Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
Applicant’s amendment filed February 24, 2026 is acknowledged. Claims 1-239 are canceled. Claims 240-244, 247, 250-258 are amended. Claims 259-275 are newly added. Claims 240-258 and new claims 259-275 are pending in this application. Claims 248-251 and 253-257 and new claims 268-272 and 275 are withdrawn without traverse (filed 09/02/2025) from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 2, 2025.
Newly submitted claims 268-272 and 275 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Newly submitted claims 268-272 and 275 are directed to polynucleotides, vectors, host cells (Group I) and methods of treatment (Group III), which are independent or distinct from the invention originally claimed and are withdrawn without traverse from consideration (filed 09/02/2025).
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 268-272 and 275 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Applicant’s request for rejoinder and allowance of withdrawn claims 248-251 and 253-257 is moot because instant claims are still rejected.
Claims 240-247, 252, 258-267 and 273-274 are under examination with respect to SEQ ID NOs: 72 and 78 for VH and VL, SEQ ID NOs: 6 for IgG H1, SEQ ID NO:8 for IgG2 CH1, the sequence of KCSPG for epitope and agonist anti-PD1 agent for additional therapeutic agent in this office action.
Applicant’s arguments filed on February 24, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Specification
The objection to the specification is withdrawn in response to Applicant’s amendment to the specification.
Claim Rejections/Objections Withdrawn
The objection to claim 244 is withdrawn in response to Applicant’s amendment to the claim.
The rejection of claims 240-247 on the basis that it contains an improper Markush grouping of alternatives is withdrawn in response to Applicant’s amendment to the claims and arguments on p. 14 of the response.
The rejection of claims 240-243, 245, 247, 252 and 258 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 is withdrawn in response to Applicant’s amendment to the claims.
The rejection of claim 252 under 35 U.S.C. 103 as being unpatentable over ) in view of Tam et al. (Sci. Transl. Med. 2019; 11: eaax0720: 1-15) is withdrawn in response to Applicant’s amendment to the claim.
Claim Rejections/Objections Maintained
In view of the amendment filed on February 24, 2026, the following rejections are maintained.
Claim Objections
Claims 243 and 263 are objected to because of the following informalities: The recitations “CRD1”, “CRD2” and “CRD3” in claims 243 and 263 are not unique or common abbreviations in the art. Applicants are required to spell out “CRD1”, “CRD2” and “CRD3” at the first usage. Appropriate correction is required.
Claims 252 and 258 are objected to under 37 CFR 1.75(c), as being of improper dependent form for failing to further limit the subject matter of a previous claim. Claims 252 and 258 depend from claim 240. However, Claim 240 is only directed to an antibody or antigen-binding fragment thereof, and does not claim polynucleotides, vectors or host cells, which are non-elected subject matter. Applicant is required to cancel the claim(s), or amend the claim(s) to place the claim(s) in proper dependent form, or rewrite the claim(s) in independent form.
Improper Markush Grouping
Claims 252, 258 and 274 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 14 of the response, Applicant argues that the Markush grouping in claim 240 is proper because SEQ ID NOs: 72-77 share the recited SEQ ID NOs: for CDR-H1-3 and SEQ ID NOs:78-83 share the same recited SEQ ID NOs: for CDR-L1-3.
Applicant’s arguments related to sharing the same sequences of CDR-H1-3 for SEQ ID NOs: 72-77 and the same sequences of CDR-L1-3 for SEQ ID NOs: 78-83 are fully considered and found persuasive. However, the Markush grouping of different agents including antibodies/antigen-binding fragments thereof, polynucleotides, vectors and host cells in claims 252 and 258 and the Markush grouping of different agents recited in claim 274 are still improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The recited alternative species do not share a single structural similarity, as each species recited in the Markush group has a different chemical structure because the structures and compositions of the recited antibodies/antigen-binding fragments are different from those of polynucleotides/vectors or host cells, and the structures and compositions of the immunotherapy agent recited in claim 274 are different from each other, each type of agents or molecules/components has different activities, functions and effects. Thus, the different agents/components recited in the Markush grouping do not share a single structural similarity or biological activity. Accordingly, different agents or molecules/components recited in the Markush group do not share a single structural similarity essential to this activity. See MPEP § 706.03(y).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
10. 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 244, 246 and 264 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. The rejection is maintained for the reasons made of record and the reasons set forth below.
Claims 244, 264 encompass a genus of polyclonal antibody, a genus of human antibody, a genus of bispecific antibody, a genus of multi-specific antibody, a genus of dual-variable immunoglobulin domain, a genus of diabody, a genus of triabody, a genus of antibody-like protein scaffold, a genus of tandem scFv (taFv).
Claim 246 encompasses a genus of single-chain polypeptide that competitively inhibits the binding of human TNFR2 to the single-chain polypeptide of claim 245.
Response to Arguments
On p. 15 of the response, Applicant argues that the rejection has been overcome in view of amendment to claim 240 by reciting 6CDRs corresponding to the claimed anti-TNFR2 antibodies.
Applicant's arguments related to claim 240 by reciting 6CDRs have been fully considered and they are persuasive. However, based on MPEP §2163, MPEP §§2163.01-2163.03, the specification fails to provide sufficient description or information or evidence to demonstrate that Applicant is in possession of the claimed genus of polyclonal antibody, human antibody, bispecific antibody, multi-specific antibody, dual-variable immunoglobulin domain, diabody, triabody, tandem scFv (taFv) or single-chain polypeptide competitively inhibiting the binding of human TNFR2 recited in claims 244, 246 and 264 because:
i. The structural and functional relationship or correlation between the claimed genus of polyclonal antibody, human antibody, bispecific antibody, multi-specific antibody, dual-variable immunoglobulin domain, diabody, triabody, tandem scFv (taFv) or single-chain polypeptide competitively inhibiting the binding of human TNFR2 and the anti-TFNR2 having defined SEQ ID NOs: for CDR-H1-3 and CDR-L1-3 or VH and VL is unknown.
ii. The specification has not disclosed sufficient species for the broad genus of polyclonal antibody, human antibody, bispecific antibody, multi-specific antibody, dual-variable immunoglobulin domain, diabody, triabody, tandem scFv (taFv) or single-chain polypeptide competitively inhibiting the binding of human TNFR2.
iii. The specification has provided no structures or sequences sufficiently detailed to show that he/she was in possession of the claimed invention as a whole. There was no known or disclosed correlation between the required function (binding to TNFR2) and any particular structure or sequence for polyclonal antibody, human antibody, bispecific antibody, multi-specific antibody, dual-variable immunoglobulin domain, diabody, triabody, tandem scFv (taFv) or single-chain polypeptide competitively inhibiting the binding of human TNFR2.
