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 the Claims
Claims 1 – 24 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application IL 286430, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. In particular, IL 286430 fails to support the sequences of SEQ ID NOs: 1 – 3 and 4 – 6 of present claim 6, the sequences of SEQ ID NOs: 11 – 13 and 14 – 16 of present claim 7, the sequences of SEQ ID NOs: 21 – 23 and 24 – 26 of present claim 8 and the sequences of SEQ ID NOs: 31 – 33 and 34 – 36 of present claim 9, the sequences of SEQ ID NOs: 7, 8, 17 and 18 of present claim 13, and the sequences of SEQ ID NOs: 27, 28, 37 and 38 of present claim 14.
Furthermore, neither PCT/IL2022/050995 nor the present specification discloses the sequences of SEQ ID NOs: 5, 15, 25 and 35 (see the rejection under 112(a) below).
However, the sequences of SEQ ID NOs: 7, 8, 17 and 18 of present claim 13, and the sequences of SEQ ID NOs: 27, 28, 37 and 38 of present claim 14 are supported by PCT/IL2022/050995. Thus, the effective filing date of present claims 13 and 14 is that of PCT/IL2022/050995 which is 09/14/2022.
Specification
The disclosure is objected to because of the following informalities: The current application was filed after July 1, 2022, thus the WIPO Standard ST.26, Sequence Listing in XML format, applies to sequence disclosures. See 37 CFR § 1.831. An ST.26 Sequence Listing in XML must not include any sequences having fewer than 10 specifically defined nucleotides, or fewer than 4 specifically defined amino acids. See 37 CFR § 1.831(j).
The sequences of SEQ ID NOs: 5, 15, 25 and 35 are replaced with “000” in the Sequence Listing in XML because the sequences are less than 4 amino acid sequences. Furthermore, the specification does not disclose the sequences of SEQ ID NOs: 5, 15, 25 and 35.
Claim Rejections - 35 USC § 112
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 – 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.
The following quotation from section 2163 of the Manual of Patent Examination Procedure (MPEP) is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice... reduction to drawings...or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See BU Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 1 – 24 are rejected as lacking adequate descriptive support for a possession of a generic multispecific antibody comprising a first antigen binding moiety, which specifically binds to an immune checkpoint protein on intratumor T cells and a second antigen binding moiety which specifically binds to a conventional dendritic cell 1 (cDC1). The specification presents PD-1/cDC1 BiSE that target cDC1-restricted surface markers XCR1 or CLEC9A in Examples 2 – 4, p. 41 – 43. No other examples, such as BiSE specifically binding to other immune checkpoint proteins on intratumor T cells and binding to other cDC1-restricted antigens, are provided.
Furthermore, in Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the
Supreme Court, held that claims drawn to a genus of monoclonal antibodies, which were functionally claimed by their ability to bind to a specific protein, PCSK9, were invalid due to lack of enablement. The claims at issue were functional, in that they defined the genus by its function (the ability to bind to specific residues of PCSK9) as opposed to reciting a specific structure (the amino acid sequence of the antibodies in the genus). See MPEP 2164.01.
Presently, the claimed antibody is only defined by functional properties: its ability to bind an immune checkpoint protein on intratumor T cells and a cDC1. In view of the fact patterns detailed in Amgen v. Sanofi, the Applicant is not in possession of such an antibody which can bind to any T-cell immune checkpoint protein and any cDC1 epitope as presented by the claims.
Regarding claims 6 – 9, the sequences of SEQ ID NOs: 5, 15, 25 and 35 are not disclosed in the specification. Because an ST.26 Sequence Listing in XML must not include any sequences having fewer than 10 specifically defined nucleotides, or fewer than 4 specifically defined amino acids (see 37 CFR § 1.831(j)), the sequences of SEQ ID NOs: 5, 15, 25 and 35 have each been replaced with a “000”. Neither the foreign document IL 286430 nor the PCT/IL2022/050995 application discloses the sequences of SEQ ID NOs: 5, 15, 25 and 35. Thus, SEQ ID NOs: 5, 15, 25 and 35 are not supported by the present application.
Providing SEQ ID NOs that represent specific sequences, with each position of the sequence defined with a specific amino acid, for both the first and second antigen binding moieties of the claimed multispecific antibody that are supported by the specification can provide sufficient structure(s) for claims 1 – 24.
