 1343, 1349 (Fed. Cir. 2004). In Amgen, the Federal Circuit held that the "newly characterized antigen" test[ 2] flouts basic legal principles of the written description requirement. Section 112 requires a "written description of the invention." But this test 2 "'[ A ]nalogizing the antibody-antigen relationship to a 'key in a lock,"' it was more apt to analogize it to a lock and "a ring with a million keys on it."' Amgen Inc. v. Sanofi, 872 F.3d 1367, 1377 (2017) (citing Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011)). 9 Appeal2017-006468 Application 11/493, 132 allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen. Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378 (2017). Thus, Amgen explains that it is not sufficient to arrive at a conclusion of having adequate written description for a product based on the ability to make and use it. Id. Amgen leaves open, however, the possibility that "a functional genus claim to corresponding antibodies, is one in which the underlying science establishes that a finding of 'make and use' (routine or conventional production) actually does equate to the required description of the claimed products," and such a showing may be sufficient to establish adequate written description. Id. On this record, the Specification not only provides us with information with respect to the antigen (see Spec. ,r 6), the Specification also describes that specific CDR sequences must be present in order to meet the claim limitation of binding CD37. It is the CDR sequences that contact the antigen and provide the specificity for the binding protein, i.e. antibody, to a particular antigen. Here, the Specification and claims provide sequences that contain the CDRs structures critical for binding the antigen CD37. See FF5 and FF6; see also Br. 5 ("in the field of antibody engineering, the structure-function relationship between six intact complementarity determining regions (CDRs) and antigen binding activity was well known such that at the time of filing"). The Examiner's position is that the Specification discloses binding proteins only in the context of SMIPs and not in the broader immunoglobulin binding proteins now claimed. See Ans. 6 ("chimeric or humanized nonSMIP"). The Specification explains that these SMIP structures are fusion proteins that contain the binding domain of an antigen 10 Appeal2017-006468 Application 11/493, 132 and also retain other immunoglobulin characteristics. FF3. The Specification provides that in humanizing an antibody the goal is to make it less immunogenic, but in the process it is important to maintain the ligand binding properties and only change those portions of the molecule that are exposed. FF2; see Br. 18. Emphasis on a minimized structure would not detract from the broader teaching in the Specification that the structures were originally derived from larger molecules, and that it was known at the time of filing that the CD Rs can be placed on other frameworks. See Br. 19 ("using the disclosed CDR sequences in the context of framework regions, onto other scaffolds to form CD37-binding molecules"); FF2. The Specification provides sufficient description of the amino acid residues necessary to interact between the binding protein and the known antigen CD37. FF5 and FF6. Because these claimed binding proteins are immunoglobulin binding proteins they are further limited by structural constraints, specifically, that the claimed molecules resemble an immunoglobulin structure. Here, the Specification, and more importantly the claims, describe the amino acid residues involved in the antigen-binding protein interaction, as well as the position of these critical residues in the structure of the binding protein frame work. See FF5 and FF6. The recited CDR sequences, therefore, identify sufficiently which keys from the millions of keys on the ring would fit the CD37 lock. We find that the recitation of the CDR sequences and their positional information within the framework in conjunction with the characterized antigen to which the CDR sequences bind provides sufficient descriptive support for a genus of immunoglobulin binding proteins that contain these sequences as claimed. 11 Appeal2017-006468 Application 11/493, 132 Appellants' Specification (reciting SEQ ID NO: 61 and 63---69) provide sufficient descriptive details regarding the CDRs sequences needed to maintain the binding to CD37. See FF5 and FF6; see generally Br. 16. Because the preponderance of the evidence does not support Examiner's rejection for failure to comply with the written description requirement, we reverse. SUMMARY We reverse the rejection of all claims. REVERSED 12