The specification fails to teach the detailed structures and sequences and characteristics for the claimed genus of structurally and functionally undefined polyclonal antibody, human antibody, bispecific antibody, multi-specific antibody, dual-variable immunoglobulin domain, diabody, triabody, tandem scFv (taFv) or single-chain polypeptide competitively inhibiting the binding of human TNFR2.
The specification' s general reference to “polyclonal antibody, human antibody, bispecific antibody, multi-specific antibody, dual-variable immunoglobulin domain, diabody, triabody, tandem scFv (taFv) or single-chain polypeptide competitively inhibiting the binding of human TNFR2” does not clearly suggest a particular sequence of structurally and functionally undefined polyclonal antibody, human antibody, bispecific antibody, multi-specific antibody, dual-variable immunoglobulin domain, diabody, triabody, tandem scFv (taFv) or single-chain polypeptide competitively inhibiting the binding of human TNFR2.
The specification fails to teach what other structures/amino acid sequences can or cannot be included/changed in the claimed genus of structurally and functionally undefined polyclonal antibodies, human antibodies, bispecific antibodies, multi-specific antibodies, dual-variable immunoglobulin domains, diabodies, triabodies, tandem scFv (taFv) or single-chain polypeptides competitively inhibiting the binding of human TNFR2 in order to preserve the activity of the anti-TNFR2 having defined sequences of recited SEQ ID NOs: for CDR-H1-3 and CDR-L1-3 or VH and VL.
The specification provides no identification of any particular portion of the structure that must be conserved. The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of polyclonal antibody, human antibody, bispecific antibody, multi-specific antibody, dual-variable immunoglobulin domain, diabody, triabody, tandem scFv (taFv) or single-chain polypeptide competitively inhibiting the binding of human TNFR2. There is no description of the conserved regions which are critical to the function of the genus claimed. There is no description of the sites at which variability may be tolerated and there is no information regarding the relation of structure of polyclonal antibodies, human antibodies, bispecific antibodies, multi-specific antibodies, dual-variable immunoglobulin domains, diabodies, triabodies, tandem scFv (taFv) or single-chain polypeptides competitively inhibiting the binding of human TNFR2 to the function of the anti-TNFR2 antibodies with defined SEQ ID NOs.
Since the common characteristics/features of other polyclonal antibodies, human antibodies, bispecific antibodies, multi-specific antibodies, dual-variable immunoglobulin domains, diabodies, triabodies, tandem scFv (taFv) or single-chain polypeptides competitively inhibiting the binding of human TNFR2 are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention in view of Rudikoff et al. (see p. 1979; Proc. Natl. Acad. Sci. USA 1982 Vol. 79: page 1979, cited previously), Burgess et al. (J of Cell Bio. 1990, 111:2129-2138, cited previously), Bowie et al. (see col 2, p. 1306, Bowie et al. Science, 1990, 247:1306-1310, cited previously), Pawson et al. (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452, cited previously), Alaoui-lsmaili et al. (see p. 502, right col., 2th paragraph; Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507, cited previously), Guo et al. (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210, cited previously), MacCallum et al. (see p. 73, J. Mol. Biol.,1996; 262: 732-745, cited previously). Pascalis et al. (see p. 3079-3080 ; The Journal of Immunology, 2002; 169: 3076-3084, cited previously), Casset et al. (page 202, left col.; BBRC, 2003; 307: 198-205, cited previously), Vajdos et al. (see p. 416, left col ; J. Mol. Biol. 2002; 320: 415-428 Holm et al.(Mol. Immunol., 2007; 44: 1075-1084, cited previously) , Chen et al. (see p. 866 ; J. Mol. Bio., 1999; 293: 865-881, cited previously) and Wu et al. (see p. 152, left col. ; J. Mol. Biol., 1999; 294:151-162, cited previously).
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of polyclonal antibodies, human antibodies, bispecific antibodies, multi-specific antibodies, dual-variable immunoglobulin domains, diabodies, triabodies, tandem scFv (taFv) or single-chain polypeptides competitively inhibiting the binding of human TNFR2.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polyclonal antibodies, human antibodies, bispecific antibodies, multi-specific antibodies, dual-variable immunoglobulin domains, diabodies, triabodies, tandem scFv (taFv) or single-chain polypeptides competitively inhibiting the binding of human TNFR2, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 and Centocor v. Abbott, 636 F.3d1341 (Fed. Cir. 2011) and AbbVie v. Janssen, 759 F.3d 1285 (Fed. Cir.2014). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed polyclonal antibody, human antibody, bispecific antibody, multi-specific antibody, dual-variable immunoglobulin domain, diabody, triabody, tandem scFv (taFv) and single-chain polypeptide competitively inhibiting the binding of human TNFR2 have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
Accordingly, the rejection of claims 244, 246 and 264 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 is maintained.
Claim Rejections - 35 USC § 102
11. 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 240, 242-247, 252, 258, 262-264 and 266-267 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Thompson (US10988543, issued Apr 27, 2021, priority Nov 15, 2015). The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 240, 242-247, 252, 258, 262-264 and 266-267 are drawn to an anti-TNFR2 antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof comprises SEQ ID NOs: 84-86 for CDR-H1-3 respectively, SEQ ID NOs:87 or 88 and 89-90 for CDR-L1-3, and wherein a VH having at least 96% sequence identity to the amino acid sequence of any one of SEQ ID NOs:72 (elected)-77; and/or and a VL having at least 91% sequence identity to SEQ ID NOs:78 (elected)-83.
