DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application, Amendments and/or Claims
The amendment of 10 August 2022 has been entered in full. Claims 3, 5, 6, 9, 11, 13, 16, 17, 19, 22, and 23 are amended.
Claims 1-24 are under consideration in the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01 November 2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
1. Claims 1-24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
1a. Claims 1-24 are rejected as vague and indefinite for reciting the term “29E4B5” as the sole means of identifying the antibody/hybridoma recited in the instant claims. It is well known in the art that accession numbers and catalog numbers can be altered, deleted, amended, or revised over time by various inventors and companies. Furthermore, the use of laboratory designations only to identify a particular molecule renders the claims indefinite because different laboratories may use the same laboratory designations to define completely distinct molecules. Hence, one of ordinary skill in the art would not be unable to discern the metes and bounds of the claimed invention.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
2. Claims 1-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites an isolated antibody, which binds a single-chain variable fragment (scFv) consisting of the amino acid sequence of SEQ ID NO: 1, wherein the antibody binds the same epitope of the scFv as antibody 29E4B5 or competes against antibody 29E4B5 for binding to the scFv.
Claim 3 recites that the antibody comprises the same heavy chain complementary determining regions and the same light chain complementary determining regions as antibody 29E4B5. Claim 4 recites that the antibody comprises the same VH and the same VL as antibody 29E4B5. Claims 6-10 also recite nucleic acids encoding the antibody, vectors, and host cells.
The specification of the instant application teaches that mice are immunized with a “FMC63-scFv” protein comprising an artificial signal peptide, an anti-CD19 scFv fragment consisting of the amino acid sequence of SEQ ID NO: 1, and a His-tag (pages 25-26, Example 1; page 27, Example 2). It is noted that the amino acid sequence of SEQ ID NO: 1 is 245 amino acids in length. The specification teaches that hybridomas are eventually selected and subcloned and monoclonal hybridomas are expanded (pages 29-30). The specification indicates subclones from “29E4” (including 29E4B5) have superior binding to anti-CD19 CAR+ T cells (page 30, last paragraph; page 30, Table 5). The specification discloses that the variable regions of the mouse anti-HMC63-scFv monoclonal antibody 29E4B5 are sequenced (page 32-34). Table 7 at page 33 lists the amino acid sequences of the anti-scFv antibody 29E4B5.
However, the instant claims only recite an antibody that binds the same epitope of the scFv as antibody 29E4B5 or competes against antibody 29E4B5 for binding to the scFv (and nucleic acids encoding such antibody). The teachings of the specification are not adequate written description of an entire genus of antibodies that (i) bind a scFv consisting of the amino acid sequence of SEQ ID NO: 1, (ii) bind the same epitope of the scFv as antibody 29E4B5, or (iii) compete against antibody 29E4B5 for binding to the scFv. The first paragraph of 35 U.S.C. § 112 "requires a 'written description of the invention' which is separate and distinct from the enablement requirement." Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991). An adequate written description of a chemical invention "requires a precise definition, such as by structure, formula, chemical name, or physical properties." University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004); Regents of the Univ. of Cal. v. Eli Lilly & Co., Inc., 119 F.3d 1559, 1566 (Fed. Cir. 1997); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993). "A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F.3d at 923; Eli Lilly, 119 F.3d at 1568. Instead, the "disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described." Id. In addition, possession of a genus "may be achieved by means of a recitation of a representative number of [compounds]... falling within the scope of the genus." Eli Lilly, 119 F.3d at 1569. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus. See Rochester, 358 F.3d at 927.
