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 final rejection. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/06/2026 has been entered.
Status of the Claims
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54 – 55, 60, 119, 121, 123, 133, and 140 – 147 were pending and are the subject of this Office Action. Claims 1, 6, 22, 25 – 26, 33 – 34, 36 – 37, 54 – 55, 60, 119, 121, 123, 133 have been amended, and claim 3 has been canceled. Claims 1, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54 – 55, 60, 119, 121, 123, 133 and 140 – 147 are currently pending and are the subject of this Office Action.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 02/04/2026, 03/06/2026 and 06/25/2026 are in compliance with the provisions of 37 CFR 1.97 and have been considered.
REJECTIONS WITHDRAWN
Claim Rejections - 35 USC § 112
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54 – 55, 60, 119, 121, 123, and 140 – 147are 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.
In view of amendment to claim 1 in the reply of 03/06/2026, this rejection is withdrawn.
NEW REJECTION
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 6, 13, 22, 25, 54 – 55, 119, 121, 133, 140 – 141, and 143 – 145 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by BEREZHNOY (WO 2021/167885 A1, published 08/26/2021; see PTO-892: Notice of References Cited of 04/30/2025).
Independent claim 1 recites a method for reducing progression of a tumor or treating cancer in a subject in need thereof, the method comprising administering to the subject a combination therapy, wherein the combination therapy consists of (i) multispecific binding agent and (ii) a PD-1 antibody, wherein the multispecific binding agent is administered prior to, simultaneously with, or after administration of the PD-1 antibody, wherein the multispecific binding agent comprises a first binding arm capable of binding to CD137, wherein the first binding arm comprises a first heavy chain variable region (VH) comprising the HCDR1, HCDR2, and HCDR3 sequences as set forth in SEQ ID NOs: 2, 3, and 4, respectively, and a first light chain variable region (VL) comprising the LCDR1, LCDR2, and LCDR3 sequences as set forth in SEQ ID NOs: 6, GAS, and 8, respectively, and wherein the multispecific binding agent comprises a second binding arm capable of binding to PD-L1, wherein the second binding arm comprises a second VH comprising the HCDR1, HCDR2, and HCDR3 sequences set forth in SEQ ID NOs: 12, 13, and 14, respectively, and wherein the second binding arm comprises a second VL comprising the LCDR1, LCDR2, LCDR3 sequences set forth in SEQ ID NOs: 16, DDN, and 18, respectively; and wherein the PD-1 antibody is not an antibody comprising a heavy chain variable region (VH) comprising the CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NO: 59, 60 and 61, respectively, and a light chain variable region (VL) comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 62, 63, and 64, respectively, or an antigen-binding fragment thereof.
Because the PD-1 inhibitor is limited to nivolumab in claim 6, nivolumab is understood have the property of “not an antibody comprising a heavy chain variable region (VH) comprising the CDR1, CDR2 and CDR3 sequences set forth in SEQ ID NO: 59, 60 and 61, respectively, and a light chain variable region (VL) comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 62, 63, and 64, respectively, or an antigen-binding fragment thereof” of claims 1 and 133.
BEREZHNOY is directed to multispecific CD137 Binding Molecules (e.g., bispecific antibodies, bispecific diabodies, BiTEs, trivalent binding molecules, etc.) that are capable of binding to both an epitope of CD137 and to an epitope of a second antigen and novel PD-L1 Binding Molecules, such as monospecific antibodies, and molecules for the treatment of disease, especially cancer. See paragraph 003. BEREZHNOY discloses that the CD137 x PD-L1 Binding Molecules of the present invention may additionally be used in combination with a PD-1 checkpoint inhibitor such as the antibody nivolumab. See paragraph 00447. Furthermore, BEREZHNOY discloses the anti-CD137 CDRs and anti-PD-L1 CDRs of present claims 1 and 133. Thus, BEREZHNOY teaches the methods of claims 1 and 6.
Regarding claims 1 and 133, BEREZHNOY’s SEQ ID NO: 157 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2, 3, and 4 with 100% identity. BEREZHNOY’s SEQ ID NO: 158 discloses the anti-CD137 CDRs of present SEQ ID NO: 6, sequence GAS, and SEQ ID NO: 8 with 100% identity. See Appendix of record.