In view of this uncertainty and the lack of a representative number of examples of the claimed genus, the claims are rejected for lack of adequate written description support.
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 6 – 9 and 23 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 6 – 9 recites the sequences of SEQ ID NOs: 5, 15, 25 and 35, respectively, which are not disclosed in the specification. Because an ST.26 Sequence Listing in XML must not include any sequences having fewer than 10 specifically defined nucleotides, or fewer than 4 specifically defined amino acids (see 37 CFR § 1.831(j)), the sequences of SEQ ID NOs: 5, 15, 25 and 35 have each been replaced with a “000”. Neither the foreign document IL 286430 nor the PCT/IL2022/050995 application discloses the sequences of SEQ ID NOs: 5, 15, 25 and 35. Thus, SEQ ID NOs: 5, 15, 25 and 35 are not supported by the present application, and the sequences of SEQ ID NOs: 5, 15, 25 and 35 are indefinite.
Claim 23 recites “predetermined level”, which is a relative phrase, lacks a defined standard and fails to apprise a person of ordinary skill in the art of the invention's true scope. Neither the claims nor the specification defines what the “predetermined level” is. For the purposes of prior art, claim 23 will be interpreted to encompass the cancers of claim 24, as any cancer would be expected to have a given T cell: dendritic cell ratio above any predetermined level because, as claimed, the predetermined level is arbitrary, and with neither the claims nor the specification providing guidance on how to gauge its degree, it is generic and encompasses anything.
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.
(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.
Claims 1 – 5, 15 – 22 and 24 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by KLEY (WO 2019/032662 A1, published 02/14/2019; see PTO-892: Notice of References Cited) as evidenced by CARVEN (US 8354509 B2, published 01/15/2013; see PTO-892).
KLEY is directed to a Clec9A binding agent that comprises additional targeting moieties that bind to other targets (e.g. antigens, receptor) on tumor cells (see KLEY at p. 2, first paragraph) which provides improved therapies for diseases including cancer by modifying dendritic cell functions (See KLEY at the last paragraph of BACKGROUND, p. 1 ). KLEY teaches a multi-specific Clec9A binding agent that comprises a targeting moiety having an antigen recognition domain that specifically binds to a checkpoint marker expressed on a T cell, e.g. one or more of PD-1/PD- L1 or PD-L2, CD28/CD80 or CD86, CTLA4/ CD80 or CD86, ICOS/ICOSL or B7RP1 , BTLA/HVEM, KIR, LAG3, CD137/CD137L, OX40/OX40L, CD27, CD40L, TIM3/Gal9, and A2aR. See KLEY at p. 64, third paragraph. Thus, KLEY anticipates present claims 1 – 2 and 4 – 5.
Regarding claim 3, KLEY teaches that the disclosed multi-specific Clec9A binding agent has one or more targeting moieties directed against PD-1; that the PD1 targeting moiety comprises the anti-PD- 1 antibody pembrolizumab (aka MK-3475, KEYTRUDA), or fragments thereof; and that the humanized anti-PD-1 antibodies are disclosed in US 8,354,509 (CARVEN). See KLEY at p.64, second to last paragraph and p. 65, third paragraph from the bottom.
CARVEN is directed to antibodies which block the binding of human Programmed Death Receptor 1 (hPD-1) to its ligands (hPD-L1 or hPD-L2. See CARVEN at the abstract. Thus, KLEY as evidenced by CARVEN anticipates claim 3.
Regarding claim 15, KLEY teaches that the Clec9A binding agent is bispecific. See KLEY at the second paragraph under Multi-Specific Chimeras and Fusions with Signaling Agents, p. 54.
Regarding claim 16, KLEY teaches that the Clec9A binding agent is suitable for use in a patient having one or more of: cancer, infections, immune disorders, and/or autoimmune diseases. See KLEY at claim 17.
Regarding claim 17, KLEY teaches pharmaceutical compositions comprising the Clec9A binding agents and their use in the treatment of various diseases. See KLEY at the abstract.
Regarding claim 18, KLEY teaches a recombinant nucleic acid composition encoding the Clec9A binding agents. See KLEY at claim 15.