Thus, case law dictates that to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include actual reduction to practice, disclosure of drawings or structure chemical formulas, sufficient relevant identifying characteristics (such as, complete or partial structure, physical and/or chemical properties, and functional characteristics when coupled with a known or disclosed structure/function correlation), methods of making the claimed product, level of skill and knowledge in the art, predictability in the art, or any combination thereof. In the instant case, the only factors present in the claims are (i) a structural characteristic of an antibody and (ii) functional characteristics of binding a scFv consisting of the amino acid sequence of SEQ ID NO: 1, binding the same epitope of the scFv as antibody 29E4B5, and competing against antibody 29E4B5 for binding to the scFv. There is no other identification of any particular sequence or structure of the antibody in the instant claims. There is also no identification of any particular sequence or structure that must be conserved in order to provide the required functions of binding a scFv consisting of the amino acid sequence of SEQ ID NO: 1, binding the same epitope of the scFv as antibody 29E4B5, and competing against antibody 29E4B5 for binding to the scFv.
Thus, the claims are drawn to a genus of antibodies that (i) bind a scFv consisting of the amino acid sequence of SEQ ID NO: 1, (ii) bind the same epitope of the scFv as antibody 29E4B5, and (iii) compete against antibody 29E4B5 for binding to the scFv. In this case, the specification fails to disclose and there is no art-recognized correlation between structure of the genus of antibodies and the required functions recited by the claims. In other words, the specification does not teach the structure (i.e., heavy and light chain variable domains or CDRs) which results in an antibody that binds a scFv consisting of the amino acid sequence of SEQ ID NO: 1, binds the same epitope of the scFv as antibody 29E4B5, and competes against antibody 29E4B5 for binding to the scFv.
The description of one monoclonal antibody, termed “29E4B5”, that binds to the anti-CD19 scFv consisting of the amino acid sequence of SEQ ID NO: 1 (see specification page 33, Table 7) is not adequate written description of an entire genus of antibodies that bind a scFv consisting of the amino acid sequence of SEQ ID NO: 1, bind the same epitope of the scFv as antibody 29E4B5, and compete against antibody 29E4B5 for binding to the scFv. Applicant is reminded that generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus (Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956 (Fed. Cir. 2002); Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997); MPEP §2163(II)(3)(a)(ii))). A patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). See also AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
The instant claims are attempting to claim every antibody that would achieve a desired result, i.e., binding an anti-CD19 scFv consisting of the amino acid sequence of SEQ ID NO: 1, binding the same epitope of the scFv as antibody 29E4B5, and competing against antibody 29E4B5 for binding to the scFv, whereas the specification does not describe representative examples to support the full scope of the claims. Applicant is reminded that "when a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the same result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)). However, in the instant case, the specification does not disclose the generation of a genus of antibodies that (i) bind a scFv consisting of the amino acid sequence of SEQ ID NO: 1, (ii) bind the same epitope of the scFv as antibody 29E4B5, and (iii) compete against antibody 29E4B5 for binding to the scFv. Therefore, the specification does not provide adequate written description of an entire genus of antibodies that achieve a desired result, i.e., binding a scFv consisting of the amino acid sequence of SEQ ID NO: 1, binding the same epitope of the scFv as antibody 29E4B5, and competing against antibody 29E4B5 for binding to the scFv.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “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. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed” (See page 1117). See also, Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (See Vas-Cath at page 1116). A “mere wish or plan” to obtain the claimed invention is not sufficient (Centocor Orth Biotech, Inc. v. Abbott Labs, 636 F.3d 1341 (Fed. Cir. 2011); Regents of the Univ. of California, 119 F.3d at 1566). In the instant application, the skilled artisan cannot envision the detailed chemical structure of the antibodies (and nucleic acids encoding such) of the encompassed product and method claims, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. It is also noted that as in Amgen, instant independent claim 1 attempts to describe a genus of antibodies by describing something that is not an antibody, i.e. the epitope to which the antibody binds. