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 .
Election/Restrictions
Claims 1, 2, 5, 6, 8-10, 12, 13, 15, 16, 19, 21, 22, and 28, are allowable. Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement among inventions (i.e., Species A, a single and specific antibody, as set forth in the Office action mailed on 7 October 2025, is hereby withdrawn and additional anti-IGSF8 antibodies are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Priority
The instant application claims priority to PCT/CN2020/108129 filed 10 August 2020. The PCT/CN2020/108129 does not recite or contemplate the instantly elected anti-IGSF8 L2-01 antibody comprising HCDRs1-3 as Seq ID Nos: 643, 644, 646, LCDRs1-3 as Seq ID Nos: 652, 653, and 655, VH as Seq ID No: 703, and a VL as Seq ID No: 707 (see instant specification pg. 180, bottom; see PCT/CN2020/108129 specification pg. 127, table 1). Therefore, the priority date for the instant claims 1-2, 5-6, 8-10, 12-22, 25, 28-29, 145, and 146 is that of PCT/CN2021/111469 filed 9 August 2021.
Withdrawn Claim Objections
In view of Applicant’s amendments to claims 1, 6, 8, 18, 19, and 29 the claim objections over said claims are hereby withdrawn.
Withdrawn Claim Rejections
In view of Applicants’ amendments to claims 1, 2, claim 6 (in part; see below), 9, 12, 13, 14 (cancelled), 16, 17, 25, 29 (in part) the 35 USC 112(b) and 35 USC 112(d) rejections over said claims are hereby withdrawn.
In view of Applicants’ amendments to claim 25 the 35 USC 112(a) rejection for written description is hereby withdrawn.
New Claim Objections
Claim 17 is objected to because of the following informalities:
Claim 17 recites, “thereof; and, optionally (ii) recovering” in lines 6-7 and should recite, “thereof; and[[,]] optionally .
Appropriate correction is required.
Maintained Claim Rejections
The following rejections are amended as necessitated by amendment.
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.
Claim 18 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating cancer in a subject in need thereof, does not reasonably provide enablement for a method of modulating an immune response in a subject in need thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As a preliminary matter please note the following:
MPEP § 2111 instructs:
“The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005) expressly recognized that the USPTO employs the ‘broadest reasonable interpretation’ standard:
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The Patent and Trademark Office (‘PTO’) determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must ‘conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description.’ 37 CFR 1.75(d)(1).”
Likewise, MPEP § 2164.08 instructs:
“All questions of enablement are evaluated against the claimed subject matter. The focus of the examination inquiry is whether everything within the scope of the claim is enabled. Accordingly, the first analytical step requires that the examiner determine exactly what subject matter is encompassed by the claims.”
(emphasis added).
Claim 18 recites the following (emphasis added)
“A method of stimulating a T cell and/or NK cell in a subject in need thereof, the method comprising administering a therapeutically effective amount of the anti-IGSF8 monoclonal antibody or antigen-binding fragment thereof of claim 1 to the subject”
The specification defines “therapeutically effective amount” as an amount of a drug effective to treat a disease or disorder in a subject (see specification pg. 31, 1st para). The specification defines cancer as referring to a group of cells that exhibit abnormally high levels of proliferation and growth, including benign, premalignant, or malignant (see specification pg. 26, 3rd full para). While the specification is predominantly drawn to methods of treating cancer there are recitations of also treating an “infectious disease”, but no specific infectious or other disease is set forth (e.g., see specification pg. 55, 1st full para).
The specification discloses IGSF8 has been “speculated to regulate the roles of CD9 and CD81 in certain cellular functions, including cell migration and viral infection” and “as a potential tumor suppressor” and is “likely required for KAI1/CD82-mediated suppression of cancer cell migration” (see specification pg. 1, 3rd para). Applicant also discloses there remains a need to identify NK cell-suppressing, non-HLA ligands that may have been hijacked by cancer cells to evade NK cell-mediated killing in the tumor microenvironment, and reagent that can block suppression of NK cells” (see specification pg. 2, last full para).
IGSF8 is a novel cancer treatment target and is highly expressed in multiple cancer types specifically melanoma, cervical cancer, NSCLC, and colorectal cancer (see specification pg. 17, 2nd para). IGSF8 binds to primary NK cells through its D1 domain through the KIR family receptor KIR3DL2 (see specification pg. 18, 1st full para). Up regulation of IGSF8 allows tumors to evade NK cell-mediated immune surveillance of cancer by binding to KIR receptors on NK cells (see specification pg. 18, 2nd para). Plainly, the instant antibodies work by blocking IGSF8 on cancer cells from interacting with the KIR3DL1/2 receptors thereby inhibiting the inhibitory signal which leads to hyperactivation of NK cells; thereby, changing the tumor microenvironment. There is no guidance in the specification for a therapeutically effective amount of the claimed antibody which would stimulate a T cell and/or NK cell in a subject beyond cancer cells with increased expression of IGSF8.
Considering the guidance set forth above, the utility of the claimed method for stimulating a T cell and/or NK cell in a subject in need thereof of the instant claims would be understood by the skilled artisan to lie in treating cancer and infectious disease. By contrast the skilled artisan knowledgeable of the prior art and the teaching of the instant specification would not be interested in “stimulating a T cell and/or NK cell” in any given subject, e.g., a healthy subject, a subject with any disease/disorder, merely for the sake of doing so.