Response to Arguments
On p. 15-17 of the response, Applicant argues that based on the alignment performed using BLAST®, SEQ ID NO:7 disclosed by Thompson is 95.8% identical to instant SEQ ID NO:72 and SEQ ID NO:9 disclosed by Thompson is only 90.7% identical to instant SEQ ID NO:78.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2131, Thompson (US10988543) does teach the claimed anti-TNFR2 antibody or antigen-binding fragment thereof because:
i. The query match of instant SEQ ID NO:72 to the sequence of SEQ ID NO: 7 of Thompson is 97.5%, which meets the limitation “at least 96% identical to instant SEQ ID NO:72” recited in instant claim 240; and the query match of instant SEQ ID NO:78 to the sequence of SEQ ID NO:9 is 93.6% and thus meets the limitation “at least 91% identical to instant SEQ ID NO:78” recited in instant claim 240 (see the sequence alignment below; col. 8, lines 3-14; col. 13, line 53-col.14). The SEQ ID NO:7 (VH) of Thompson comprises the sequences of recited SEQ ID NOs:84-86 for CDR-H1-3 and the SEQ ID NO:9 (VL) of Thompson comprise sequences of SEQ ID NOs: 87 and 89-90 for CDR-L1-3, which also meets the limitation “comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 84; a CDR-H2…SEQ ID NO: 85; a CDR-H3…SEQ ID NO: 86;….CDR-L1…SEQ ID NO:87, a CDR-L2…SEQ ID NO: 89…and a CDR-L3…SEQ ID NO: 90” recited in instant claim 240 (see the sequence alignment below). Thus, the anti-TNFR2 antibody or antigen-binding fragment thereof disclosed by Thompson anticipates the claimed anti-TNFR2 antibody or antigen-binding fragment thereof recited in instant claim 240 and thus binds to the epitopes recited in claims 243 and 263.
Thompson teaches that the anti-TNFR2 antibody or antigen fragment thereof is an IgG3 or IgG4 isotype as in claims 242 and 262 (see col.14, lines 50-51) or a human IgG1 or IgG2 CH1 domain (see col.14, lines 47-col. 15, line-41), a monoclonal antibody, a humanized antibody, chimeric antibody, a scFv, Fab, F(ab’)2,…as in claims 244 and 264 (see col. 15, lines 30-52; col. 15, line 30-col. 30, line 35; col. 35-38), a single chain polypeptide that can competitively inhibits the binding of human TNFR2 to the single chain polypeptide of the claimed antibody or antigen binding fragment thereof as in claims 245-246 (see col. 13, line 53-col. 30, line 39), and a construct comprises a first polypeptide domain linked to a second polypeptide domain via covalent linker or disulfide bond as in claims 247 and 266-267 (see col.15, lines 25-30). Thompson teaches a pharmaceutical composition or kit comprising the claimed anti-TNFR2 antibody or antigen-binding fragment thereof as in claims 252 and 258 (see col. 9, lines 53-62; col.9, lines 35-40; col. 8, lines 2-14; col.38, line 18-67). Thompson teaches that a pharmaceutical composition optionally comprising an additional therapeutic agent including a chemotherapeutic agent, cytotoxic agent, cytokine, growth-inhibitory agent, anti-hormonal agent, anti-angiogenic agent, and/or cardioprotectant (col.38, lines 57-67). Thus, claims 240, 243-247, 252, 258, 260-264 and 266-267 are anticipated by Thompson. Accordingly, the rejection of claims 240, 243-247, 252, 258, 262-264 and 266-267 under 35 U.S.C. 102(a)(1) as being anticipated by Thompson (US10988543) is maintained.
SEQ ID NO:72/SEQ ID NO:84-SEQ ID NO:85-SEQ ID NO:86
US-15-775-328-7
Sequence 7, US/15775328
Patent No. 10988543
GENERAL INFORMATION
APPLICANT: OPI VI - IP HOLDCO LLC
TITLE OF INVENTION: COMPOSITION AND METHODS FOR ANTI-TNFR2 ANTIBODIES
FILE REFERENCE: 50358-703.601
CURRENT APPLICATION NUMBER: US/15/775,328
CURRENT FILING DATE: 2019-02-06
PRIOR APPLICATION NUMBER: PCT/US2016/061343
PRIOR FILING DATE: 2016-11-10
PRIOR APPLICATION NUMBER: 62/254,127
PRIOR FILING DATE: 2015-11-11
NUMBER OF SEQ ID NOS: 69
SEQ ID NO 7
LENGTH: 119
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
polypeptide
Query Match 97.5%; Score 625; Length 119;
Best Local Similarity 95.8%;
Matches 114; Conservative 5; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLQQSGPEVGKPGASVKISCKASGYTFTDYIMHWVKQSPGQGLEWIGWVDPEYGSTDY 60
||||||||||||:||:||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLQQSGPEVGRPGSSVKISCKASGYTFTDYIMHWVKQSPGQGLEWIGWVDPEYGSTDY 60
Qy 61 AEKFKKRATLTADTSTNTAYIELSSLTSEDTATYFCARDDGSYSPFDYWGQGVMVTVSS 119
||||||:||||||||:|||||:|||||||||||||||||||||||||||||||||||||
Db 61 AEKFKKKATLTADTSSNTAYIQLSSLTSEDTATYFCARDDGSYSPFDYWGQGVMVTVSS 119
SEQ ID NO:78/SEQ ID NO:87-SEQ ID NO:89-SEQ ID NO:90
Sequence 9, US/15775328
Patent No. 10988543
GENERAL INFORMATION
APPLICANT: OPI VI - IP HOLDCO LLC
TITLE OF INVENTION: COMPOSITION AND METHODS FOR ANTI-TNFR2 ANTIBODIES
FILE REFERENCE: 50358-703.601
CURRENT APPLICATION NUMBER: US/15/775,328
CURRENT FILING DATE: 2019-02-06
PRIOR APPLICATION NUMBER: PCT/US2016/061343
PRIOR FILING DATE: 2016-11-10
PRIOR APPLICATION NUMBER: 62/254,127
PRIOR FILING DATE: 2015-11-11
NUMBER OF SEQ ID NOS: 69
SEQ ID NO 9
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
Polypeptide
Query Match 93.6%; Score 526; Length 107;
Best Local Similarity 90.7%;
Matches 97; Conservative 7; Mismatches 3; Indels 0; Gaps 0;
Qy 1 NIVMTQSPSSLSASVGDRVTITCKASENVVTYVSWYQQKPEKAPKLLIYGASNRYTGVPD 60
|||||||| |:| |||:|||:||||||||||||||||||||::|||||||||||||||||
Db 1 NIVMTQSPKSMSMSVGERVTLTCKASENVVTYVSWYQQKPEQSPKLLIYGASNRYTGVPD 60
Qy 61 RFTGSGSATDFTLTISSLQAEDFADYHCGQGYSYPYTFGGGTKVEIK 107
|||||||||||||||||:|||| ||||||||||||||||||||:|||
Db 61 RFTGSGSATDFTLTISSVQAEDLADYHCGQGYSYPYTFGGGTKLEIK 107
New Grounds of Rejection Necessitated by the Amendment
The following rejections are new grounds of rejections necessitated by the amendment filed on February 24, 2026.