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The antibody is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. It is well-known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope. For example, Lloyd et al. teach that over hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Lloyd et al. Protein Engineering, Design & Selection 22:159-168, 2009; see, e.g., Discussion). Edwards et al. (J Mol Biol 334: 103-118, 2003; see abstract) also teach that over 1,000 different antibodies to a single Blys protein can be generated, all with different sequences, and representative of almost the entire extensive heavy and light chain germline repertoire, in addition to extensive diversity in the hCDR3 region sequences. Given that hundreds of unique antibody structures may bind a single antigen, a single species, or small group of related species, cannot be representative of all the antibodies that bind to the same epitope or the larger genus of antibodies that bind to all of the epitopes sharing as little as a single amino acid residue encompassed by the claim. Given the large number of epitopes within the amino acid sequence of SEQ ID NO: 1 (which is 245 amino acids long) encompassed by the instant claims, and the unpredictability of the structure of large number of antibodies that could bind to those epitopes, the instant specification does not describe representative examples to support the full scope of the claims. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Applicant’s attention is also directed to the decision in Amgen Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The court discussed whether an antibody is adequately described by describing a newly characterized antigen. Specifically, the court referred to the decision in Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011). In that case, the patentee claimed a genus of antibodies containing a human variable region that has particularly desirable therapeutic properties: high affinity, neutralizing activity, and A2 specificity. Although the specification disclosed human TNF-α protein, the court ruled that the generic antibody claims at issue were invalid for lack of written description, despite the disclosure of the structures of more than one species of antibody encompassed in the genus. The fact pattern is similar in the instant case. Specifically, in the instant case, the structure of the anti-CD19 scFv is provided by the amino acid sequence of SEQ ID NO: 1, while specific structures for antibodies that bind a scFv consisting of the amino acid sequence of SEQ ID NO: 1, bind the same epitope of the scFv as antibody 29E4B5, and compete against antibody 29E4B5 for binding to the scFv. are not. As in the court case, the instant claims recite a genus of antibodies that have a desirable property, i.e., binding an anti-CD19 scFv consisting of the amino acid sequence of SEQ ID NO: 1, binding the same epitope of the scFv as antibody 29E4B5, and competing against antibody 29E4B5 for binding to the scFv. Following the finding in Centocor, the instant claims are found to lack adequate written description.
The court in Amgen v. Sanofi further compares the requirements of enablement and written description, stating that:
“We cannot say that this particular context, involving a “newly characterized antigen” and 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. For us to draw such a conclusion, and transform a factual issue into a legally required inference, we would have to declare a contested scientific proposition to be so settled as to be entitled to judicial notice. That we cannot do.”
The court indicated that it has been hotly disputed whether or not knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. Citing Centocor again, the court provides an analogy for the antibody-antigen relationship as not quite a lock and key relationship but rather providing a lock and then searching for a key on a ring with a million keys on it. The court concludes that the “newly characterized antigen” test flouts basic legal principles of the written description requirement, reasoning that section 112 requires a written description of the invention, whereas the newly characterized antigen test allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen. The court urges that such constricts the “quid pro quo” of the patent system where one describes an invention in order to obtain a patent.
Accordingly, since the instant fact pattern fits the “newly characterized antigen” scenario, wherein the specification describes the structure of the target/antigen but not the structure of the genus of antibodies, the claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. Only an isolated antibody that binds anti-CD19 scFv and comprises (i) the six CDR amino acid sequences of SEQ ID NOs: 10-13 and 15-17 (for example) or (ii) the heavy chain variable domain (VH) amino acid sequence of SEQ ID NO: 2 or 20 and the light chain variable domain (VL) amino acid sequence of SEQ ID NO: 3 or 21, but not the full breadth of claims, meets the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). See also Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
3. Claims 1, 2, 5-18, 23, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hauskins et al. (WO 2018/023100; cited on the IDS of 01 November 2022).