Regarding claims 19 – 21, KLEY teaches that nucleic acids encoding the Clec9A binding agent of the invention can be incorporated (ligated) into expression vectors, which can be introduced into host cells through transfection, transformation, or transduction techniques and that transformed host cells can be grown under conditions that permit the host cells to express the genes that encode the Clec9A binding agent. Furthermore, KLEY teaches that following expression, the protein can be harvested and purified using techniques well known in the art. See KLEY at p. 92, second and fourth paragraphs.
Regarding claim 22, KLEY teaches a method for treating cancer, comprising administering to a patient in need thereof an effective amount of a chimeric protein comprising a Clec9A binding agent. See KLEY at claim 34.
Regarding claims 23 – 24, KLEY teaches a method for treating cancer, comprising administering to a patient in need thereof an effective amount of a chimeric protein comprising a Clec9A binding agent. wherein the cancer is selected form one or more of basal cell carcinoma, biliary tract cancer; bladder cancer; bone cancer; brain and central nervous system cancer; breast cancer; cancer of the peritoneum; cervical cancer; choriocarcinoma; colon and rectum cancer; connective tissue cancer; cancer of the digestive system; endometrial cancer; esophageal cancer; eye cancer; cancer of the head and neck; gastric cancer (including gastrointestinal cancer); glioblastoma; hepatic carcinoma; hepatoma; intra-epithelial neoplasm; kidney or renal cancer; larynx cancer; leukemia; liver cancer; lung cancer (e.g., small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, and squamous carcinoma of the lung); melanoma; myeloma; neuroblastoma; oral cavity cancer (lip, tongue, mouth, and pharynx); ovarian cancer; pancreatic cancer; prostate cancer; retinoblastoma; rhabdomyosarcoma; rectal cancer; cancer of the respiratory system; salivary gland carcinoma; sarcoma; skin cancer; squamous cell cancer; stomach cancer; testicular cancer; thyroid cancer; uterine or endometrial cancer; cancer of the urinary system; vulval cancer; lymphoma including Hodgkin's and non- Hodgkin's lymphoma, as well as B-cell lymphoma (including low grade/follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate grade/follicular NHL; intermediate grade diffuse NHL; high grade immunoblastic NHL; high grade lymphoblastic NHL; high grade small non-cleaved cell NHL; bulky disease NHL; mantle cell lymphoma; AIDS-related lymphoma; and Waldenstrom's Macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALL); Hairy cell leukemia; chronic myeloblasts leukemia; as well as other carcinomas and sarcomas; and post-transplant lymphoproliferative disorder (PTLD), as well as abnormal vascular proliferation associated with phakomatoses, edema (e.g. that associated with brain tumors), and Meigs' syndrome. See KLEY at claims 34 – 36.
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 10 is rejected under 35 U.S.C. 103 as being unpatentable over KLEY as evidenced by CARVEN as applied to claims 1 – 5, 15 – 22 and 24 above, and further in view of ZHANG (US 2023/0151111 A1, filed 04/22/2021, published 05/18/2023; see PTO-892).
The teachings of KLEY are discussed above and fully incorporated here. Although KLEY teaches the limitations of present claim 1, from which present claim 10 depends, KLEY does not expressly teach that the Fc region of said multispecific antibody comprises a mutation that serves to reduce binding of said antibody to FcγRs.
According to the present application, “[t]he modified (mutant) Fc region has one or more mutations corresponding to one or more mutations in a human IgG heavy chain (SEQ ID NO: 41) selected from the group consisting of N297A, S267E (“SE”), S267E/L382F (“SELF”), G237D/P238D/P271G/A330R (“V9”), or G237D/P238D/H268D/P271G/A330R (“V11”) (SEQ ID NO:2), or (“V12”) (p. 21, first paragraph).
ZHANG is directed to an anti-CD73-anti-PD-1 bispecific antibody, a pharmaceutical composition thereof and a use thereof. See ZHANG at the abstract. ZHANG teaches that inducing mutations in the Fc segments of antibodies and eliminating their binding to FcγRIa can effectively inhibit the secretion of IL-8, thereby improving the safety and efficacy of the antibodies. See ZHANG at paragraph 0019.
