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 .
1. Claims 1-18, 20, and 22 are pending and being examined.
Claim Objections
2. Claim 18 is free of the art but is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
3. Claims 3 and 4 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.
Claim 3 recites the limitation "the heavy chain of the Fab fragment". There is insufficient antecedent basis for this limitation in the claim.
Claim 4 recites the limitation "the heavy chain". There is insufficient antecedent basis for this limitation in the claim.
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.
4. Claims 1-17, 20, and 22 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 pre-AIA 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 antibody, comprising an anti-signal regulatory protein alpha (SIRPα) unit and an anti-programmed death-ligand 1 (PD-L1) unit, wherein the anti-SIRPα unit comprises a Fab fragment having binding specificity to a human SIRPα protein, and the anti-PD-L1 unit comprises a single-domain antibody (sdAb) having binding specificity to a human PD-L1 protein. Claim 20 further requires the antibody to function in treating cancer. The claims are drawn to a vast genus of antibodies identified by function only, where the function is to have binding specificity to a human SIRPα protein, have binding specificity to a human PD-L1 protein, and to treat cancer. No antibody structure is recited.
Dependent claims 5-13 recite sequences of the anti-SIRPα unit critical to SIRPα binding but do not recite the sdAb sequence critical to the function of binding PD-L1.
Dependent claims 14-17 recite sequences of the anti-PD-L1 sdAb critical to binding PD-L1 but do not recite the Fab sequences critical to binding SIRPα.
The instant specification discloses seven structurally distinct anti-SIRPα antibodies and their VH and VL sequences comprising defined CDR sequences (Table 1), and humanized variable domains comprising the CDR sequences (Tables 2A-8D). The instant specification also discloses the three CDR sequences of 50 structurally distinct sdAbs that bind to PD-L1 (Table 24) and the their full VH domain sequence (Table 27). Table 30 discloses the anti-PD-L1 sdAb and anti-SIRPα light and heavy chain sequences used to construct each bispecific antibody.
Thus, the instant specification describes the sequences of seven structurally distinct anti-SIRPα antibodies and 50 structurally distinct anti-PD-L1 sdAbs that function to bind SIRPα and PD-L1 as claimed. Other than for these disclosed antibody sequences, the specification fails to disclose the structural sequence required of any other anti-SIRPα antibody to possess the function of binding SIRPα and an anti-PD-L1 sdAb to possess the function of binding PD-L1, and a bispecific antibody treating cancer.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative Fab-containing antibodies that function to bind SIRPα and representative single domain antibodies that function to bind, 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 bind SIRPα and PD-L1 and 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. The SIRPα and PD-L1 antigens provide no information about the structure of an antibody that binds to them and treats cancer.
In this case, the only factor present in the claims is a recitation of the antibody function. The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification discloses only seven exemplary structurally distinct anti-SIRPα antibody sequences and 50 exemplary structurally distinct anti-PD-L1 sdAb sequences that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. Other than for the disclosed antibody sequences, the specification fails to provide the structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of antibody sequences for the vast genus of antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to perform the claimed method.
The claims broadly encompass an antibody comprising any anti-SIRPα antibody Fab fragment and/or any anti-PD-L1 sdAb that functions as claimed. Applicants have not established any reasonable structure-function correlation with regards to the sequences in the variable domains or CDRs that can be altered and still maintain SIRPα and PD-L1 binding function and or treat cancer. The instant claims attempt to claim every antibody comprising an anti-SIRPα Fab fragment and/or anti-PD-L1 sdAb that would achieve a desired result, i.e., bind SIRPα, bind PD-L1, and treat cancer, wherein the instant specification does not describe representative examples to support the full scope of the claims because the instant specification discloses seven structurally distinct anti-SIRPα Fab fragments and 50 structurally distinct anti-PD-L1 sdAbs. Given the well-known high level of polymorphism of antibody CDR sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of antibodies encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of seven structurally distinct anti-SIRPα antibodies to the structure of any and all anti-SIRPα anitbodies, or extrapolate the structure of 50 structurally distinct anti-PD-L1 sdAbs to the structure of any and all anti-PD-L1 sdAbs, as broadly claimed and required to practice the claimed method. Therefore, one could not readily envision members of the broadly claimed genus.
Given the lack of representative examples to support the full scope of the claimed antibodies used in the claimed method, and lack of reasonable structure-function correlation with regards to the unknown sequences in the variable domains or CDRs that provide SIRPα- and PD-L1-binding function and cancer treating function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibodies comprising a Fab fragment that binds SIRPα, a sdAB that binds PD-L1, or treat cancer 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 Suggestion: Amend claim 1 to recite at minimum, the six heavy and light chain CDR sequences critical to the anti-SIRPα Fab fragment binding function and the three CDR sequences critical to the anti-PD-L1 sdAb binding function.