Hauskins et al. teach anti-idiotype antibodies that specifically recognize anti-CD19 antibody moieties (page 1, [0003]). Hauskins et al. disclose that the anti-idiotype antibody targets anti-CD19 FMC63 (page 50, [0184]; page 60, [0224]). Hauskins et al. indicate that the anti-idiotype antibody is generated against the FMC63 immunogen sequence of SEQ ID NO: 34 (page 78, [0293]). It is noted that the amino acid sequence of SEQ ID NO: 34 of Hauskins et al. is 100% identical to the amino acid sequence of SEQ ID NO: 1 of the instant application (see sequence alignment below).
Qy=Instant SEQ ID NO: 1
Db=SEQ ID NO: 34 of Hauskins et al.
RESULT 1
AASEQ2_09272025_025024
Query Match 100.0%; Score 1289; DB 1; Length 245;
Best Local Similarity 100.0%;
Matches 245; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPS 60
Qy 61 RFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGE 120
Qy 121 GSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSE 180
Qy 181 TTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTS 240
Qy 241 VTVSS 245
|||||
Db 241 VTVSS 245
Thus, since the anti-idiotype antibody of Hauskins et al. is generated against the same amino acid sequence as the antibody of the instant claims, the anti-idiotype antibody of Hauskins et al. binds the same epitope and competes with the antibody of claim 1 of the instant application, absent evidence to the contrary ((In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977); In re Crish 292 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004)).
Hauskins et al. teach that the anti-idiotype antibody specifically binds to an anti-CD19 chimeric antigen receptor containing an antigen-binding portion derived from antibody FMC63, and that such CARs are expressed on a cell, meeting the limitations of instant claims 2 and 13 (page 79, [0275]).
Hauskins et al. disclose that the anti-idiotype antibody is an antigen-binding fragment, Fab fragment, F(ab’)2 fragment, Fab’ fragment, Fv fragment, and scFv, meeting the limitations of instant claim 5 (page 9, [0037]; page 32, [0121]).
Hauskins et al. teach nucleic acids encoding the anti-idiotype antibodies, a vector comprising the nucleic acids, host cells (such as mammalian cells) comprising the vector, and methods of producing the antibodies, meeting the limitations of instant claims 6-10, 23, and 24 (page 63, [0232] through page 65, [0240]).
Hauskins et al. disclose a method of measuring or detecting a target antibody, such as a CAR or cell expressing a CAR (page 118, [0142]). Hauskins et al. indicate that the anti-idiotype antibody binds, detects, identifies, and/or quantifies the CAR and/or cells expressing the CAR, meeting the limitations of instant claim 11 (page 118, [0142]; page 121, [0418]). Hauskins et al. teach that the target antibody (an anti-CD19 antibody) is contained in a CAR, wherein the CAR is expressed on the surface of a T cell, meeting the limitations of instant claims 13 and 14 (page 121, [0419]). Hauskins et al. disclose that the methods include incubating, treating, and/or contacting a sample and/or composition containing or suspected of containing the target anti-CD19 antibody with the anti-idiotype antibodies, meeting the limitations of claim 11 (page 119, [0414]; page 118, [0142]; pages 121-122, [0420-0421]; page 123, [0423]). The incubating or contacting is under conditions that allow for the formation of a complex between the anti-idiotype antibody and the target antibody (i.e., CAR) (page 118, [0142]; page 119, [0414]; pages 121-122, [0421]). Hauskins et al. indicate that the anti-idiotype antibody is conjugated to a detectable label, meeting the limitations of instant claim 12 (page 120, [0416]; page 123, [0423]). Hauskins et al. indicate that the sample is a biological sample, such as serum or blood sample, meeting the limitations of instant claim 18 (pages 119-120, [0415]). Hauskins et al. teach that anti-CD19 CAR T cells in the sample may be from a subject genetically engineered to express the anti-CD19 CAR, meeting the limitations of instant claims 14-18 (page 125, [0428] through page 128, [0433]; page 207, [0590]; page 208, [0595]).