Claim Rejections - 35 USC § 112
12. 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 242, 260 and 262 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 pre-AIA the applicant regards as the invention.
Claims 242 and 260 are indefinite because:
i. It is unclear to which position the recited “cysteine residue 127” recited in claims 242 and 260 refers and which sequence is relative to. Thus the claims are indefinite.
ii. claim 262 is indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 103
13. 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 242 and 260-261 are rejected under 35 U.S.C. 103 as being unpatentable over ) in view of Humphreys et al. (US9902768, issued Feb 27, 2018, priority Feb 22, 2012), Le Doussal et al. (US10611848, issued Apr 7, 2020, priority Nov 11, 2013), Neugebauer et al.(US11254734, issued Feb 22, 2022, priority Nov 14, 2016), Presta et al. (US5747035, issued May 5, 1998) and De Kruif et al. (US11952424, issued Apr 9, 2024, priority March 30, 2018).
Thompson is set forth above but fails to teach a human CH1 domain comprising a C127S mutation in claims 242 and 260, or human IgG1 CH1 domain having a sequence at least 85% identical to instant SEQ ID NO: 6 or an amino acid sequence of instant SEQ ID NO:7, a human IgG2 CH1 domain having at least 85% identical to instant SEQ ID NO:8 or having an amino acid sequence of instant SEQ ID NO:9 in claims 260-261.
Humphreys et al. (US9902768) teach a human CH1 domain comprising a C127S mutation for an extended half-life and enhanced ADCC activation or complement activation (see abstract col. 1, lines 45-67, col. 21, lines 36-col. 60; col. 26-col. 28, tables 1-2).
Le Doussal et al. (US10611848) teach a human IgG1 CH1 domain for generation of an antibody, wherein the human IgG1 CH1 domain comprises the amino acid sequence of SEQ ID NO:11, which is 100% identical to instant SEQ ID NO: 6 (see the sequence alignment; col. 6, line 63-col. 7, line 18).
Neugebauer et al. (US11254734) teach a human IgG1 CH1 domain for generation of an antibody for preventing unwanted target receptor activation caused by anti-Fab antibodies present in plasma, wherein the human IgG1 CH1 domain comprises the amino acid sequence of SEQ ID NO:75, which is 100% identical to instant SEQ ID NO: 7 (see the sequence alignment; col. 19-22; col. 25,lines 52-57).
Presta et al. (US5747035) teach a human IgG2 CH1 domain for generation of an antibody with increased half-life, wherein the human IgG2 CH1 domain comprises having the amino acid sequence of SEQ ID NO:5, which is 100% identical to instant SEQ ID NO: 8 (see the sequence alignment).
De Kruif et al. (US11952424) teach a human IgG2 CH1 domain for generation of an antibody, wherein the human IgG2 CH1 domain comprises having the amino acid sequence of SEQ ID NO:272, which is 100% identical to instant SEQ ID NO: 9 (see the sequence alignment).
A person of ordinary skill in the art would have recognized that selecting and applying the known human IgG1 CH1 domain comprising a C127S mutation, or comprising a sequence at least 85% identical to instant SEQ ID NO: 6 or the amino acid sequence of instant SEQ ID NO:7, or the known human IgG2 CH1 domain comprising an amino acid sequence at least 85% identical to instant SEQ ID NO: 8 or the amino acid sequence of instant SEQ ID NO:9 for generation of an antibody with an extended half-life and enhanced ADCC activation or complement activation or preventing unwanted target receptor activation caused by anti-Fab antibodies present in plasma and the known technique disclosed by Humphreys, Le Doussal, Neugebauer, Presta and De Kruif to the Thompson’s anti-TFNR2 antibody would have yielded the predictable result of a anti-TFNR2 antibody with a better therapeutic pharmaceutical composition for different treatment, and resulted in an improved product.
Using and including the known human IgG1 CH1 domain comprising a C127S mutation, or comprising a sequence at least 85% identical to instant SEQ ID NO: 6 or the amino acid sequence of instant SEQ ID NO:7, or the known human IgG2 CH1 domain comprising an amino acid sequence at least 85% identical to instant SEQ ID NO: 8 or the amino acid sequence of instant SEQ ID NO:9 for generation of an antibody with an extended half-life and enhanced ADCC activation or complement activation or preventing unwanted target receptor activation caused by anti-Fab antibodies present in plasma in the Thompson’s anti-TFNR2 antibody would provide better anti-TNFR2 antibody with a better half-life and enhanced ADCC activation or complement activation or preventing unwanted target receptor activation caused by anti-Fab antibodies present in plasma for immunotherapy, and would expand application of the Thompson’s anti-TNFR2 antibody, and increase patient’s satisfaction with treatment using anti-TNFR2 antibody for immunotherapy.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and applythe known human IgG1 CH1 domain comprising a C127S mutation, or comprising a sequence at least 85% identical to instant SEQ ID NO: 6 or the amino acid sequence of instant SEQ ID NO:7, or the known human IgG2 CH1 domain comprising an amino acid sequence at least 85% identical to instant SEQ ID NO: 8 or the amino acid sequence of instant SEQ ID NO:9 for generation of an antibody with an extended half-life and enhanced ADCC activation or complement activation or preventing unwanted target receptor activation caused by anti-Fab antibodies present in plasma and the known technique disclosed by Humphreys, Le Doussal, Neugebauer, Presta and De Kruif to the Thompson’s anti-TFNR2 antibody, and yield the predictable result of a better anti-TFNR2 antibody as a therapeutic agent for immunotherapy.