ZHANG teaches mutations on Ig gamma-1 chain C region, which after the mutation, the bispecific antibody has a reduced affinity constant to FcγRIa, FcγRIIIa and/or C1q compared with that before the mutation and that one of the preferable mutation is N297A. See ZHANG at claim 16.
Thus, at the effective filing date of the present claims, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of KLEY and ZHANG. The artisan would have been motivated to make and use the multispecific antibody of claim 10 because KLEY teaches multispecific antibody comprising a first antigen binding moiety, which specifically binds to an immune checkpoint protein on intratumor T cells and a second antigen binding moiety which specifically binds to a cDC1 which provides improved therapies for diseases including cancer by modifying dendritic cell functions and ZHANG teaches that eliminating the binding of multispecific antibodies to FcγRIa can improve the safety and efficacy of the antibodies. The artisan would have a reasonable expectation of success that a multispecific antibody that binds an immune checkpoint protein on intratumor T cells and a cDC1 with Fc mutations that improve the safety and efficacy will be effective at treating cancer from the disclosures of KLEY and ZHANG.
Claims 11 – 12 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over KLEY as evidenced by CARVEN as applied to claims 1 – 5, 15 – 22 and 24 above, and further in view of DAHAN (WO 2021/149053 A1, published 01/19/2017, an IDS reference submitted 06/03/2024).
The teachings of KLEY are discussed above and fully incorporated here. Although KLEY teaches the limitations of present claim 1, from which present claims 11 – 12 and 14 each depend directly or indirectly, KLEY does not expressly teach that the limitations of present claims 11 – 12 and 14.
DAHAN is directed to a multispecific antibody comprising a first moiety, which binds and activates CD40, a second moiety, which specifically binds a dendritic cell (DC) and a third moiety comprising a modified Fc region of said multispecific antibody for enhancing specificity and affinity of binding to FcyRIIb. See DAHAN at claim 1. DAHAN teaches that the second moiety binds a DC marker Clec9a. See DAHAN at claim 3.
Regarding claim 11, DAHAN teaches that the disclosed multispecific antibody comprises knobs-into-holes mutations. See DAHAN at claim 10.
Regarding claim 12, DAHAN teaches mutations in the CH3 domain of a first antibody of a bispecific antibody comprising Y349C/T366S/L368A/Y407V and mutation in the CH3 domain of a second antibody of a multispecific antibody comprising S354C/T366W. See DAHAN at claim 11.
Regarding claim 14, DAHAN teaches the sequences of SEQ ID NOs: 27 and 28. DAHAN’s SEQ ID NO: 17 is identical to present SEQ ID NO: 27, and DAHAN’s SEQ ID NO: 18 is identical to present SEQ ID NO: 28. See Appendix.
Thus, at the effective filing date of the present claims, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of KLEY and DAHAN. The artisan would have been motivated to make and use the multispecific antibody of claims 11 – 12 and 14 because KLEY teaches a multispecific antibody comprising a first antigen binding moiety, which specifically binds to an immune checkpoint protein on intratumor T cells and a second antigen binding moiety which specifically binds to a cDC1 which provides improved therapies for diseases including cancer by modifying dendritic cell functions and DAHAN teaches a multispecific antibody that binds a cDC1. The artisan would have a reasonable expectation of success that a multispecific antibody that binds an immune checkpoint protein on intratumor T cells and a cDC1 will be effective at treating cancer from the disclosures of KLEY and DAHAN.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over KLEY as evidenced by CARVEN as applied to claims 1 – 5, 15 – 22 and 24 above, and further in view of TIPTON (WO 2017/011580 A2, published 01/19/2017, an IDS reference submitted 06/03/2024).
The teachings of KLEY are discussed above and fully incorporated here. Although KLEY teaches the limitations of present claim 1, from which claim 13 depends, KLEY does not teach that the first moiety comprises amino acid sequences of SEQ ID NOs: 17 and 18.
TIPTON is directed to isolated antibody or antigen binding fragment thereof (AB) that specifically binds to mammalian PD-1, wherein the AB has one or more of the characteristics selected from the group consisting of: (a) the AB inhibits binding of mammalian PD-1 to mammalian PDL1 with an EC50 value less than 5 nM; (b) the AB inhibits binding of mammalian PD-1 to mammalian PDL2 with an EC50 value less than 5 nM; and (c) the AB specifically binds to human PD-1 and cynomolgus monkey PD-1 for use in a method of treating cancer. See TIPTON at claims 1 and 95.