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. Claim(s) 1-4, 14-17, 20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/233539, Yin et al, filed May 2020, claiming priority to May 2019; in view of WO 2020/102422, Puro et al, filed November 2019, published May 2020.
Yin teaches a bispecific antibody comprising:
(i) an anti-CD47 antibody comprising a Fab fragment; and
(ii) an anti-PD-L1 single domain antibody (sdAb);
wherein the bispecific antibody comprises an Fc fragment and the anti-CD47 antibody is full length (claims 1-5, 9, 19; [130]; [146-147]);
wherein the anti-PD-L1 antibody is fused to the C-terminus of the heavy chain of the anti-CD47 antibody (claims 1-5, 9, 19; [130]);
wherein the PD-L1 sdAb comprises SEQ ID NO:14 that is 100% identical to instant SEQ ID NO:513 comprising instant CDR SEQ ID NOs:213, 313, and 413 (see sequence alignment below);
wherein the bispecific antibody comprising PD-L1 sdAb SEQ ID NO:14 comprises the complete heavy chain Fab fusion of SEQ ID NO:48 that is identical to amino acids 104-580 of instant SEQ ID NO:559 and comprises a different N-terminal variable region/CDR sequences for the anti-CD47 antibody binding regions (claim 19; [130]) (see sequence alignment below). In other words, Yin teaches an anti-CD47 antibody with the C-terminus of the heavy chain fused to the same anti-PD-L1 sdAb SEQ ID NO:513 instantly claimed, and comprises the same heavy chain constant region and linker as instant SEQ ID NO:559 - the only difference being the anti-CD47 Fab fragment sequences are present instead of anti-SIRPα sequences, as required by the instant claims.
Yin further teaches a method of treating CD47 and/or PD-L1 expressing cancer in a patient comprising administering to the patient the bispecific antibody, wherein the cancer is colon, breast, lung, ovarian cancer or a hematological cancer including leukemia and lymphoma (claims 24-39; [213-221]).
Yin further teaches the anti-CD47 antibody functions to inhibit binding of SIRPα to CD47 ([139]). CD47 is a ubiquitous innate immune checkpoint receptor that serves as a "don't eat me" signal. It binds to its receptor SIRPα that is primarily expressed on phagocytic macrophages and dendritic cells, and, therefore, leads to inhibition of phagocytosis. Cancer cells have evolved to evade immune surveillance by upregulating CD47 expression to prevent phagocytosis. CD47 is broadly overexpressed on hematological and solid tumors, which highly correlates with poorer prognosis. Thus, blocking the CD47-SIRPα interaction with anti-CD47 antibodies or high-affinity SIRPα variant has become a potential strategy to promote macrophage-dependent destruction of tumors ([09]). As both CD47 and PD-L1 are overexpressed on some tumor cells, particularly, co-expression of these two proteins was identified in melanoma patients, it is reasonable to maximize cancer treatment by simultaneously blocking CD47 and PD-L1. Yin teaches the prior art demonstrated synergistic activity could be achieved after a combinatorial blockade of PD-L1 and CD47 ([10]).
Yin does not teach substituting the anti-CD47 antibody portion with an anti-SIRPα antibody in the bispecific antibody.
Puro teaches a bispecific antibody binding to SIRPα and PD-L1 that functions to inhibit binding of SIRPα with CD47, treat cancer, and increase phagocytosis of tumor cells, wherein the cancer is colon, breast, lung, ovarian, leukemia or lymphoma (claims 1, 8-23 and 26; [162-163]). Puro teaches the sequences of SIRPPα antibodies that block CD47/SIRPα binding (claim 1; Example 1 and 6). Puro demonstrates that combined SIRPα antibodies and anti-PD-L1 antibodies induced increased phagocytosis of tumor cells by macrophages compared to either antibody alone (Example 11; Figure 10). Puro also demonstrates that combined therapy of SIRPα antibodies and anti-CD47 antibodies induced increased phagocytosis of tumor cells by macrophages compared to either antibody alone (Example 9). Puro explains:
[0004] An important corollary of the action of CD47 as a“don't eat me” signal is its role as a“marker of self’. This provides a significant hindrance to phagocytosis of self and blocks a subsequent autoimmune response (Oldenborg, 2002, Oldenborg 2004). Cancer cells use CD47 to mask themselves in “selfness” consequently evading both the innate and adaptive immune systems. Blocking the interaction SIRPa on innate immune cells such as macrophages and dendritic cells with CD47 on tumor cells has emerged as a viable target in cancer therapy. Preclinical data has indicated that, similar to anti-CD47 antibodies, anti-SIRPa antibodies that block the SIRPa/CD47 interaction exhibit anti-tumor efficacy in mouse tumor models, either as monotherapy or in combination with other agents (Gauttier, 2017; Ring, 2017; Yanigita, 2017; Poirier, 2018; and Guattier, 2018). Importantly, generation of an adaptive immune response, in addition to the innate immune response following interruption of the SIRPa/CD47 interaction, appears to be critical to obtaining a robust anti-tumor response (Tseng 2013, Li 2015, Xu 2017).