SEQ ID NO:6
US-15-035-979-11
(NOTE: this sequence has 3 duplicates in the database searched)
Sequence 11, US/15035979
Patent No. 10611848
GENERAL INFORMATION
APPLICANT: ATLAB PHARMA
APPLICANT: UNIVERSITE DE NANTES
APPLICANT: DORVILLIUS, Mylhne
APPLICANT: TERME, Mickakl
APPLICANT: LE DOUSSAL, Jean-Marc
TITLE OF INVENTION: ANTIBODY AGAINST GD2-O-ACETYLATED GANGLIOSIDE WITH PRO-APOPTOTIC
TITLE OF INVENTION: ACTIVITY
FILE REFERENCE: ATL-B-0003-PCT
CURRENT APPLICATION NUMBER: US/15/035,979
CURRENT FILING DATE: 2016-05-11
PRIOR APPLICATION NUMBER: EP 13005298.8
PRIOR FILING DATE: 2013-11-11
NUMBER OF SEQ ID NOS: 34
SEQ ID NO 11
LENGTH: 98
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: mutated human CH1 gamma1
Query Match 100.0%; Score 509; Length 98;
Best Local Similarity 100.0%;
Matches 98; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ASTKGPSVFPLAPCSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ASTKGPSVFPLAPCSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
Qy 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV 98
||||||||||||||||||||||||||||||||||||||
Db 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV 98
SEQ ID NO:7
US-16-348-941-75
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 75, US/16348941
Patent No. 11254734
GENERAL INFORMATION
APPLICANT: MORPHOSYS AG
APPLICANT: Neugebauer, Julia
APPLICANT: Runz, Steffen
APPLICANT: Urlinger, Stefanie
TITLE OF INVENTION: FAB MOLECULES WITH A RODENT HINGE REGION AND A NON-RODENT CH1 REGION
FILE REFERENCE: MOR0064US.NP
CURRENT APPLICATION NUMBER: US/16/348,941
CURRENT FILING DATE: 2019-05-10
PRIOR APPLICATION NUMBER: EP 16198591.6
PRIOR FILING DATE: 2016-11-14
PRIOR APPLICATION NUMBER: PCT/EP2017/078991
PRIOR FILING DATE: 2017-11-13
NUMBER OF SEQ ID NOS: 104
SEQ ID NO 75
LENGTH: 109
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
polypeptide"
Query Match 100.0%; Score 504; Length 109;
Best Local Similarity 100.0%;
Matches 98; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
Qy 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV 98
||||||||||||||||||||||||||||||||||||||
Db 61 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV 98
SEQ ID NO:8
US-08-422-091-5
(NOTE: this sequence has 92 duplicates in the database searched)
Sequence 5, US/08422091
Patent No. 5747035
GENERAL INFORMATION
APPLICANT: Leonard Presta
APPLICANT: Brad Snedecor
TITLE OF INVENTION: Altered Polypeptides with Increased
TITLE OF INVENTION: Half-Life
CURRENT APPLICATION NUMBER: US/08/422,091
CURRENT FILING DATE: 14-APR-1995
NUMBER OF SEQ ID NOS: 31
SEQ ID NO 5
LENGTH: 98
TYPE: PRT
Query Match 100.0%; Score 511; Length 98;
Best Local Similarity 100.0%;
Matches 98; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
Qy 61 GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV 98
||||||||||||||||||||||||||||||||||||||
Db 61 GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV 98
SEQ ID NO:9
US-16-370-346A-272
Sequence 272, US/16370346A
Patent No. 11952424
GENERAL INFORMATION
APPLICANT: Merus N.V.
TITLE OF INVENTION: Multivalent antibody
FILE REFERENCE: P118963PC00
CURRENT APPLICATION NUMBER: US/16/370,346A
CURRENT FILING DATE: 2019-03-29
PRIOR APPLICATION NUMBER: US 62/650,467
PRIOR FILING DATE: 2018-03-30
NUMBER OF SEQ ID NOS: 314
SEQ ID NO 272
LENGTH: 114
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Translation of IgG2BMH
Query Match 100.0%; Score 506; Length 114;
Best Local Similarity 100.0%;
Matches 98; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ASTKGPSVFPLAPSSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ASTKGPSVFPLAPSSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 60
Qy 61 GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV 98
||||||||||||||||||||||||||||||||||||||
Db 61 GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV 98
Claim Rejections - 35 USC § 103
14. Claims 273-274 are rejected under 35 U.S.C. 103 as being unpatentable over ) in view of Faustman (WO2017/040312, published March 9, 2017, priority Aug 28, 2015).
Thompson is set forth above but fails to teach about 0.001-100mg/ml in claim 273 or an agonistic anti-PD-1 agent in claim 273.
Faustman (WO2017/040312) teach that a pharmaceutical composition comprising an agonist anti-TNFR2 antibody in an amount of 0.001-10mg/ml or 0.0001-100mg/kg or 0.0001-500mg/kg or 0.001-100mg/kg daily dose as in claim 273 (p. 23-24; p.71) , and a combination of an agonistic anti-TNFR2 antibody with agonistic anti-PD-1 or anti-PD-L1 antibodies for treatment (see p.65-66; p.70).
A person of ordinary skill in the art would have recognized that selecting and applying the known amount of 0.001-10mg/ml or 0.0001-100mg/kg or 0.0001-500mg/kg or 0.001-100mg/kg daily dose, the known anti-PD-1 or anti-PD-L1 antibody or the known combination of an agonistic anti-TNFR2 antibody with additional immunotherapy agent including anti-PD-1 or anti-PD-L1 antibodies and the known technique disclosed by Faustman to the Thompson’s pharmaceutical composition would have yielded the predictable result of a better therapeutic pharmaceutical composition for different treatment, and resulted in an improved product.
Using and including the known amount of 0.001-10mg/ml or 0.0001-100mg/kg or 0.0001-500mg/kg or 0.001-100mg/kg daily dose for an agonist anti-TNFR2 antibody and the known combination of agonistic anti-TNFR2 antibody with an anti-PD-1 agent in the Thompson’s pharmaceutical composition would provide better immunotherapy effects for immunotherapy, and would expand application of the Thompson’ pharmaceutical composition comprising the claimed anti-TNFR2 antibody, and increase patient’s satisfaction with treatment using anti-TNFR2 antibody and/or anti-PD-1 antibody/agent with other therapeutic agents.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known amount of 0.001-10mg/ml or 0.0001-100mg/kg or 0.0001-500mg/kg or 0.001-100mg/kg daily dose, the known anti-PD-1 or anti-PD-L1 antibody or the known combination of an agonistic anti-TNFR2 antibody with additional immunotherapy agent including anti-PD-1 or anti-PD-L1 antibodies and the known technique disclosed by Faustman to the Thompson’s pharmaceutical composition and yield the predictable result of a better therapeutic agent for immunotherapy.