TIPTON teaches the sequences of SEQ ID NOs: 17 and 18. TIPTON’s SEQ ID NO: 546 teaches the sequence of present SEQ ID NO: 17 with 100% identity, and TIPTON’s SEQ ID NO: 1115 teaches the sequence of SEQ ID NO: 18 with 100% identity. See Appendix.
Thus, at the effective filing date of the present claims, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of KLEY and TIPTON. The artisan would have been motivated to make and use the multispecific antibody of claim 13 because KLEY teaches a multispecific antibody comprising a first antigen binding moiety, which specifically binds to an immune checkpoint protein on intratumor T cells and a second antigen binding moiety which specifically binds to a cDC1 which provides improved therapies for diseases including cancer by modifying dendritic cell functions and TIPTON teaches an antibody that binds PD-1 and effectively inhibits the binding of PD-1 to PDL1 and PDL2 for the treatment of cancer. The artisan would have a reasonable expectation of success that a multispecific antibody that binds an immune checkpoint protein on intratumor T cells and a cDC1 will be effective at treating cancer from the disclosures of KLEY and DAHAN.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 – 5, 15 – 22 and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8 – 20 of copending Application No. 17/870,876 in view of KLEY, CARVEN, ZHANG, DAHAN and TIPTON.
Copending claim 1 recites a multispecific antibody comprising a first moiety, which binds CD40, a second moiety, which specifically binds Clec9a and a third moiety comprising a modified Fe region of said multi specific antibody which comprises a mutation S267E ("SE"), S267E/L382F ("SELF"). G237D/P238D/P271IG/A330R ("V9"). G237D/P238D/H268D/P271IG/A330R ("Vt 1") aind/orE233D/G237D/P238D /H268D/P271G/A330R ("V12") corresponding to human IgG1 sequence (positions corresponding to SEQ ID NO: 1).
The main difference between the present claims and the copending claims is that the present claims recite a claimed multispecific antibody comprising a first antigen binding moiety, which specifically binds to an immune checkpoint protein on intratumor T cells and that the immune checkpoint protein is selected from the group consisting of PD-1, CTLA-4, TIGIT, LAG-3, TIM-3, ICOS, BTLA, 4-1BB, GITR and OX-40. However, KLEY, CARVEN, ZHANG, DAHAN and TIPTON teach this difference. The teachings of KLEY, ZHANG, DAHAN and TIPTON, and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 102 and 103 above.
Because the copending claims recite a multispecific antibody comprising a first moiety, which binds CD40, a second moiety, which specifically binds Clec9a, and KLEY teaches that the multispecific antibody binds an immune checkpoint protein such as PD-1, it would have been obvious to one having ordinary skill in the art to use the moiety targeting an immune checkpoint protein of KLEY’s multispecific antibody to arrive to the multispecific antibody of the present claims.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
APPENDIX
Alignment with SEQ ID NO: 17
BDN00724
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BDN00724 standard; protein; 451 AA.
XX
AC BDN00724;
XX
DT 09-MAR-2017 (first entry)
XX
DE Anti-mouse PD-1 antibody J43v2 mIgG2A HC, SEQ ID 546.
XX
KW PD-1 protein; antibody; antibody production; antibody therapy; cancer;
KW cytostatic; heavy chain; immune modulation;
KW programmed cell death protein 1; prophylactic to disease; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2017011580-A2.
XX
CC PD 19-JAN-2017.
XX
CC PF 13-JUL-2016; 2016WO-US042141.
XX
PR 13-JUL-2015; 2015US-0191902P.
PR 17-AUG-2015; 2015US-0205825P.
PR 15-FEB-2016; 2016US-0295314P.
PR 15-APR-2016; 2016US-0323543P.
PR 09-MAY-2016; 2016US-0333629P.
XX
CC PA (CYTO-) CYTOMX THERAPEUTICS INC.
XX
CC PI Tipton KA, West JW, Chan CM;
XX
DR WPI; 2017-06047C/16.
