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 .
DETAILED ACTION
Claims 1-6, 10-13, 15-18, 21, 25, 27, 29, 31, 33-34, 43-45 and 54-58 are pending and currently under prosecution
Claim Rejections - 35 USC § 112
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.
Claims 1-6, 10-13, 15-18, 21, 25, 27, 29, 31, 33-34, 43-45 and 54-58 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.
Claims 1 and 3 are indefinite in the use of the parenthesis in the claims, in that it is not clear whether this recitation is intended to be part of the claim or not.
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.
Claims 1-6, 10-13, 15-18, 21, 25, 27, 29, 31, 33-34, 43-45 and 54-58 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. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to an isolated antibody that binds human PD-L1 comprising an immunoglobulin heavy chain variable region comprising the instantly claimed sequences, and/or an immunoglobulin light chain variable region comprising the instantly claimed sequences. Thus, the claims recite a partial structure of the anti-PD-L1 antibody as it recites that the antibody may comprise either a heavy chain variable region or a light chain variable region.
The instant specification does not recite any examples of the instantly claimed antibody comprising either a heavy chain variable region only or a light chain variable region only.
By the time of the filing of the instant application, it was well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three “complementarity determining regions” (“CDRs”) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro & Fransson, Frontiers in Bioscience 2008; 13:1619-33; (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). Humanized antibodies comprise only the CDRs, or in some cases an abbreviated subset of residues within the CDRs, of a parental rodent antibody in the context of human framework sequences. Id. at Section 4. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody. Id. at Section 4.
Antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (Gershoni et al., Epitope Mapping, Biodrugs 2007; 21 (3): 145-156 page 146 section 1.1). The skilled artisan therefore understood that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence and length of VH-CDR3.
Further, it is not possible to predict the amino acid sequence when an epitope is recited, because there are many different epitope arrangements, such as linear and discontinuous epitopes that is dictated by the unique interaction between an antibody and its cognate epitope (Blythe et al., Benchmarking B cell epitope prediction: Underperformance of existing methods, Protein Science (2005), 14:246–248 pg. 246) . 3D structural analyses of antibody-epitope binding highlighting that the deficiency in the ability to predict the structural features of an antibody when the epitope is disclosed (Schreiber et al.,3D-Epitope-Explorer (3DEX): Localization of Conformational Epitopes within Three-Dimensional Structures of Proteins, Wiley Interscience, 2005 42–44, 60596, page 879).
To provide adequate written description and evidence of possession of the claimed composition antibody genus, the instant specification can structurally describe representative antibodies, that function to bind human PD-L1 and treating functions as claimed, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
Although Applicants may argue that it is possible to screen for antibodies that function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed.
Given the lack of representative examples to support the full scope of the claimed antibodies, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibodies that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Examiner’s suggestion: Amend claim 1 to recite “and” an immunoglobulin light chain variable region.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 4, 5, 6, 10, 11, 12, 57 and 58 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Yoo et al (WO2016160792 A1; Published 10/6/2016).
Yoo et al teaches an isolated antibody tha binds to human-PD-L1 comprising a light chain variable region comprising a CDRL1-3 comprising the amino acid sequences that match 100% to the instantly claimed 179, 180, and 181. [see sequence alignment below] Yoo teaches that the antibody comprises a heavy chain and/or light chain constant region, wherein the heavy chain constant region is selected from IgG1, IgG2, IgG3, and IgG4. [0076] Yoo teaches that the antibody has a KD of 5 nM or lower. [0073] Yoo teaches an isolated nucleic acid comprising a nucleotide sequences that encodes either the heavy chain or light variable regions. [0015] Yoo teaches an expression vector and a host cell comprising the expression vector of claim 11. [0087] Yoo teaches a pharmaceutical composition comprising the antibody. [0104] Lastly, Yoo teaches a method for treating cancer comprising administering the anti-PD-L1 antibody. [0156]
SEQUENCE ALIGNMENTS
SEQ ID NOS: 179-180-181
RESULT 1
BDG83233
(NOTE: this sequence has 2 duplicates in the database searched)
ID BDG83233 standard; protein; 111 AA.