Applicant has demonstrated particular anti-IGSF8 antibodies with increased affinity and decreased Fc activity have better in vivo anti-tumor efficacy than those with reduced affinity and normal IgG1 or IgG4 activity (see specification pg. 195, Table 4, pg. 197, Table G, pg. 205, example 30). It is noted the instantly claimed antibodies do not bind mouse IGSF8 (see specification pgs. 202-203, table 5). Applicant has not provided an example of the instantly claimed antibodies stimulating a T cell and/or NK cell in the context with any other disease or disorder beyond cancer let alone in a healthy subject as encompassed by the instant claim language.
In the absence of such information the skilled artisan would not know how to use the instantly claimed anti-IGSF8 antibodies with any Fc region in a method of stimulating a T cell and/or NK cell in a healthy subject or a subject any disease/disorder using a therapeutically effective amount.
Applicants’ arguments filed 24 June 2026 (referred to herein as Remarks) have been fully considered but they are not persuasive.
Applicants argue amendments to the claims are sufficient to overcome the 35 USC 112(a) rejection (see Remarks pg. 12 middle section). This is not persuasive for the reasons set forth above.
New Matter
Claim 25 is 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 25 is drawn to wherein the cancer is “a cancer infiltrated with immune cells expressing a receptor to IGSF8 selected from the group consisting of KIR3DL1, KIR3DL2, KLRC1, KLRD1, or a combination thereof” (see last three lines). The specification does not disclose or contemplate a genus of cancers infiltrated with any immune cell expressing the claimed receptors or combinations thereof. The specification discloses the IGSF8 binds to KLRC1/D1 heterodimers (see specification pg. 169, 3rd full para). Therefore, “a cancer infiltrated with immune cells expressing a receptor to IGSF8 selected from the group consisting of KIR3DL1, KIR3DL2, KLRC1, KLRD1, or a combination thereof” reaches beyond the specification as originally filed. It is noted Applicants have not pointed to any specific place for support for the claim amendment (see Remarks pg. 11, 2nd para). Examiner suggests removing the clause and ending the claim with “thymoma”.
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.
Claims 6, 20, and 29 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 6 is drawn to wherein the antibody of claim 1 has a Fd (see line 4). Claim 1 is drawn to antibodies or antigen binding fragments thereof that necessarily comprise a VH and VL. Therefore, it is unclear how the antibody can have the Fd, when this structures necessarily comprises a heavy chain variable region only.
Claim 20 is drawn to “a second therapy or therapeutic agent comprising”. It is unclear if “comprising is associated with both the second therapy and therapeutic agent, or alternatively, is limited to the therapeutic agent.
Claim 29 is drawn several recitations of parentheticals. For example, “(non-antibody) peptide inhibitor”. It is unclear if what is recited in the paratheses is a limitation, an alternative name for a structure, or an example. Examiner recommends amending the claim to remove parenthetical. It is noted the claim has been amended to remove parentheticals regarding products but has not amended the parenthetical associated with the claimed structure.
Claim 29 recites the limitation "said second therapeutic agent" in line 10. There is insufficient antecedent basis for this limitation in the claim. It is unclear if “second” is intended to refer to “second therapy” or the “therapeutic agent” as recited in claim 20.
Applicants’ arguments filed 24 June 2026 (referred to herein as Remarks) have been fully considered but they are not persuasive.
Applicants argue amendments to the claims are sufficient to overcome the 35 USC 112(a) rejection (see Remarks pg. 14 bottom 3rd of page). This is not persuasive for the reasons set forth above.
Proposed Examiner’s Amendment
17. A method of producing a monoclonal antibody or antigen-binding fragment thereof, the method comprising culturing the host cell of claim 16 capable of expressing said monoclonal antibody or antigen-binding fragment thereof under a condition suitable to express said monoclonal antibody or antigen binding fragment thereof; and[[,]] optionally
18. cancelled.
20. The method of claim 19, further comprising administering to the subject an effective amount of a
25. The method of claim 19, wherein the cancer is melanoma, cervical cancer, lung cancer, non-small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, colorectal cancer, lymphoma, B cell lymphoma, diffused large B-cell lymphoma (DLBCL), leukemia, chronic lymphocytic leukemia (CLL), and Acute Myeloid Leukemia (AML), bladder cancer, breast cancer, head and neck carcinoma, head-neck squamous cell carcinoma, prostate adenocarcinoma (PRAD), uterine corpus endometrial carcinoma (UCEC), thyroid cancer, uterine cancer, esophagus cancer, liver cancer, ganglia cancer, renal cancer, pancreatic cancer, pancreatic ductal carcinoma, ovarian cancer, prostate cancer, gliomas, glioblastoma, neuroblastoma, or thymoma
29. The method of claim 20, wherein:
the immune checkpoint inhibitor is an antibody or antigen-binding fragment thereof specific for PD-1, PD-L1, PD-L2, LAG3, TIGIT, TIM3, NKG2A, CD276, or VTCN1;
the immune checkpoint inhibitor is an anti-PD-1 antibody; or
the immune checkpoint inhibitor is an anti-PD-L1 antibody
145. The method of claim 29, wherein the immune checkpoint inhibitor is cemiplimab, nivolumab, pembrolizumab, avelumab, durvalumab, atezolizumab, KN035, or CK-301
It is noted the Examiner has offered two examiner’s amendments for allowable subject matter (i.e., non-final, interview summary amendment above) with a third presented above. Applicant has declined both offered amendments.
Conclusion
Claims 1, 2, 5, 6, 8-10, 12, 13, 15, 16, 19, 21, 22, and 28 are allowed.
Claims 17, 18, 20, 25, 29, 145, and 146 are not allowed.
Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HILARY ANN PETRASH whose telephone number is (703)756-4630. The examiner can normally be reached Monday-Friday 8:30-4:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571)-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/H.A.P./Examiner, Art Unit 1644
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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