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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant's submission filed on 06/02/2026 has been entered.
Status of the Claims
Claims 1, 17 – 23, 27 – 28 and 32 were pending. Claims 1, 17 – 23, 27 – 28 and 32 have been canceled, and claims 34 – 53 have been newly added. Claims 34 – 53 are currently pending and are the subject of this Office Action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/02/2026 is in compliance with the provisions of 37 CFR 1.97 and has been considered.
Claim Rejections - 35 USC § 112
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.
Claims 44 – 45 are 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 43, from with claims 44 – 45 ultimately depend, claims a bispecific polypeptide comprising SEQ ID NO: 92. However, claims 44 and 45 recite mutations in SEQ ID NO: 92 which is broader in scope than SEQ ID NO: 92. Thus, claims 44 – 45 fail to further limit claim 43.
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.
Allowable Subject Matter
Claim 43 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The sequences of SEQ ID NOs: 89, 91, and 92 are disclosed by the prior art with 100% identity. KEYT (WO 2015/153912 A1, published 10/08/2015; see PTO-892 of 11/06/2024) is directed to modified recombinant J-chain polypeptides, binding molecules, such as antibodies comprising the same, and their uses. See abstract. KEYT teaches that the polypeptides may be used in the treatment of cancer, such as lymphoma (see claims 48 and 51) and teaches the molecular cloning, expression and purification of a bispecific anti-CD20 IgM antibody with a modified J-chain carrying an anti-CD3 binding scFv (see Example 2). KEYT’s SEQ ID NO: 48 discloses present SEQ ID NO: 91 with 100% identity. See Appendix of record.
LIU discloses SEQ ID NOs: 89 and 92 with 100% identity. See Appendix of record.
However, the prior art does not teach the sequence of SEQ ID NO: 90 with 100% identity. Because SEQ ID NO: 90 is required for its structure, a bispecific polypeptide complex comprising five polypeptide chains: SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ IDNO: 91, and SEQ IDNO: 92 is free of the art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 34 – 42 and 45 – 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 20 of U.S. Patent No. 11,365,254 in view of SHENZHEN (CN107501412A, published 12/22/2017; see PTO-892: Notice of References Cited of 11/06/2024).
Patented claim 1 recites a bispecific polypeptide complex, comprising a first antigen-binding moiety associated with a second antigen-binding moiety, wherein: the first antigen-binding moiety comprises: a first polypeptide comprising, from N-terminus to C-terminus, a first heavy chain variable domain (VH) of a first antibody operably linked to a first T cell receptor (TCR) constant region (C1), and
a second polypeptide comprising, from N-terminus to C-terminus, a first light chain variable domain (VL) of the first antibody operably linked to a second TCR constant region (C2), wherein: C1 comprises an engineered CBeta comprising SEQ ID NO: 1 and C2 comprises an engineered CAlpha comprising SEQ ID NO: 2, amino acid C48 in SEQ ID NO: 1 and amino acid C41 in SEQ ID NO: 2 are capable of forming a non-native interchain disulphide bond, C1 and C2 are capable of forming a dimer, and the non-native interchain disulphide bond is capable of stabilizing the dimer, and the second antigen-binding moiety comprises: a second VH of a second antibody operably linked to an antibody heavy chain CH1 domain, and a second VL of the second antibody operably linked to an antibody light chain constant (CL) domain,
wherein: one of the first and the second antigen-binding moiety is an anti-CD3 binding moiety, and the other one is an anti-CD19 binding moiety, the anti-CD3 binding moiety is derived from an anti-CD3 antibody comprising: a) a heavy chain CDR1 comprising SEQ ID NO: 3, b) a heavy chain CDR2 comprising SEQ ID NO: 4, c) a heavy chain CDR3 comprising SEQ ID NO: 5, d) a kappa light chain CDR1 comprising SEQ ID NO: 6, e) a kappa light chain CDR2 comprising SEQ ID NO: 7, and f) a kappa light chain CDR3 comprising SEQ ID NO: 8; the anti-CD19 binding moiety is derived from an anti-CD19 antibody comprising: a) a heavy chain CDR1 comprising SEQ ID NO: 9, b) a heavy chain CDR2 comprising SEQ ID NO: 10, c) a heavy chain CDR3 comprising SEQ ID NO: 11, d) a kappa light chain CDR1 comprising SEQ ID NO: 12, e) a kappa light chain CDR2 comprising SEQ ID NO: 13, and f) a kappa light chain CDR3 comprising SEQ ID NO: 14, and the first antigen-binding moiety and the second antigen-binding moiety are less prone to mispair than otherwise would have been if both the first and the second antigen-binding moieties are counterparts of natural Fab.
