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 .
Claims Status
The amendments and remarks filed 06/30/2026 are acknowledged.
Claims 2-9, 12, and 15-19 are pending.
Claims 2-8 and 15 are amended.
Claims 1, 10-11, and 13-14 are canceled.
Claims 16-19 are new.
Claims 2-9, 12, and 15-19 are under examination.
Withdrawn
The objection to the specification is withdrawn. Applicant has amended the specification to overcome the rejection.
The objections to claims 4, 8, and 15 are withdrawn. Applicant has amended the claims to overcome the objections.
The rejections of claims 1 and 8 under 35 U.S.C. 112(b) are withdrawn. Applicant has canceled claim 1 and amended claim 8 to overcome the rejections.
The rejections of claims 2-9, 12, and 15 under 35 U.S.C. 112(a) are withdrawn. Applicant has amended the claims to overcome the rejections.
Claim Objections
Claims 5 is objected to as being dependent upon a rejected base claim (i.e. claim 2), but would be allowable if the below corrections are made and if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Maintained Rejections
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.
This rejection has been modified solely to address the amendments to claims 4 and 15 and the addition of new claims 16-19.
Claims 2, 4, 6-9, 12, and 15-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-8, 11, and 14-15 of copending Application No. 18/260,435 (‘435; reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 2 of the instant application, claim 1 of ‘435 teaches a bispecific antibody comprising a first antigen-binding functional region that specifically binds to PD-L1 and a second antigen-binding functional region that specifically binds to 4-1BB, wherein the first antigen-binding functional region that specifically binds PD-L1 comprises: (A) a heavy chain variable region, comprising (a) HCDR1, which comprises the amino acid sequence set forth in SEQ ID NO: 15, (b) HCDR2, which comprises the amino acid sequence set forth in SEQ ID NO: 16, and (c) HCDR3, which comprises the amino acid sequence set forth in SEQ ID NO: 17; and (B) a light chain variable region, comprising (a) LCDR1, which comprises the amino acid sequence set forth in SEQ ID NO: 18, (b) LCDR2, which comprises the amino acid sequence set forth in SEQ ID NO: 19, and (c) LCDR3, which comprises the amino acid sequence set forth in SEQ ID NO: 20, and claims 2 and 3 of ‘435 teach wherein the second antigen-binding functional region that specifically binds to 4-1BB comprises (A) a heavy chain variable region, comprising (a) HCDR1, which comprises the amino acid sequence set forth in SEQ ID NO: 21, (b) HCDR2, which comprises the amino acid sequence set forth in SEQ ID NO: 22, and (c) HCDR3, which comprises the amino acid sequence set forth in SEQ ID NO: 23; and (B) a light chain variable region, comprising (a) LCDR1, which comprises the amino acid sequence set forth in SEQ ID NO: 24, (b) LCDR2, which comprises the amino acid sequence set forth in SEQ ID NO: 25, and (c) LCDR3, which comprises the amino acid sequence set forth in SEQ ID NO: 26.
SEQ ID NOs: 21-23 for the HCDRs 1-3 and SEQ ID NOs: 24-26 for the LCDRs 1-3 of ‘435 have 100% sequence identity to SEQ ID NOs: 4-6 for the HCDRs 1-3 and SEQ ID NOs: 1-3 for the LCDRs 1-3 of instant claim 2.
Regarding claims 4 and 16, claim 14 of ‘435 teaches the bispecific antibody of claim 1, comprising a second heavy chain/second light chain pair that specifically binds to 4-lBB, wherein: the second heavy chain has a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 12, and a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 14; and the second light chain has a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 10, and a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO: 4.
SEQ ID NO: 4 of ‘435 is a human kappa CL domain as evidenced by Presta (US Patent No. 6,121,022; instant PTO-892) [see sequence results attached] and SEQ ID NO: 14 is an IgG1 heavy chain constant region as evidenced by Liu (WO2018177324; instant PTO-892) [see sequence results attached]. Therefore, this meets the limitations of claim 4 and 16 requiring that the heavy chain constant region sequence of the antibody is the constant region sequence of IgG1 and the light chain constant region sequence of the antibody is the constant region sequence of kappa chain.
Regarding claims 6 and 7 of the instant application, claims 5 and 6 of ‘435 teach that the second antigen-binding functional region that specifically binds to 4-1BB comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 12, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 10.
SEQ ID NO: 12 of ‘435 has 100% sequence identity to SEQ ID NO: 12 of the instant claim and SEQ ID NO: 10 of ‘435 has 100% sequence identity to SEQ ID NO: 11 of the instant claim.
Regarding claims 8 and 17 of the instant application, claims 7 and 8 of ‘435 teach that the second antigen-binding functional region [that specifically binds to 4-1BB] is a Fab fragment.