BEREZHNOY’s SEQ ID NO: 159 discloses the anti-PD-1 CDRs of present SEQ ID NOs: 12, 13, and 14 with 100% identity, and BEREZHNOY’s SEQ ID NO: 160 discloses the anti-PD-1 CDRs of present SEQ ID NO: 16, sequence DDN, and SEQ ID NO: 18 of present claims 1 and 133 with 100% identity. See Appendix of record.
Regarding claim 13, BEREZHNOY discloses the sequences of SEQ ID NOs: 1, 5, 11, and 15. BEREZHNOY’s SEQ ID NO: 157 discloses present SEQ ID NO: 1 with 100% identity, and BEREZHNOY’s SEQ ID NO: 158 is discloses present SEQ ID NO: 5 with 100% identity. BEREZHNOY’s SEQ ID NO: 159 discloses present SEQ ID NO: 11 with 100% identity, and BEREZHNOY’s SEQ ID NO: 160 discloses present SEQ ID NO: 15 with 100% identity. See Appendix of record.
Regarding claim 22, BEREZHNOY discloses a heavy chain constant region and a light chain constant region. See paragraphs 0135-0143 and 0143, Table on p. 151 and SEQ ID NOs: 157 and 159.
Regarding claim 25, BEREZHNOY discloses an IgG1 Fc domain having a modification at T366, L368, or Y407. See paragraph 0143.
Regarding claim 54, BEREZHNOY discloses the sequences of SEQ ID NOs: 31 – 34. Each of BEREZHNOY’s SEQ ID NOs: 157 – 160 is identical to present SEQ ID NOs: 31 – 34, respectively. See Appendix of record.
Regarding claim 55, according to the present specification, acasunlimab has the CDRs of present claim 1 and the VHs and VLs of present claim 13 (“Items of the present disclosure” #s 1, 7 – 13 and 55, p. 106 – 109 and 116 of the present specification). Because BEREZHNOY’s multispecific CD137 Binding Molecule teaches the CDRs of present claim 1 and the VHs and VLs of present claim 13 as discussed above, BEREZHNOY’s multispecific CD137 Binding Molecule is acasunlimab.
Regarding claims 119 and 121, BEREZHNOY discloses that the pharmaceutical compositions can be administered once a week, twice a week, once every two weeks, once a month, once every six weeks, once every two months, twice a year or once per year. See paragraph 00441. BEREZHNOY also discloses that an "effective amount" may be considered in the context of administering one or more additional agents (e.g., chemotherapeutic agents, or other agents considered standard of care for the particular condition), and a single agent may be considered to be given in an effective amount. See paragraph 00437.
Regarding claim 133, BEREZHNOY discloses a pharmaceutical pack or kit comprising one or more containers containing a CD137 x TA Binding Molecule of the present invention alone or with other agents. See paragraphs 00429 – 00430.
Regarding claims 140 and 141, BEREZHNOY teaches that the disclosed method may be used to treat lung cancer, melanoma, neuroblastoma, non-small cell lung cancer (NSCLC). See paragraph 0045, p. 11.
Regarding claim 143, BEREZHNOY teaches decreasing symptoms resulting from the disease attenuating a symptom of disease (e.g., the proliferation of cancer cells, tumor presence, tumor metastases, etc.). See paragraph 00436, p. 111.
Regarding claims 144 and 145, BEREZHNOY teaches that “one or more of the molecules may be administered “sequentially” (e.g., a CD137 x TA Binding Molecule is administered and, at a later time, a TA x CD3 Binding Molecule and/or a PD-1/PD-L1 Checkpoint Inhibitor is administered” (see paragraph 00448, p. 115), suggesting a scenario where the subject has not received prior treatment with a checkpoint inhibitor.
MAINTAINED REJECTIONS IN MODIFIED FORM
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 142 and 146 – 147 are rejected under 35 U.S.C. 103 as being unpatentable over BEREZHNOY as applied to claims 1, 6, 13, 22, 25, 54 – 55, 119, 121, 133, 140 – 141, and 143 – 145 above, and further in view of CAMPBELL (US 2020/0190191 A1, published 06/18/2020; see PTO 892 of 09/08/2025).