XX
CC PT New isolated antibody or its antigen binding fragment that specifically
CC PT binds to mammalian programmed cell death protein (PD-1), for treating,
CC PT alleviating a symptom of, or delaying the progression of disorder or
CC PT disease, e.g. cancer.
XX
CC PS Example 15; SEQ ID NO 546; 516pp; English.
XX
CC The present invention relates to a novel isolated antibody or antigen
CC binding fragment (AB) thereof that specifically binds to a mammalian
CC programmed cell death protein 1 (PD-1). The antibody having the
CC characteristics of: (a) the AB inhibits binding of mammalian PD-1 to
CC mammalian programmed death-ligand 1 (PDL1); (b) the AB inhibits binding
CC of a mammalian PD-1 to mammalian PDL2 with an EC50 value less than 5 nM;
CC and (c) the AB specifically binds to a human PD-1 and cynomolgus monkey
CC PD-1. The invention further claims: (1) an activatable antibody that
CC binds to a mammalian PD-1; (2) a conjugated activatable antibody
CC comprising the antibody; (3) a method for producing an activatable
CC antibody; (4) a method for reducing the binding of a ligand selected from
CC PDL1 or PDL2 to PD-1 on T cells; (5) a method for reducing immune
CC suppression; and (6) a method for treating, alleviating a symptom of, or
CC delaying the progression of a PDL1-mediated disorder such as cancer. The
CC present sequence is an anti-mouse PD-1 antibody J43v2 mIgG2A HC, useful
CC for preparing the antigen binding fragment (AB) for reducing immune
CC suppression and for treating cancer.
XX
SQ Sequence 451 AA;
Query Match 100.0%; Score 646; Length 451;
Best Local Similarity 100.0%;
Matches 121; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVRLLESGGGLVKPEGSLKLSCVASGFTFSDYFMSWVRQAPGKGLEWVAHIYTKSYNYAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVRLLESGGGLVKPEGSLKLSCVASGFTFSDYFMSWVRQAPGKGLEWVAHIYTKSYNYAT 60
Qy 61 YYSGSVKGRFTISRDDSRSMVYLQMNNLRTEDTATYYCTRDGSGYPSLDFWGQGTQVTVS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYSGSVKGRFTISRDDSRSMVYLQMNNLRTEDTATYYCTRDGSGYPSLDFWGQGTQVTVS 120
Qy 121 S 121
|
Db 121 S 121
Alignment with SEQ ID NO: 18
BDN01293
ID BDN01293 standard; protein; 142 AA.
XX
AC BDN01293;
XX
DT 09-MAR-2017 (first entry)
XX
DE Anti-PD-1 antibody J43 MP7-5 2001 VL, SEQ ID 1115.
XX
KW PD-1 protein; antibody; antibody production; antibody therapy; cancer;
KW cytostatic; immune modulation; light chain variable region;
KW programmed cell death protein 1; prophylactic to disease; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2017011580-A2.
XX
CC PD 19-JAN-2017.
XX
CC PF 13-JUL-2016; 2016WO-US042141.
XX
PR 13-JUL-2015; 2015US-0191902P.
PR 17-AUG-2015; 2015US-0205825P.
PR 15-FEB-2016; 2016US-0295314P.
PR 15-APR-2016; 2016US-0323543P.
PR 09-MAY-2016; 2016US-0333629P.
XX
CC PA (CYTO-) CYTOMX THERAPEUTICS INC.
XX
CC PI Tipton KA, West JW, Chan CM;
XX
DR WPI; 2017-06047C/16.
XX
CC PT New isolated antibody or its antigen binding fragment that specifically
CC PT binds to mammalian programmed cell death protein (PD-1), for treating,
CC PT alleviating a symptom of, or delaying the progression of disorder or
CC PT disease, e.g. cancer.
XX
CC PS Claim 60; SEQ ID NO 1115; 516pp; English.