Conclusion
Allowable Subject Matter
15. Claim 265 is allowable.
16. Claims 241 and 259 are 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.
17. Claims 240, 242-247, 252, 258, 260-264, 266-267 and 273-274 are rejected.
VH
SEQ ID NO:72 1 EVQLQQSGPEVGKPGASVKISCKASGYTFTDYIMHWVKQSPGQGLEWIGWVDPEYGSTDY 60
SEQ ID NO:73 1 EVQLVQSGAEVKKPGASVKISCKASGYTFTDYIMHWVKQAPGQGLEWIGWVDPEYGSTDY 60
SEQ ID NO:74 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYIMHWVRQAPGQGLEWIGWVDPEYGSTDY 60
SEQ ID NO:75 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYIMHWVRQAPGQGLEWIGWVDPEYGSTDY 60
SEQ ID NO:76 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYIMHWVRQAPGQGLEWIGWVDPEYGSTDY 60
SEQ ID NO:77 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYIMHWVRQAPGQGLEWMGWVDPEYGSTDY 60
SEQ ID NO:84 1 ------------------------------DYIMHWV----------------------- 7
SEQ ID NO:85 1 ---------------------------------------------------DPEYGST-- 7
SEQ ID NO:86 ------------------------------------------------------------
SEQ ID NO:72 61 AEKFKKRATLTADTSTNTAYIELSSLTSEDTATYFCARDDGSYSPFDYWGQGVMVTVSS 119
SEQ ID NO:73 61 AEKFKKRATLTADTSTNTAYIELSSLTSEDTATYFCARDDGSYSPFDYWGQGVLVTVSS 119
SEQ ID NO:74 61 AEKFKKRATLTADTSTNTAYIELSSLTSEDTATYFCARDDGSYSPFDYWGQGTLVTVSS 119
SEQ ID NO:75 61 AEKFKKRVTMTADTSTNTAYMELSSLTSEDTATYFCARDDGSYSPFDYWGQGTLVTVSS 119
SEQ ID NO:76 61 AEKFKKRVTMTADTSTNTAYMELSSLRSEDTAVYYCARDDGSYSPFDYWGQGTLVTVSS 119
SEQ ID NO:77 61 AEKFKKRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDGSYSPFDYWGQGTLVTVSS 119
SEQ ID NO:84 ------------------------------------------------------------
SEQ ID NO:85 ------------------------------------------------------------
SEQ ID NO:86 1 --------------------------------------DDGSYSPFD------------- 9
VL
SEQ ID NO:78 1 NIVMTQSPSSLSASVGDRVTITCKASENVVTYVSWYQQKPEKAPKLLIYGASNRYTGVPD 60
SEQ ID NO:79 1 NIVMTQSPSSLSASVGDRVTITCKASENVVTYVSWYQQKPGKAPKLLIYGASNRYTGVPD 60
SEQ ID NO:80 1 DIQMTQSPSSLSASVGDRVTITCKASENVVTYVSWYQQKPGKAPKLLIYGASNRYTGVPD 60
SEQ ID NO:81 1 DIQMTQSPSSLSASVGDRVTITCRASENVVTYVSWYQQKPGKAPKLLIYGASNRYTGVPD 60
SEQ ID NO:82 1 DIQMTQSPSSLSASVGDRVTITCKASENVVTYVSWYQQKPGKAPKLLIYGASNRYTGVPD 60
SEQ ID NO:83 1 DIQMTQSPSSLSASVGDRVTITCKASENVVTYVSWYQQKPGKAPKLLIYGASNRYTGVPS 60
SEQ ID NO:87 1 -----------------------KASENVVTYVS-------------------------- 11
SEQ ID NO:88 1 -----------------------RASENVVTYVS-------------------------- 11
SEQ ID NO:89 1 -------------------------------------------------GASNRYT---- 7
SEQ ID NO:78 61 RFTGSGSATDFTLTISSLQAEDFADYHCGQGYSYPYTFGGGTKVEIK 107
SEQ ID NO:79 61 RFTGSGSATDFTLTISSLQPEDFADYHCGQGYSYPYTFGGGTKVEIK 107
SEQ ID NO:80 61 RFSGSGSATDFTLTISSLQPEDFADYHCGQGYSYPYTFGGGTKVEIK 107
SEQ ID NO:81 61 RFSGSGSATDFTLTISSLQPEDFADYHCGQGYSYPYTFGGGTKVEIK 107
SEQ ID NO:82 61 RFSGSGSATDFTLTISSLQPEDFATYHCGQGYSYPYTFGGGTKVEIK 107
SEQ ID NO:83 61 RFSGSGSGTDFTLTISSLQPEDFATYYCGQGYSYPYTFGGGTKVEIK 107
SEQ ID NO:87 -----------------------------------------------
SEQ ID NO:88 -----------------------------------------------
SEQ ID NO:89 -----------------------------------------------
SEQ ID NO:90 1 ----------------------------GQGYSYPY----------- 8
18. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
WO2025117965 teaches an anti-TNFR2 antibody having a VH comprising SEQ ID NO:683, which is 100% identical to instant SEQ ID NO:72, and a VL comprising SEQ ID NO:684, which is 100% identical to instant SEQ ID NO:78 (see the sequence alignment below).
SEQ ID NO:72
ID BRL47453 standard; protein; 119 AA.
XX
AC BRL47453;
XX
DT 24-JUL-2025 (first entry)
XX
DE Anti-TNFR2 antibody heavy chain variable region, SEQ 683.
XX
KW TNFR2 protein; Tumor necrosis factor receptor 2; allergy; antiallergic;
KW antibody; antibody engineering; antibody production; antibody therapy;
KW antiinflammatory; antimicrobial-gen.; autoimmune disease; cytostatic;
KW graft versus host disease; heavy chain variable region;
KW immune modulation; immunosuppressive; infectious disease;
KW inflammatory disease; neoplasm; neurological disease; neuroprotective;
KW therapeutic; tissue regeneration; transplant rejection; transplantation.