The teachings of BEREZHNOY are discussed above and are fully incorporated here. Although BEREZHNOY renders a method for reducing or preventing progression of a non-small cell lung cancer (NSCLC) of claim 141 (from which claim 142 depends) obvious as discussed above, BEREZHNOY does not expressly state that the non-small cell lung cancer (NSCLC) is squamous or non- squamous NSCLC.
CAMPBELL is directed to combination product comprising: a multispecific antibody that binds ICOS and PD-L1, and an anti-CTLA-4 antibody or an anti-PD-1 antibody. See claim 21. CAMPBELL also teaches a bispecific antibody specifically binds to hPD-L1 and another target antigen selected from immune checkpoint inhibitors (such as CD137). See paragraph 0472. Thus, CAMPBELL renders a combination treatment of a bispecific antibody binding CD137 and PD-L1 and a PD-1 inhibitor obvious.
Regarding claim 142, CAMPBELL teaches the treatment of non-small cell lung cancer (squamous and non-squamous. See paragraph 0518.
Thus, BEREZHNOY’s and CAMPBELL’s teachings of combination treatments that include a PD-1 inhibitor and a multispecific antibody targeting CD137 and PD-L1, which CAMPBELL teaches can treat squamous or non- squamous NSCLC render claim 142 obvious.
Regarding claim 146, CAMPBELL teaches a method of treating a cancer in a patient, wherein the cancer is or has been characterised as being refractory to treatment. See Sentence 68, paragraph 0821.
Regarding claim 147, CAMPBELL teaches that administration can be systemic or local. See paragraph 1118.
At the effective filing date of the present claims, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of BEREZHNOY, HASHIMOTO, and CAMPBELL. The artisan would have been motivated to use the methods of the present claims because BEREZHNOY teaches the claimed combination therapy and provides “improved compositions capable of more vigorously stimulating and directing the body's immune system to attack cancer cells while avoiding toxicities associated with antibodies that exhibit high activity in the absence of cross-linking” (see BEREZHNOY at SUMMARY, paragraph 0005, p. 2), and CAMPBELL teaches “antibodies for use in stimulating a patient's immune system, especially the effector T cell response, and has applications in the field of immuno-oncology, especially treatment of tumours” (see CAMPBELL at paragraph 0001). The artisan would have a reasonable expectation of success with the treatment of cancer with the claimed methods from the teachings of BEREZHNOY and CAMPBELL.
Claims 24, 26, 33 – 34, 36 – 37 and 123 are rejected under 35 U.S.C. 103 as being unpatentable over BEREZHNOY as applied to claims 1, 6, 13, 22, 25, 54 – 55, 119, 121, 133, 140 – 141, and 143 – 145 above, and further in view of ALTINTAS (WO 2019/025545 A1, published 02/07/2019, an IDS reference submitted 12/17/2024).
The teachings of BEREZHNOY are discussed above and fully incorporated here. Although BEREZHNOY teaches the method of present claim 1, from with claims 24, 26, 33 – 34, 36 – 37 and 123, depend from, either directly or indirectly, BEREZHNOY does not expressly teach the limitation of present claims 24, 26, 33 – 34, 36 – 37 and 123.
ALTINTAS is directed to binding agents such as bispecific antibodies binding to human PD-L1 and human CD137 in the treatment of cancer (pages 4, line 34 – page 5, line 4).
Regarding claim 24, ALTINTAS discloses that the bispecific antibody comprises a first and second heavy chain constant region (CH) comprising a CH3 region and wherein the two CH3 regions comprise asymmetrical mutations. See page 51, lines 3 – 6.
Regarding claim 26, ALTINTAS discloses that the binding agent according to claim 54 includes the amino acid in the position corresponding to F405 in a human IgGl heavy chain according to EU numbering is L in said first heavy chain constant region (CH), and the amino acid in the position corresponding to K409 in a human IgGl heavy chain according to EU numbering is R in said second heavy chain constant region (CH), or (ii) the amino acid in the position corresponding to K409 in a human IgGl heavy chain according to EU numbering is R in said first heavy chain, and the amino acid in the position corresponding to F405 in a human IgGl heavy chain according to EU numbering is L in said second heavy chain.
Regarding claim 33, ALTINTAS discloses that the binding agent has at least one of said first and second heavy chain constant region (CH) one or more amino acids in the positions corresponding to positions L234, L235, D265, N297, and P331 in a human IgGl heavy chain according to EU numbering, are not L, L, D, N, and P, respectively. See claim 61.