XX
CC The present invention relates to a novel isolated antibody or antigen
CC binding fragment (AB) thereof that specifically binds to a mammalian
CC programmed cell death protein 1 (PD-1). The antibody having the
CC characteristics of: (a) the AB inhibits binding of mammalian PD-1 to
CC mammalian programmed death-ligand 1 (PDL1); (b) the AB inhibits binding
CC of a mammalian PD-1 to mammalian PDL2 with an EC50 value less than 5 nM;
CC and (c) the AB specifically binds to a human PD-1 and cynomolgus monkey
CC PD-1. The invention further claims: (1) an activatable antibody that
CC binds to a mammalian PD-1; (2) a conjugated activatable antibody
CC comprising the antibody; (3) a method for producing an activatable
CC antibody; (4) a method for reducing the binding of a ligand selected from
CC PDL1 or PDL2 to PD-1 on T cells; (5) a method for reducing immune
CC suppression; and (6) a method for treating, alleviating a symptom of, or
CC delaying the progression of a PDL1-mediated disorder such as cancer. The
CC present sequence is an anti-PD-1 antibody J43 MP7-5 2001 light chain
CC variable region (VL), useful for preparing the antigen binding fragment
CC (AB) for reducing immune suppression and for treating cancer.
XX
SQ Sequence 142 AA;
Query Match 100.0%; Score 573; Length 142;
Best Local Similarity 100.0%;
Matches 109; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 YELTQPPSASVNVGETVKITCSGDQLPKYFADWFHQRSDQTILQVIYDDNKRPSGIPERI 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 34 YELTQPPSASVNVGETVKITCSGDQLPKYFADWFHQRSDQTILQVIYDDNKRPSGIPERI 93
Qy 61 SGSSSGTTATLTIRDVRAEDEGDYYCFSGYVDSDSKLYVFGSGTQLTVL 109
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 94 SGSSSGTTATLTIRDVRAEDEGDYYCFSGYVDSDSKLYVFGSGTQLTVL 142
Alignment with SEQ ID NO: 27
BJR84007
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BJR84007 standard; protein; 116 AA.
XX
AC BJR84007;
XX
DT 02-SEP-2021 (first entry)
XX
DE Anti-XCR1 antibody MARX10 heavy chain variable region protein, SEQ 17 #1.
XX
KW XCR1 chemokine; antibody; antibody production; antibody therapy;
KW bladder cancer; bone tumor; breast tumor; cancer;
KW central nervous system tumor; colon tumor; colorectal tumor; cytostatic;
KW esophagus tumor; gastrointestinal tumor; head and neck tumor;
KW heavy chain variable region; immune stimulation; leukemia; liver tumor;
KW lung tumor; multiple myeloma; ovary tumor; pancreas tumor;
KW prostate tumor; renal tumor; sarcoma; skin cancer; stomach tumor;
KW testis tumor; therapeutic; thyroid tumor; uterine cervix tumor;
KW uterus tumor; viral infection; virucide.
XX
OS Mus sp.
XX
CC PN WO2021149053-A1.
XX
CC PD 29-JUL-2021.
XX
CC PF 21-JAN-2021; 2021WO-IL050064.
XX
PR 22-JAN-2020; 2020IL-00272194.
XX
CC PA (YEDA ) YEDA RES & DEV CO LTD.
XX
CC PI Dahan R, Salomon R;
XX
DR WPI; 2021-86978X/065.
XX
CC PT Multispecific antibody comprises first moiety, which binds and activates
CC PT CD40, second moiety, which specifically binds dendritic cell and third
CC PT moiety comprising modified Fc region of multispecific antibody.
XX
CC PS Claim 12; SEQ ID NO 17; 88pp; English.
XX
CC The invention relates to a novel multispecific antibody, useful for
CC treating cancer and chronic viral infection. The invention further
CC claims: 1) a method of preparing a multispecific antibody; 2) a method of
CC stimulating an immune response in a subject; and 3) a method of treating
CC cancer and chronic viral infection in a subject in need. The
CC multispecific antibody is useful for preparing for treating cancer
CC selected from bladder cancer, breast cancer, uterine/cervical cancer,
CC ovarian cancer, prostate cancer, testicular cancer, esophageal cancer,
CC gastrointestinal cancer, pancreatic cancer, colorectal cancer, colon
CC cancer, kidney cancer, head and neck cancer, lung cancer, stomach cancer,
CC germ cell cancer, bone cancer, liver cancer, thyroid cancer, skin cancer,
CC neoplasm of the central nervous system, lymphoma, leukemia, myeloma,
CC sarcoma, and virus-related cancer; and a chronic viral infection. Note:
CC The present sequence is described as SEQ ID NO:17 in the sequence
CC listing, but it differs from the sequence given as SEQ ID NO:17 in Figure
CC 1B (see BJR84072).