XX
OS Unidentified.
XX
CC PN WO2025117965-A1.
XX
CC PD 05-JUN-2025.
XX
CC PF 02-DEC-2024; 2024WO-US058117.
XX
PR 01-DEC-2023; 2023US-0605306P.
PR 17-JUL-2024; 2024US-0672340P.
PR 28-AUG-2024; 2024US-00818268.
PR 28-AUG-2024; 2024US-0688121P.
XX
CC PA (GEHO ) GEN HOSPITAL CORP.
XX
CC PI Faustman DL;
XX
DR WPI; 2025-58833A/051.
XX
CC PT Treating autoimmune disease comprises contacting Th17 cell or Th17 cells
CC PT with an exogenous T cell modulating agent to decrease expression of pro-
CC PT inflammatory Th17 transcription factor and/or increase expression of
CC PT antiinflammatory Th17.
XX
CC PS Claim 14; SEQ ID NO 683; 272pp; English.
XX
CC The present invention relates to a novel method for modulating an immune
CC response in a human subject. The method comprises administering to the
CC subject a modified antibody or its antigen-binding fragment that
CC specifically binds a human tumor necrosis factor receptor superfamily
CC (TNFRSF) member protein, where the modified antibody or its antigen-
CC binding fragment comprises an Fc domain with one or more amino acid
CC modifications, and where the modified antibody or its antigen-binding
CC fragment is administered to the human subject at a higher dose and/or
CC frequency relative to an unmodified antibody or its antigen-binding
CC fragment. The invention further provides: (1) an antibody or its antigen-
CC binding fragment that specifically binds a human TNFRSF member protein,
CC where the antibody or its antigen-binding fragment thereof comprises at
CC least 50 amino acid residues of an Fc domain and one or more amino acid
CC substitutions within the Fc domain; (2) an agonistic antibody or its
CC antigen-binding fragment that specifically binds human TNFR2; (3) an
CC antibody or its antigen-binding fragment that specifically binds a human
CC TNFSF member protein; (4) an antibody or its antigen-binding fragment
CC that specifically binds human CD28; (5) an antibody or its antigen-
CC binding fragment that specifically binds human ICOS; (6) a method for
CC producing the antibody or antigen-binding fragment; (7) a construct
CC comprising a first polypeptide domain and a second polypeptide domain,
CC where the first polypeptide domain and the second polypeptide domain are
CC each, independently, an antigen-binding fragment; (8) a polynucleotide
CC encoding the antibody or its antigen-binding fragment or the construct;
CC (9) a vector comprising the polynucleotide; (10) an isolated host cell
CC comprising the vector; (11) a pharmaceutical composition comprising the
CC antibody or its antigen-binding fragment, the construct, the
CC polynucleotide, the vector, or the host cell, and a pharmaceutically
CC acceptable carrier or excipient; (12) a kit comprising an agent selected
CC from the group consisting of the antibody or its antigen-binding
CC fragment, the construct, the polynucleotide, the vector, or the host
CC cell, or the pharmaceutical composition; and (13) a modified antibody or
CC its antigen-binding fragment that specifically binds TNFR2, where the
CC modified antibody or its antigen-binding fragment comprises a heavy chain
CC variable region, a light chain variable region, and a modified human IgG4
CC constant region comprising a modified human IgG4 Fc hinge region, where
CC the modified human IgG4 constant region comprises an amino acid sequence
CC having at least 95 percentage identity to the amino acid sequence of SEQ
CC ID NO: 1547 (see BRL48308), where the modified human IgG4 Fc hinge region
CC comprises the amino acid substitution of S228P, and where the amino acid
CC position is numbered according to the EU index. The method of the
CC invention is useful for treating a cell proliferation disorder, an
CC autoimmune disease, an infectious disease, an inflammatory disease, a
CC neurological disease, an allergy, a transplant rejection, or a graft-
CC versus-host disease in the human subject, and for transplantation or for
CC regenerating a tissue or organ in the human subject.
XX
SQ Sequence 119 AA;
Query Match 100.0%; Score 641; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLQQSGPEVGKPGASVKISCKASGYTFTDYIMHWVKQSPGQGLEWIGWVDPEYGSTDY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLQQSGPEVGKPGASVKISCKASGYTFTDYIMHWVKQSPGQGLEWIGWVDPEYGSTDY 60
Qy 61 AEKFKKRATLTADTSTNTAYIELSSLTSEDTATYFCARDDGSYSPFDYWGQGVMVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AEKFKKRATLTADTSTNTAYIELSSLTSEDTATYFCARDDGSYSPFDYWGQGVMVTVSS 119
SEQ ID NO:78
ID BRL47454 standard; protein; 107 AA.
XX
AC BRL47454;
XX
DT 24-JUL-2025 (first entry)
XX
DE Anti-TNFR2 antibody light chain variable region, SEQ 684.
XX
KW TNFR2 protein; Tumor necrosis factor receptor 2; allergy; antiallergic;
KW antibody; antibody engineering; antibody production; antibody therapy;
KW antiinflammatory; antimicrobial-gen.; autoimmune disease; cytostatic;
KW graft versus host disease; immune modulation; immunosuppressive;
KW infectious disease; inflammatory disease; light chain variable region;
KW neoplasm; neurological disease; neuroprotective; therapeutic;
KW tissue regeneration; transplant rejection; transplantation.
XX
OS Unidentified.
XX
CC PN WO2025117965-A1.
XX
CC PD 05-JUN-2025.
XX
CC PF 02-DEC-2024; 2024WO-US058117.
XX
PR 01-DEC-2023; 2023US-0605306P.
PR 17-JUL-2024; 2024US-0672340P.
PR 28-AUG-2024; 2024US-00818268.
PR 28-AUG-2024; 2024US-0688121P.
XX
CC PA (GEHO ) GEN HOSPITAL CORP.
XX
CC PI Faustman DL;
XX
DR WPI; 2025-58833A/051.
XX
CC PT Treating autoimmune disease comprises contacting Th17 cell or Th17 cells
CC PT with an exogenous T cell modulating agent to decrease expression of pro-
CC PT inflammatory Th17 transcription factor and/or increase expression of
CC PT antiinflammatory Th17.