Patented claim 2 recites that the anti-CD3 binding moiety comprises a heavy chain variable domain sequence comprising SEQ ID NO: 15 and a light chain variable domain sequence comprising SEQ ID NO: 17.
Patented claim 11 recites that the bispecific polypeptide complex comprises a combination of four polypeptide sequences: SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, and SEQ ID NO: 29.
The patented claims’ SEQ ID NO: 15 discloses the CDRs of SEQ ID NOs: 25 – 27 and 65 with 100% identity, and the patented claims’ SEQ ID NO: 17 or 26 discloses the CDRs of present SEQ ID NOs: 28 – 30 and 66 with 100% identity. Patented SEQ ID NO: 26 also discloses the sequence of present SEQ ID NO: 122 with 100% identity. The patented claims’ SEQ ID NO: 27 discloses present SEQ ID NO: 121 with 100% identity; and the patented claims’ SEQ ID NO: 26 discloses present SEQ ID NO: 122 with 100% identity. See Appendix of record.
The main difference between the present claims and the patented claims is that the present claims recite that one of the first and the second antigen-binding moiety is an anti-CD3 binding moiety and the other is an anti-CD20 binding moiety instead of the other being the anti-CD19 binding moiety of the patented claims. However, SHENZHEN teaches this difference.
SHENZHEN is directed to an anti-CD20/CD3 bispecific antibody that may be used to treat tumors. See abstract and claim 10. SHENZHEN’s SEQ ID NO: 2 discloses present SEQ ID NOs: 31 – 33 with 100% identity, and SHENZHEN’s SEQ ID NO: 1 discloses present SEQ ID NOs: 34 – 36 with 100% identity. See Appendix of record.
Because the patented claims recite a bispecific polypeptide complex having the same general structure as that of the present claims, including the anti-CD3 binding moiety, and SHENZHEN teaches the anti-CD20 binding moiety, it would have been obvious to one having ordinary skill in the art to use the patented claims’ bispecific polypeptide with SHENZHEN’s anti-CD20 binding moiety because SHENZHEN teaches an anti-CD20/anti-CD3 bispecific antibody that is easy to produce and which easily penetrates into tumor tissues (see English translation of SHENZHEN, p. 2, last paragraph under “Background technology”). Thus, there would have been a reasonable expectation of success given that a bispecific polypeptide complex with the structure of present claim 34 and with anti-CD3 and anti-CD20 binding moieties has been known to successfully treat cancer as evidenced by the applied prior art.
Claims 34 – 42 and 45 – 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 40, 48, 53, 55, 57 – 59, 69 – 70 and 91 of U.S. Application No. 18/480,252 in view of SHENZHEN.
Copending claim 40 recites a bispecific polypeptide complex, comprising a first antigen-binding moiety associated with a second antigen-binding moiety, wherein: the first antigen-binding moiety comprises: a first polypeptide comprising, from N-terminus to C-terminus, a first heavy chain variable domain (VH) of a first antibody operably linked to a first T cell receptor (TCR) constant region (C1), and a second polypeptide comprising, from N-terminus to C-terminus, a first light chain variable domain (VL) of the first antibody operably linked to a second TCR constant region (C2), wherein: C1 and C2 are capable of forming a dimer comprising at least one non-native interchain bond between a first mutated residue comprised in C1 and a second mutated residue comprised in C2, and the non-native interchain bond is capable of stabilizing the dimer, and the first antibody has a first antigenic specificity, the second antigen-binding moiety has a second antigenic specificity which is different from the first antigenic specificity, and the first antigen-binding moiety and the second antigen-binding moiety are less prone to mispair than otherwise would have been if both the first and the second antigen-binding moieties are counterparts of a natural Fab.