4. Claims 1, 2, 5-19, 23, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wiltzius et al. (US 2018/0086846).
Wiltzius et al. teach an isolated antigen binding molecule, such as an antibody, that binds an anti-CD19 scFv molecule comprising the amino acid sequence of SEQ ID NO: 1 (page 1, [0007-0008]). It is noted that the amino acid sequence of SEQ ID NO: 1 of Wiltzius et al. is 100% identical to the amino acid sequence of SEQ ID NO: 1 of the instant application (see sequence alignment below).
Qy=instant SEQ ID NO: 1
Db=SEQ ID NO: 1 of Wiltzius et al.
US-15-717-691-1
Sequence 1, US/15717691
Publication No. US20180086846A1
GENERAL INFORMATION
APPLICANT: KITE PHARMA, INC.
TITLE OF INVENTION: ANTIGEN BINDING MOLECULES AND METHODS OF USE THEREOF
FILE REFERENCE: K-1036.02
CURRENT APPLICATION NUMBER: US/15/717,691
CURRENT FILING DATE: 2017-09-27
PRIOR APPLICATION NUMBER: 62/401,007
PRIOR FILING DATE: 2016-09-28
NUMBER OF SEQ ID NOS: 82
SEQ ID NO 1
LENGTH: 267
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide
Query Match 100.0%; Score 1289; Length 267;
Best Local Similarity 100.0%;
Matches 245; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 23 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPS 82
Qy 61 RFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 83 RFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGSTSGSGKPGSGE 142
Qy 121 GSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 143 GSTKGEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSE 202
Qy 181 TTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 203 TTYYNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTS 262
Qy 241 VTVSS 245
|||||
Db 263 VTVSS 267
Thus, since the antigen binding molecule of Wiltzius et al. is generated against the same amino acid sequence as the antibody of the instant claims, the antigen binding molecule of Wiltzius et al. binds the same epitope and/or competes with the antibody of claim 1 of the instant application, absent evidence to the contrary ((In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977); In re Crish 292 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004)).
Wiltzius et al. teach that the antigen binding molecule binds a molecule comprising SEQ ID NO: 1, and that the molecule comprising SEQ ID NO: 1 is expressed on the surface of a cell, meeting the limitations of instant claim 2 (page 8, [0035-0036]; page 9, [0039]; page 47, [0380]).
Wiltzius et al. disclose that the antigen binding molecule includes fragments, such as Fabs, F(ab’)2, and scFvs, meeting the limitations of instant claim 5 (page 1, [0008]; page 13, [0085]; page 18, [0136]).
Wiltzius et al. teach a polynucleotide encoding the heavy and light chains of the antigen binding molecule, meeting the limitations of instant claim 6 (pages 2-3, [0018]). Wiltzius et al. also disclose a vector comprising the polynucleotides, a host cell (such as a mammalian cell) comprising the vector, and a method of making the antigen binding molecule, meeting the limitations of instant claims 7-10, 23, and 24 (pages 2-3, [0018]; page 11, [0066-0067]; page 29, [0147-0148, 0150]; pages 40-41, [0315-0319]).
Wiltzius et al. disclose a method of determining a number of immune cells (such as T cells) presenting a molecule comprising the anti-CD19 scFv molecule amino acid sequence of SEQ ID NO: 1 in a sample, wherein the method comprises (a) providing a sample comprising cells known or suspected to be presenting a molecule comprising SEQ ID NO: 1; (b) contacting the same of (a) with an antigen binding molecule that specifically binds the molecule comprising SEQ ID NO: 1, the antigen binding molecule further comprising a detectable label, under conditions that permit the formation of a binding complex; and (c) determining the number of cells present in a binding complex of (b) in the sample, meeting the limitations of instant claims 11-13 (page 4-5, [0024]; pages 43-44, [0346-0351]; page 7, [0031-0032]; page 47, [0380]).
Wiltzius et al. indicate that the molecule comprising the anti-CD19 scFc of SEQ ID NO: 1 in the method is a CAR, meeting the limitations of instant claim 13 (page 7, [0032]; (page 8, [0035]; page 9, [0039]; page 44, [0350]).