[0005] Expression of SIRPa on DC cells and its interaction with CD47 on T-cells appears to be important in inducing the adaptive immune response. Blockade of the SIRPa/CD47 interaction was reported to affect the DCs ability to stimulate the antigen- specific CD8+ T-cell response and this was correlated with an enhanced DC-mediated response to tumor DNA (Liu 2015, Xu 2017).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to substitute the SIRPα antibody of Puro for the CD47 antibody in the bispecific antibody of Yin. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Yin and Puro both teach the known function of anti-CD47 and anti-SIRPα antibodies is equivalent, where they both inhibit binding of SIRPα with CD47, enhance phagocytosis of tumor cells, and treat cancer; (2) Puro suggests combining anti-SRPα antibody with anti-PD-L1 antibody as a bispecific antibody and demonstrates that the combination of SIRPα antibodies and anti-PD-L1 antibodies induced increased phagocytosis of tumor cells by macrophages compared to either antibody alone; and (3) Puro teaches the known sequences of anti-SIRPα antibodies for construction for bispecific antibodies.
Instant specification Table 30 SEQ ID NO:559 (PD-L1/SIRPa fusion heavy chain):
N-terminal SIRPα variable region underlined and C-terminal PD-L1 sdAb underlined.
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Instant SEQ ID NO:559 “PD-L1/SIRPa-HC1 heavy chain” aligned with Yin SEQ ID NO:48 (PD-L1/CD47-HC1 heavy chain):
RESULT 3
BIQ86871
ID BIQ86871 standard; protein; 583 AA.
XX
AC BIQ86871;
XX
DT 21-JAN-2021 (first entry)
XX
DE Anti-CD47 antibody heavy chain-anti-PD-L1 sdAb fusion, SEQ ID 48.
XX
KW CD47; Cluster of differentiation 47; PD-L1 protein;
KW Programmed cell death ligand 1; Programmed death-ligand 1;
KW antibody therapy; antimicrobial-gen.; cancer; cytostatic; fusion protein;
KW heavy chain; infectious disease; monoclonal antibody;
KW prophylactic to disease; single domain antibody; therapeutic.
XX
OS Unidentified.
OS Synthetic.
XX
CC PN WO2020233539-A1.
XX
CC PD 26-NOV-2020.
XX
CC PF 18-MAY-2020; 2020WO-CN090753.
XX
PR 17-MAY-2019; 2019WO-CN087364.
XX
CC PA (NANJ-) NANJING GENSCRIPT BIOTECH CO LTD.
XX
CC PI Yin L, Li Z, Zhou T, Fang Z;
XX
DR WPI; 2020-B7128N/099.
DR N-PSDB; BIQ86870.
XX
CC PT New isolated anti-cluster of differentiation 47/anti-programmed death-
CC PT ligand 1 multiple antigen binding protein or its antigen binding useful
CC PT in pharmaceutical composition for treating human having or at risk of
CC PT having cancer.
XX
CC PS Claim 19; SEQ ID NO 48; 97pp; English.
XX
CC The present invention relates to a novel isolated multiple antigen
CC binding protein comprising a first antigen binding portion and a second
CC antigen portion. The first antigen binding portion comprises a heavy
CC chain region of SEQ ID NO: 4 (see BIQ86827) and a light chain region of
CC SEQ ID NO: 6 (see BIQ86829) which specifically binds to a cluster of
CC differentiation 47 (CD47) and the second antigen binding portion
CC comprises a single-domain antibody (sdAb) selected from SEQ ID NO: 14
CC (see BIQ86837), SEQ ID NO: 16 (see BIQ86839) and SEQ ID NO: 18 (see
CC BIQ86841) that specifically binds to a programmed death-ligand 1 (PD-L1).