Regarding claim 34, ALTINTAS discloses that the binding agent has positions corresponding to positions L234 and L235 in a human IgG1 heavy chain according to EU numbering are F and E, respectively, in said first and second heavy chains. See claim 62.
Regarding claims 36 and 37, ALTINTAS discloses that the binding agent has positions corresponding to positions L234, L235, and D265 in a human IgGl heavy chain according to EU numbering of both the first and second heavy chain constant regions are F, E, and A, respectively, and wherein (i) the position corresponding to F405 in a human IgGl heavy chain according to EU numbering of the first heavy chain constant regio is L, and the position corresponding to K409 in a human IgGl heavy chain according to EU numbering of the second heavy chain constant region is R, or (ii) the position corresponding to K409 in a human IgGl heavy chain according to EU numbering of the first heavy chain is R, and the position corresponding to F405 in a human IgGl heavy chain according to EU numbering of the second heavy chain is L. See claim 64.
Regarding claim 123, ALTINTAS discloses therapeutically effective amount of a compound of the present invention is about 0.001-10 mg/kg, such as about 0.001-5 mg/kg, for example about 0.001-2 mg/kg, such as about 0.001-1 mg/kg, for instance about 0.001, about 0.01, about 0.1, about 1 or about 10 mg/kg. Another exemplary, non-limiting range for a therapeutically effective amount of a binding agent (e.g. a bispecific antibody) of the present invention is about 0.1-100 mg/kg, such as about 0.1-50 mg/kg, for example about 0.1-20 mg/kg, such as about 0.1-10 mg/kg, for instance about 0.5, about such as 0.3, about 1, about 3, about 5, or about 8 mg/kg. See page 81, line 28 – page 82, line 2. Considering that an average human is approximately 62 kg, a dosage of 100 mg falls within the ranges disclosed by ALTINTAS.
At the effective filing date of the present claims, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of BEREZHNOY and ALTINTAS. The artisan would have been motivated to use the method of claim 1 because BEREZHNOY teaches the claimed combination therapy and provides “improved compositions capable of more vigorously stimulating and directing the body's immune system to attack cancer cells while avoiding toxicities associated with antibodies that exhibit high activity in the absence of cross-linking (see BEREZHNOY at SUMMARY, paragraph 0005, p. 2 and ALTINTAS teaches multispecific antibodies that can bind both PD-L1 and CD137 resulting in conditional activation of (cytotoxic) T cells with an improved toxicology profile compared to current treatment options in the field (see ALTINTAS at p. 2, lines 28 – 30 and p. 3, lines 8 – 10). The artisan would have a reasonable expectation of success with the treatment of cancer with the claimed methods from the teachings of BEREZHNOY and ALTINTAS.
Response to Arguments
On page 9 – 10 of the reply of 03/06/2026, Applicant argues that BEREZHNOY does not teach a combination therapy consisting of ( a multispecific binding agent and (ii) a PD-1 antibody, arguing that “[c]ontrary to the Office's assertion, Berezhnoy does not teach or suggest synergy between CD137 agonism and PD-1 blockade. This conclusion is based on a misreading of Berezhnoy, which never discloses administering a PD-1 inhibitor together with a CD137xPD-L1 bispecific in the absence of a second tumor-targeting CD3-redirecting agent. Berezhnoy instead explains adding a PD-1 inhibitor explicitly depends on the presence of a TAxCD3 bispecific, which induces PD-1 up-regulation” and quotes paragraph 00446, stating that “[t]his passage confirms that a PD-1 inhibitor is not taught as an independent agent for the CD137xPD-L1 bispecific. It is disclosed as an agent when PD-1 up-regulation occurs because of the combination of CD137 x TA and TAXCD3” (fourth paragraph under the heading “35 U.S.C. §103”).