XX
SQ Sequence 116 AA;
Query Match 100.0%; Score 619; Length 116;
Best Local Similarity 100.0%;
Matches 116; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQQPGAELVKPGASVKLSCKASGYTFTNYWIHWMKQRPGQGLEWIGMIHPNSDNTKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQQPGAELVKPGASVKLSCKASGYTFTNYWIHWMKQRPGQGLEWIGMIHPNSDNTKY 60
Qy 61 NEKFKAKAILTVDKSSSTAYMQLSSLTSEDSAVYYCARFANDGAYWGQGTLVTVSS 116
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NEKFKAKAILTVDKSSSTAYMQLSSLTSEDSAVYYCARFANDGAYWGQGTLVTVSS 116
Alignment with SEQ ID NO: 28
BJR84008
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BJR84008 standard; protein; 112 AA.
XX
AC BJR84008;
XX
DT 02-SEP-2021 (first entry)
XX
DE Anti-XCR1 antibody MARX10 light chain variable region protein, SEQ 18 #1.
XX
KW XCR1 chemokine; antibody; antibody production; antibody therapy;
KW bladder cancer; bone tumor; breast tumor; cancer;
KW central nervous system tumor; colon tumor; colorectal tumor; cytostatic;
KW esophagus tumor; gastrointestinal tumor; head and neck tumor;
KW immune stimulation; leukemia; light chain variable region; liver tumor;
KW lung tumor; multiple myeloma; ovary tumor; pancreas tumor;
KW prostate tumor; renal tumor; sarcoma; skin cancer; stomach tumor;
KW testis tumor; therapeutic; thyroid tumor; uterine cervix tumor;
KW uterus tumor; viral infection; virucide.
XX
OS Mus sp.
XX
CC PN WO2021149053-A1.
XX
CC PD 29-JUL-2021.
XX
CC PF 21-JAN-2021; 2021WO-IL050064.
XX
PR 22-JAN-2020; 2020IL-00272194.
XX
CC PA (YEDA ) YEDA RES & DEV CO LTD.
XX
CC PI Dahan R, Salomon R;
XX
DR WPI; 2021-86978X/065.
XX
CC PT Multispecific antibody comprises first moiety, which binds and activates
CC PT CD40, second moiety, which specifically binds dendritic cell and third
CC PT moiety comprising modified Fc region of multispecific antibody.
XX
CC PS Claim 12; SEQ ID NO 18; 88pp; English.
XX
CC The invention relates to a novel multispecific antibody, useful for
CC treating cancer and chronic viral infection. The invention further
CC claims: 1) a method of preparing a multispecific antibody; 2) a method of
CC stimulating an immune response in a subject; and 3) a method of treating
CC cancer and chronic viral infection in a subject in need. The
CC multispecific antibody is useful for preparing for treating cancer
CC selected from bladder cancer, breast cancer, uterine/cervical cancer,
CC ovarian cancer, prostate cancer, testicular cancer, esophageal cancer,
CC gastrointestinal cancer, pancreatic cancer, colorectal cancer, colon
CC cancer, kidney cancer, head and neck cancer, lung cancer, stomach cancer,
CC germ cell cancer, bone cancer, liver cancer, thyroid cancer, skin cancer,
CC neoplasm of the central nervous system, lymphoma, leukemia, myeloma,
CC sarcoma, and virus-related cancer; and a chronic viral infection. Note:
CC The present sequence is described as SEQ ID NO:18 in the sequence
CC listing, but it differs from the sequence given as SEQ ID NO:18 in Figure
CC 1B (see BJR84073).
XX
SQ Sequence 112 AA;
Query Match 100.0%; Score 589; Length 112;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DVVVTQTPLSLPVSLGDPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPKLLIYKISNRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DVVVTQTPLSLPVSLGDPASISCKSSQSLVHSNGNTYLHWYLQKPGQSPKLLIYKISNRF 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQNTHVPYTFGGGTKLEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQNTHVPYTFGGGTKLEIK 112
Prosecution Insights