XX
CC PS Claim 14; SEQ ID NO 684; 272pp; English.
XX
CC The present invention relates to a novel method for modulating an immune
CC response in a human subject. The method comprises administering to the
CC subject a modified antibody or its antigen-binding fragment that
CC specifically binds a human tumor necrosis factor receptor superfamily
CC (TNFRSF) member protein, where the modified antibody or its antigen-
CC binding fragment comprises an Fc domain with one or more amino acid
CC modifications, and where the modified antibody or its antigen-binding
CC fragment is administered to the human subject at a higher dose and/or
CC frequency relative to an unmodified antibody or its antigen-binding
CC fragment. The invention further provides: (1) an antibody or its antigen-
CC binding fragment that specifically binds a human TNFRSF member protein,
CC where the antibody or its antigen-binding fragment thereof comprises at
CC least 50 amino acid residues of an Fc domain and one or more amino acid
CC substitutions within the Fc domain; (2) an agonistic antibody or its
CC antigen-binding fragment that specifically binds human TNFR2; (3) an
CC antibody or its antigen-binding fragment that specifically binds a human
CC TNFSF member protein; (4) an antibody or its antigen-binding fragment
CC that specifically binds human CD28; (5) an antibody or its antigen-
CC binding fragment that specifically binds human ICOS; (6) a method for
CC producing the antibody or antigen-binding fragment; (7) a construct
CC comprising a first polypeptide domain and a second polypeptide domain,
CC where the first polypeptide domain and the second polypeptide domain are
CC each, independently, an antigen-binding fragment; (8) a polynucleotide
CC encoding the antibody or its antigen-binding fragment or the construct;
CC (9) a vector comprising the polynucleotide; (10) an isolated host cell
CC comprising the vector; (11) a pharmaceutical composition comprising the
CC antibody or its antigen-binding fragment, the construct, the
CC polynucleotide, the vector, or the host cell, and a pharmaceutically
CC acceptable carrier or excipient; (12) a kit comprising an agent selected
CC from the group consisting of the antibody or its antigen-binding
CC fragment, the construct, the polynucleotide, the vector, or the host
CC cell, or the pharmaceutical composition; and (13) a modified antibody or
CC its antigen-binding fragment that specifically binds TNFR2, where the
CC modified antibody or its antigen-binding fragment comprises a heavy chain
CC variable region, a light chain variable region, and a modified human IgG4
CC constant region comprising a modified human IgG4 Fc hinge region, where
CC the modified human IgG4 constant region comprises an amino acid sequence
CC having at least 95 percentage identity to the amino acid sequence of SEQ
CC ID NO: 1547 (see BRL48308), where the modified human IgG4 Fc hinge region
CC comprises the amino acid substitution of S228P, and where the amino acid
CC position is numbered according to the EU index. The method of the
CC invention is useful for treating a cell proliferation disorder, an
CC autoimmune disease, an infectious disease, an inflammatory disease, a
CC neurological disease, an allergy, a transplant rejection, or a graft-
CC versus-host disease in the human subject, and for transplantation or for
CC regenerating a tissue or organ in the human subject.
XX
SQ Sequence 107 AA;
Query Match 100.0%; Score 562; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NIVMTQSPSSLSASVGDRVTITCKASENVVTYVSWYQQKPEKAPKLLIYGASNRYTGVPD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 NIVMTQSPSSLSASVGDRVTITCKASENVVTYVSWYQQKPEKAPKLLIYGASNRYTGVPD 60
Qy 61 RFTGSGSATDFTLTISSLQAEDFADYHCGQGYSYPYTFGGGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFTGSGSATDFTLTISSLQAEDFADYHCGQGYSYPYTFGGGTKVEIK 107
US20250179203 teaches an anti-TNFR2 antibody having a VH comprising SEQ ID NO:683, which is 100% identical to instant SEQ ID NO:72, and a VL comprising SEQ ID NO:684, which is 100% identical to instant SEQ ID NO:78 (see the sequence alignment below).
SEQ ID NO:72
Sequence 683, US/18818268
Publication No. US20250179203A1
GENERAL INFORMATION
APPLICANT: The General Hospital Corporation (en)
TITLE OF INVENTION: ANTIBODIES WITH FC MODIFICATIONS AND METHODS OF USING THE SAME (en)
FILE REFERENCE: 00786-592004
CURRENT APPLICATION NUMBER: US/18/818,268
CURRENT FILING DATE: 2024-08-28
NUMBER OF SEQ ID NOS: 1547
SEQ ID NO 683
LENGTH: 119
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..119
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 100.0%; Score 641; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLQQSGPEVGKPGASVKISCKASGYTFTDYIMHWVKQSPGQGLEWIGWVDPEYGSTDY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLQQSGPEVGKPGASVKISCKASGYTFTDYIMHWVKQSPGQGLEWIGWVDPEYGSTDY 60
Qy 61 AEKFKKRATLTADTSTNTAYIELSSLTSEDTATYFCARDDGSYSPFDYWGQGVMVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AEKFKKRATLTADTSTNTAYIELSSLTSEDTATYFCARDDGSYSPFDYWGQGVMVTVSS 119
SEQ ID NO:78
Sequence 684, US/18818268
Publication No. US20250179203A1
GENERAL INFORMATION
APPLICANT: The General Hospital Corporation (en)
TITLE OF INVENTION: ANTIBODIES WITH FC MODIFICATIONS AND METHODS OF USING THE SAME (en)
FILE REFERENCE: 00786-592004
CURRENT APPLICATION NUMBER: US/18/818,268
CURRENT FILING DATE: 2024-08-28
NUMBER OF SEQ ID NOS: 1547
SEQ ID NO 684
LENGTH: 107
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..107
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 100.0%; Score 562; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 NIVMTQSPSSLSASVGDRVTITCKASENVVTYVSWYQQKPEKAPKLLIYGASNRYTGVPD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 NIVMTQSPSSLSASVGDRVTITCKASENVVTYVSWYQQKPEKAPKLLIYGASNRYTGVPD 60
Qy 61 RFTGSGSATDFTLTISSLQAEDFADYHCGQGYSYPYTFGGGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFTGSGSATDFTLTISSLQAEDFADYHCGQGYSYPYTFGGGTKVEIK 107
19. 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.
20. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Chang-Yu Wang
April 2, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675