Copending claim 57 recites that the chimeric constant region and C2 comprises a pair of sequences selected from the group consisting of: SEQ ID NOs: 177/176, 179/178, 184/183, 185/183, 180/176, 181/178, 182/178, 184/186, 185/186, 188/187, 196/187, 190/189, 192/191, 192/193, 195/194, 198/197, 200/199, 202/201, 203/201, 203/204, 205/204, 206/204, 208/207, 208/209, 211/210, 213/212, 213/151, 214/212, 214/151, 234/233, 232/231, 216/215, 218/217, 220/219, 222/221, 224/223, 226/225, 227/223, 229/228, 229/230, 236/235 and 238/237.
Copending claim 58 recites that the first antigenicity is directed to CD3, and the first polypeptide and the second polypeptide comprise a pair of sequences selected from the group consisting of: SEQ ID NOs: 2/1, 4/3, 5/1, 6/3, 7/3, 9/8, 10/8, 9/11, 10/11, 13/12, 15/14, 17/16, 17/18, 20/19, 21/12, 65/64, 67/66, 69/68, 70/68, 70/71, 72/71, 73/71, 75/74, 75/76, 78/77, 86/85, 90/89, 91/92, 94/93, 96/95, 98/97, 99/95, 101/100, 101/102, 106/105, 108/107, 110/109, 112/111, 137/136, 138/136, 137/139 and 138/139.
Copending claim 57’s SEQ ID NOs: 188/187, 196/187, 192/191, 192/193, 195/194 pairs each teach the pair of present SEQ ID NOs: 121/122 of present claim 34 with 100% identity.
Copending SEQ ID NOs: 2/1, 4/3, 5/1, 6/3, 7/3, 9/8, 10/8, 9/11, 10/11, 13/12, 15/14, 17/16, 17/18, 20/19, 21/12, 65/64, 67/66, 69/68, 70/68, 70/71, 72/71, 73/71, 75/74, 75/76, 78/77, 86/85, 90/89, 91/92, 94/93, 96/95, 98/97, 99/95, 101/100, 101/102, 106/105, 108/107, 110/109, 112/111, 137/136, 138/136, 137/139 and 138/139 teach the anti-CD3 CDRs of present claim 34.
The main difference between the present claims and the copending claims is that the present claims recite that one of the first and the second antigen-binding moiety is an anti-CD3 binding moiety and the other is an anti-CD20 binding moiety instead of the other being theanti-CD19 binding moiety of the copending claims. However, SHENZHEN teaches this difference.
Regarding the anti-CD20 CDRs of SEQ ID NOs: 31 – 36 of present claim 1, SHENZHEN discloses the sequences with 100% identity. SHENZHEN’s SEQ ID NO: 2 discloses present SEQ ID NOs: 31 – 33 and 75, and SHENZHEN’s SEQ ID NO: 1 discloses present SEQ ID NOs: 34 – 36 and 76. See Appendix of record.
Because the copending claims recite a bispecific polypeptide complex having the same general structure as that of the present claims, including the anti-CD3 binding moiety, and SHENZHEN teaches the anti-CD20 binding moiety, it would have been obvious to one having ordinary skill in the art to use the copending claims’ bispecific polypeptide with the anti-CD20 binding moiety of SHENZHEN because SHENZHEN teaches an anti-CD20/anti-CD3 bispecific antibody that is easy to produce and which easily penetrates into tumor tissues (see English translation of SHENZHEN, p. 2, last paragraph under “Background technology”). There would have been a reasonable expectation of success given that a bispecific polypeptide complex with the structure of present claim 34 and with anti-CD3 and anti-CD20 binding moieties has been known to successfully treat cancer as evidenced by the applied prior art.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 34 – 42 and 44– 53 are rejected, and claim 43 is objected to.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/PETER J REDDIG/Primary Examiner, Art Unit 1646
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