CC The The invention further claims: (1) an isolated nucleic acid encoding
CC the anti-CD47/anti-PD-L1 multiple antigen binding protein; (2) an
CC isolated vector comprising the nucleic acid; (3) a host cell comprising
CC the isolated vector; (4) a pharmaceutical composition comprising the anti
CC -CD47/anti-PD-L1 multiple antigen binding protein and a carrier; and (5)
CC a method for treating a subject having or at risk of having a CD47 and/or
CC PD-L1-related disease. The anti-CD47/anti-PD-L1 multiple antigen binding
CC protein of the present invention is used for preparing a pharmaceutical
CC composition for preventing and treating a CD47 and/or PD-L1-related
CC disease such as cancer and pathogenic infection.
XX
SQ Sequence 583 AA;
Query Match 94.8%; Score 2924.5; Length 583;
Best Local Similarity 94.9%;
Matches 553; Conservative 13; Mismatches 14; Indels 3; Gaps 2;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGFNFEDTYMHWVRQAPGQGLEWMGRIDPADADTKY 60
:||||||||||||||:||||||||||::| ::||||||||||||||| || :|::|:
Db 1 EVQLVQSGAEVKKPGSSVKVSCKASGYSFTHHWIHWVRQAPGQGLEWMGMIDASDSETRL 60
Qy 61 NPKFQDRVTITVDTSTNTAYMELSSLRSEDTAVYYCVR-GNYV--NWGQGTTVTVSSAST117
: ||:|||||| | ||:||||||||||||||||||| | | | ||||||||||||||
Db 61 SQKFKDRVTITADKSTSTAYMELSSLRSEDTAVYYCARLGRYYFDYWGQGTTVTVSSAST120
Qy 118 KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY177
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 KGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLY180
Qy 178 SLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLF237
||||||||||||||||||||||||||||||||||||||||||||||||||| ||||||||
Db 181 SLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLF240
Qy 238 PPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV297
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVV300
Qy 298 SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV357
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQV360
Qy 358 SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVF417
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 SLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVF420
Qy 418 SCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLS477
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 SCSVMHEALHNHYTQKSLSLSLGKGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLS480
Qy 478 CAASGRTFVTYGMGWFRQAPGKGREFVSAISWSGSMTSYGDSVKGRFTISRDNAKNTLYL537
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CAASGRTFVTYGMGWFRQAPGKGREFVSAISWSGSMTSYGDSVKGRFTISRDNAKNTLYL540
Qy 538 QMNSLRPEDTAVYYCAAALGAVVYTTREPYTYWGQGTLVTVSS 580
|||||||||||||||||||||||||||||||||||||||||||
Db 541 QMNSLRPEDTAVYYCAAALGAVVYTTREPYTYWGQGTLVTVSS 583
Instant SEQ ID NO:513 PD-L1 sdAb aligned with Yin SEQ ID NO:14:
ID BIQ86837 standard; protein; 124 AA.
XX
AC BIQ86837;
XX
DT 21-JAN-2021 (first entry)
XX
DE Anti-PD-L1 single domain antibody heavy chain variable region, SEQ ID 14.
XX
KW PD-L1 protein; Programmed cell death ligand 1; Programmed death-ligand 1;
KW antibody therapy; antimicrobial-gen.; cancer; cytostatic;
KW heavy chain variable region; infectious disease; prophylactic to disease;
KW single domain antibody; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2020233539-A1.
XX
CC PD 26-NOV-2020.
XX
CC PF 18-MAY-2020; 2020WO-CN090753.
XX
PR 17-MAY-2019; 2019WO-CN087364.
XX
CC PA (NANJ-) NANJING GENSCRIPT BIOTECH CO LTD.
XX
CC PI Yin L, Li Z, Zhou T, Fang Z;
XX
DR WPI; 2020-B7128N/099.
DR N-PSDB; BIQ86836.
XX
CC PT New isolated anti-cluster of differentiation 47/anti-programmed death-
CC PT ligand 1 multiple antigen binding protein or its antigen binding useful
CC PT in pharmaceutical composition for treating human having or at risk of
CC PT having cancer.
XX
CC PS Claim 12; SEQ ID NO 14; 97pp; English.
XX
CC The present invention relates to a novel isolated multiple antigen
CC binding protein comprising a first antigen binding portion and a second
CC antigen portion. The first antigen binding portion comprises a heavy
CC chain region of SEQ ID NO: 4 (see BIQ86827) and a light chain region of
CC SEQ ID NO: 6 (see BIQ86829) which specifically binds to a cluster of
CC differentiation 47 (CD47) and the second antigen binding portion
CC comprises a single-domain antibody (sdAb) selected from SEQ ID NO: 14
CC (see BIQ86837), SEQ ID NO: 16 (see BIQ86839) and SEQ ID NO: 18 (see
CC BIQ86841) that specifically binds to a programmed death-ligand 1 (PD-L1).