Regarding claim 9 of the instant application, claim 15 of ‘435 teaches an isolated polynucleotide encoding the bispecific antibody of claim 1.
Regarding claim 12 of the instant application, claim 19 of ‘435 teaches a composition comprising the bispecific antibody of claim 1 and a pharmaceutically acceptable carrier.
Regarding claims 15, 18, and 19 of the instant application, claim 27 of ‘435 teaches a method of treating cancer comprising administering to a subject in need thereof the bispecific antibody of claim 1, and claim 29 of ‘435 teaches wherein the cancer is selected from the group consisting of leukemia, lymphoma, myeloma, brain tumor, head and neck squamous cell cancer, non-small cell lung cancer, nasopharyngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, gallbladder cancer, liver cancer, colorectal cancer, breast cancer, ovarian cancer, cervical cancer, endometrial cancer, uterine sarcoma, prostate cancer, bladder cancer, renal cell cancer, melanoma, small cell lung cancer and bone cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 2-4, 6-9, 12, and 15-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-8, 11, and 14-15 of copending Application No. 18/260,435 (‘435; reference application), as applied to claims 2, 4, 6-9, 12, and 15-19 above, and further in view of Jolliffe, 1992 (instant PTO-892).
The teachings of ‘435 are above.
However. ‘435 does not specifically teach that the 4-1BB antibody or antigen-binding fragment thereof is a humanized antibody.
Regarding claim 3 of the instant application, Jolliffe teaches that by humanizing an antibody, the antibody can retain the specificity and biological effects but can be nonimmunogenic in humans, and additionally, the antibody effector functions can be improved through manipulation of the antibody constant region genes [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the antibody of ‘435 to specifically be a humanized antibody. One would have been motivated to create a humanized antibody because Jolliffe teaches that by humanizing an antibody, the antibody can retain the specificity and biological effects but can be nonimmunogenic in humans, and additionally, the antibody effector functions can be improved through manipulation of the antibody constant region genes.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
The double patenting rejections over copending Application No. 18/260,435 (reference application) are maintained. Applicant argues on page 10 of the remarks that the claims of the co-pending application are directed to a bispecific antibody, and while it comprises the same six CDRS of the anti-4-1BB antibody as those instantly claimed, it also comprises an anti-PD-L1 antibody. Applicant further argues that the subject matter of the present application is an isolated anti-human 4-1BB antibody, which does not comprise any other antibody components targeting other antigens, and therefore, the scope of the instant claims are patentably distinct from the claims of US 18/260,435. This is not found persuasive because in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the anti-human 4-1BB antibody does not comprise any other antibody components targeting other antigens) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Additionally, the use of “comprises” in instant claim 2 encompasses any other embodiment so long as it has the claimed anti-human 4-1BB antibody, and therefore, the claim language of the reference application meets each and every limitation of the instant claim. Further, the specification does not have a special definition of “isolated” and the instant specification states that the invention also includes a bispecific antibody wherein the anti-4-1BB binding region is part of a bivalent scaffold [see page 19, lines 23-30 of the instant specification].
Note: The Office notes that, as of the date that this office action is written (7/22/2026), a Notice of Allowance has been issued for the ‘435 Application (on 4/14/2026) but a patent has not yet been issued.
New Grounds of Rejection Necessitated by Amendment
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 16 and 19 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 16 recites the limitation “wherein the heavy chain constant region sequence of the antibody is the constant region sequence of lgG1 or IgG4, and/or and the light chain constant region sequence of the antibody is the constant region sequence of K chain”. It is unclear based on the wording of “and/or and” if only the first limitation before the “and/or and” is required or if both the limitations before and after the “and/or and” are required. Therefore, the scope of this claim is indefinite.
Note: For examination purposes, the Examiner is interpreting the claim with the narrower claim scope requiring both of the limitations listed before and after the “and/or and”.
Claim 19 recites the limitation “wherein the tumors are one or more selected from the group consisting of leukemia, lymphoma, myeloma…”. Leukemia is a cancer of the blood and bone marrow and myeloma is a form of blood cancer that starts in the bone marrow, and which do not form solid masses or tumors. Therefore, “leukemia” and “myeloma” do not fall under the scope of “tumors” and thus, the scope of this claim is indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 19 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 19, which depends from claim 18 requiring that the 4-1BB-mediated diseases or disorders are tumors, recites the limitation “wherein the tumors are one or more selected from the group consisting of leukemia, lymphoma, myeloma…”. Leukemia is a cancer of the blood and bone marrow and myeloma is a form of blood cancer that starts in the bone marrow, and which do not form solid masses or tumors. Therefore, claim 19 does not include all the limitations of claim 18 because leukemia and myeloma are not tumors. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claims allowed.
Applicant's 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 Brittney E Donoghue whose telephone number is (571)272-9883. The examiner can normally be reached Mon - Fri 7:30 - 3:30.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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