XX
AC BDG83233;
XX
DT 01-DEC-2016 (first entry)
XX
DE Anti-glyc PD-L1 mAb STM004 kappa light chain variable region, SEQ ID 11.
XX
KW B7-H1 protein; CD274 protein; PD-L1 protein; PDD1L1 protein;
KW Programmed cell death ligand 1; antibody therapy; bladder cancer;
KW brain tumor; breast tumor; cancer; colon tumor; cytostatic;
KW esophagus tumor; head and neck tumor; hematological neoplasm;
KW immunoassay; light chain variable region; liver tumor; lung tumor;
KW monoclonal antibody; ovary tumor; pancreas tumor;
KW programmed death ligand-1 protein; prostate tumor; protein detection;
KW rectal tumor; screening; skin cancer; stomach tumor; testis tumor;
KW therapeutic; uterine cervix tumor; uterus tumor.
XX
OS Homo sapiens.
XX
CC PN WO2016160792-A1.
XX
CC PD 06-OCT-2016.
XX
CC PF 29-MAR-2016; 2016WO-US024691.
XX
PR 30-MAR-2015; 2015US-0140135P.
XX
CC PA (TEXA ) UNIV TEXAS SYSTEM.
CC PA (STCU-) STCUBE & CO INC.
XX
CC PI Chung EM, Hung M, Kim Y, Li C, Lim S, Yoo SS;
XX
DR WPI; 2016-62751Y/71.
DR N-PSDB; BDG83232.
XX
CC PT New antibody which selectively binds to glycosylated Programmed death-
CC PT ligand 1 (PD-L1), useful for treating a PD-L1 positive cancer and
CC PT assaying for the presence of glycosylated PD-L1 in a biological sample.
XX
CC PS Claim 17; SEQ ID NO 11; 136pp; English.
XX
CC The present invention relates to novel anti-glycosylated programmed death
CC -ligand 1 (PD-L1) antibodies and their use in treating a PD-L1 positive
CC cancer and for assaying the presence of glycosylated PD-L1 in a
CC biological sample. The invention also provides: isolated nucleic acid
CC molecules encoding the heavy chain variable (VH) region and light chain
CC variable (VL) region of anti-PD-L1 antibody; a method for treating a PD-
CC L1 positive cancer in a subject; a method for assaying the presence of
CC glycosylated PD-L1 in a biological sample; an isolated polypeptide
CC comprising a fragment of human PD-L1; a composition comprising the anti-
CC PD-L1 antibody; and a method for identifying a candidate cancer patient
CC for treatment with an agent that blocks the binding of PD-L1. The
CC antibody and composition are useful for treating a PD-L1 positive cancer;
CC and assaying for the presence of glycosylated PD-L1 in a biological
CC sample. The cancer is a breast cancer, lung cancer, head and neck cancer,
CC prostate cancer, esophageal cancer, tracheal cancer, skin cancer brain
CC cancer, liver cancer, bladder cancer, stomach cancer, pancreatic cancer,
CC ovarian cancer, uterine cancer, cervical cancer, testicular cancer, colon
CC cancer, rectal cancer, hematological cancer or skin cancer. The present
CC sequence is an anti-glyc PD-L1 mAb STM004 kappa light chain variable
CC region of the invention.
XX
SQ Sequence 111 AA;
Query Match 77.0%; Score 84.7; Length 111;
Best Local Similarity 29.3%;
Matches 22; Conservative 0; Mismatches 0; Indels 53; Gaps 2;
Qy 1 ESVEFYGTTL-----------------AAS------------------------------ 13
|||||||||| |||
Db 27 ESVEFYGTTLMQWYQQKPGQPPRLLIYAASNVESGVPARFSGSGSGTDFSLNIHPVEDDD 86
Qy 14 ------QQSRKVPYT 22
|||||||||
Db 87 IAMYFCQQSRKVPYT 101
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
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/SARAH A ALSOMAIRY/ Examiner, Art Unit 1646
/Zachariah Lucas/ Supervisory Patent Examiner, Art Unit 1600