CC The The invention further claims: (1) an isolated nucleic acid encoding
CC the anti-CD47/anti-PD-L1 multiple antigen binding protein; (2) an
CC isolated vector comprising the nucleic acid; (3) a host cell comprising
CC the isolated vector; (4) a pharmaceutical composition comprising the anti
CC -CD47/anti-PD-L1 multiple antigen binding protein and a carrier; and (5)
CC a method for treating a subject having or at risk of having a CD47 and/or
CC PD-L1-related disease. The anti-CD47/anti-PD-L1 multiple antigen binding
CC protein of the present invention is used for preparing a pharmaceutical
CC composition for preventing and treating a CD47 and/or PD-L1-related
CC disease such as cancer and pathogenic infection.
XX
SQ Sequence 124 AA;
ALIGNMENT:
Query Match 100.0%; Score 650; Length 124;
Best Local Similarity 100.0%;
Matches 124; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGRTFVTYGMGWFRQAPGKGREFVSAISWSGSMTSY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGRTFVTYGMGWFRQAPGKGREFVSAISWSGSMTSY 60
Qy 61 GDSVKGRFTISRDNAKNTLYLQMNSLRPEDTAVYYCAAALGAVVYTTREPYTYWGQGTLV120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GDSVKGRFTISRDNAKNTLYLQMNSLRPEDTAVYYCAAALGAVVYTTREPYTYWGQGTLV120
Qy 121 TVSS 124
||||
Db 121 TVSS 124
6. Claim(s) 5-13 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/233539, Yin et al, filed May 2020, claiming priority to May 2019 and WO 2020/102422, Puro et al, filed November 2019, published May 2020 as applied to claims 1-4, 14-17, 20, and 22 above, and further in view of WO 2021/129697, Li, claiming priority to December 24, 2019.
The applied reference WO 2021/129697 has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Yin and Puro (the combined references) teach a bispecific antibody binding to SIRPα and PD-L1, wherein the SIRPα antibody comprises a Fab fragment and the PD-L1 antibody is a sdAb, as set forth above.
The combined references do not teach utilizing anti-SIRPα antibody heavy and light chain variable domain sequences of instant SEQ ID NOs:1, 2, 23-29, 3, 4, 39-46, 5, 6, and 55-62.
Li teaches anti-SIRPα antibodies comprising the same variable heavy and light chain sequences as instant SEQ ID NOs: 1, 2, 23-29, 3, 4, 39-46, 5, 6, and 55-62 (claims 1-9; [6-18]; [64-98]; Tables 1, 2A-8D). Li teaches the anti-SIRPα antibodies function to block the interaction of SIRPα and CD47, induce macrophage-mediated phagocytosis of tumor cells expressing CD47, and treat cancer including colon, breast, lung, ovarian, leukemia or lymphoma (abstract; claims 19-21; [116-122]; Example 4). Li demonstrates that anti-SIRPα antibodies combined with anti-PD-L1 antibody successfully induced macrophage mediated phagocytosis of CD47/PD-L1-expressing tumor cells in vitro and exhibited the highest phagocytosis compared to either agent alone (Example 4; Figure 4). Li suggests the anti-SIRPα antibodies can be bispecific and target another tumor antigen including PD-L1 ([110-111]), wherein the bispecific antibody can comprise antibody formats including a Fab fragment and sdAb ([112]).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to substitute the SIRPα antibody of Li for the SIRPα antibody in the bispecific antibody of the combined references. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Puro and Li teach the known function of the anti-SIRPα antibodies is equivalent, where they inhibit binding of SIRPα with CD47, enhance phagocytosis of tumor cells, and treat cancer; (2) Li suggests making the anti-SIRPα antibody bispecific to target a second tumor antigen including PD-L1, suggests the bispecific antibody comprise a Fab fragment and sdAb, and demonstrates that the combination of SIRPα antibodies and anti-PD-L1 antibodies induced increased phagocytosis of tumor cells by macrophages compared to either antibody alone; and (3) Li teaches the known sequences of anti-SIRPα antibodies for construction for bispecific antibodies.
7. Conclusion: Claims 1-17, 20, and 22 are rejected. Claim 18 is objected to.
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/Laura B Goddard/Primary Examiner, Art Unit 1642