Wiltzius et al. teach that the T cells in the method can be obtained from a subject, blood, extracted tissue, cell culture media, tissue grown ex vivo, etc., meeting the limitations of instant claims 14-18 (page 5, [0024]; page 41, [0323]; page 44, [0349]). Wiltzius et al. indicate that the subject may be a human cancer patient, meeting the limitations of instant claim 19 (page 17, [0119]; page 42, [0330]).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
5. Claims 1, 2, and 5-24 are rejected under 35 U.S.C. 103 as being unpatentable over Wiltzius et al. (US 2018/0086846) and Qasim et al. (Sci Translat Med 9: eaaj2013, 2017).
The teachings of Wiltzius et al. are set forth directly above.
Wiltzius et al. do not teach determining a number of immune cells (such as T cells) presenting a molecule comprising the anti-CD19 scFv molecule comprising the amino acid sequence of SEQ ID NO: 1 in a sample, wherein the sample is a biological sample obtained from a human cancer subject with a relapsed/refractory B-cell malignancy. Wiltzius et al. also do not teach that the T cells measured in the method comprise a disrupted TRAC gene.
Qasim et al. teach that autologous T cells engineered to express chimeric antigen receptors (CARs) against leukemic antigens, such as CD19 on B cells, can be highly efficacious in refractory relapsed leukemia (page 1, column 1, 2nd full paragraph). However, in heavily treated cancer patients, it is not always possible to manufacture an effective therapeutic product (page 1, column 1, 2nd full paragraph). Alternative approaches to using off-the-shelf therapies derived from non-matched donors are attractive, but must overcome critical HLA barriers (page 1, column 1, 2nd full paragraph; page 4). Qasim et al. disclose that HLA-disparate T cells must evade host-mediated immunity and deliver antileukemic effects without graft-versus-host disease (GVHD) (page 1, column 1, 2nd full paragraph). To reduce the risk of GVHD for patients, Qasim et al. teach the generation of universal CAR19 (UCART19) T cells by the transcription of activator-like effector nuclease (TALEN)-mediated gene editing of T cell receptor α chain (TRAC) and CD52 gene loci, meeting the limitations of instant claim 22 (abstract; page 1, column 2, 1st full paragraph). Qasim et al. teach that administration of the UCART19 T cells to infants with relapsed refractory CD19+ B cell acute lymphoblastic leukemia achieved remission within 28 days, meeting the limitations of instant claims 20 and 21 (abstract; Figures 2-3).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to modify the method of determining a number of immune cells (such as T cells) presenting a molecule comprising the anti-CD19 scFv molecule in a sample from a patient as taught by Wiltzius et al. by obtaining the sample from a human subject with a relapsed/refractory B-cell malignancy, wherein the subject has been administered CD19 CAR T cells with a disrupted TRAC gene, as taught by Qasim et al. The person of ordinary skill in the art would have been motivated to make those modifications to monitor cell number and assess the therapeutic efficacy of CD19 CAR T cells with a disrupted TRAC gene administered to patients with a refractory B-cell malignancy (Wiltzius et al., page 18, [0128] page 43, [0346]). It is also noted that the skilled artisan would have been motivated to disrupt the TRAC gene in the administered and quantified CD19 CAR T cells to reduce the risk of GVHD in patients administered the cells (see Qasim et al. abstract; page 1, column 2, 1st full paragraph). The person of ordinary skill in the art reasonably would have expected success because the anti-idiotype antigen binding molecule of Wiltzius et al. successfully recognizes and isolates cells expressing anti-CD19 (pages 61-62, Examples 1-2). Additionally, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007)). Therefore, the claimed invention as a whole was clearly prima facie obvious over the prior art.
Conclusion
No claims are allowable.
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BEB
Art Unit 1647
26 September 2025
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647