Applicant’s arguments have been fully considered but not found persuasive because BEREZHNOY at paragraph 0048 teaches that “[w]here such combinations are employed, it is specifically contemplated that, one or more of the molecules may be administered to a subject ‘concurrently’ (e.g., a CD137 x TA Binding Molecule may be administered at the same time as a TA x CD3 Binding Molecule and/or a PD-1/PD-L1 Checkpoint Inhibitor is administered) and/or that one or more of the molecules may be administered ‘sequentially’ (e.g., a CD137 x TA Binding Molecule is administered and, at a later time, a TA x CD3 Binding Molecule and/or a PD-1/PD-L1 Checkpoint Inhibitor is administered, or vice versa).” Thus, BEREZHNOY teaches that the CD137 x TA Binding Molecule may in a combination with a TA x CD3 Binding Molecule or a PD-1/PD-L1 Checkpoint Inhibitor, and thus, the TA x CD3 Binding Molecule is not necessarily required in the combination. In other words, BEREZHNOY expressly teaches the combination therapy consisting of a CD137 x TA Binding Molecule and a PD-1/PD-L1 Checkpoint Inhibitor.
On p. 11, second and third paragraphs, of the reply of 03/06/2026, Applicant argues that “[t]he Office's reliance on Hashimoto is also misplaced. Although Hashimoto discusses
combinations of monospecific CD137 agonists with PD-1 inhibitors, it does not teach or suggest combining a PD-L1 xCD137 bispecific with a PD-1 inhibitor. Hashimoto's checkpoint-inhibitor discussion concerns monospecific anti-CD137 antibodies, not PD-L1xCD137 bispecifics, and nowhere does it teach or suggest the claimed two-agent regimen. Similarly, Garralda has not been shown to teach or suggest the claimed two-agent combination therapy.”
Applicant’s argument is not persuasive because BEREZHNOY teaches the two-agent combination as discussed above.
On p. 11, under the heading “Campbell” – p. 12, first paragraph, Applicant argues that “Applicant relies on their discussion above as to Berezhnoy in view of Hashimoto and Garralda. Campbell does not overcome the cited documents' deficiencies. Campbell does not teach the claimed multispecific binding agent (CD137xPD-L1) and (ii) a PD-1 antibody. Campbell is directed to an ICOSxPD-L1 bispecific, not the presently claimed multispecific binding agent together with a PD-1 antibody, and nothing in Campbell teaches or suggests such a structure or combination. Campbell's formats and biology relate to ICOS agonism paired with PD-L1 blockade-not PD-1-and its optional references to other checkpoint inhibitors merely identify background therapeutic agents, not substitutions or structural modifications to its bispecific design. The Office's reliance on Campbell appears to rest on the fact that Campbell includes PD-L1 as one arm, but nothing in Campbell teaches one skilled in the art to select it to arrive at the claimed combination. Thus, Campbell cannot cure the absence of any teaching or motivation in the cited art to arrive at the claimed multispecific binding agent plus PD-1 antibody.”
Applicant’s argument is not persuasive because BEREZHNOY teaches the claimed combination therapy as discussed above, and CAMPBELL teaches the limitations of present claims 142, 146 and 147. Nonetheless, CAMPBELL is directed to combination product comprising: a multispecific antibody that binds ICOS and PD-L1, and an anti-CTLA-4 antibody or an anti-PD-1 antibody. See CAMPBELL at claim 21. CAMPBELL teaches a bispecific antibody specifically binds to hPD-L1 and another target antigen selected from immune checkpoint inhibitors (such as CD137). See CAMPBELL at paragraph 0472. Thus, CAMPBELL renders a combination treatment of a bispecific antibody binding CD137 and PD-L1 and a PD-1 inhibitor obvious as discussed above.
On p. 12, second paragraph under the heading “Altintas” of the reply, “Applicant relies on their discussion above as to deficiencies in Berezhnoy when considered in view of Hashimoto and Garralda. Altintas does not overcome those deficiencies. As the Office itself acknowledges, Altintas does not disclose the addition of a PD-1 inhibitor and as noted above nothing in Berzhnoy teaches one to pick and choose a PD-1 inhibitor from unrelated alternatives disclosed.”
Applicant’s argument is not persuasive because BEREZHNOY and ALTINTAS each teaches the claimed combination therapy as discussed above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 119, 121, 123, 133, and 140 – 147 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 12 of U.S. Patent No. 10,968,280 in view of BEREZHNOY, CAMPBELL and ALTINTAS.
Patented claim 1 recites a multispecific antibody comprising a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1, wherein the second antigen-binding region inhibits the binding of human PD-L1 to human PD-L1, wherein (i) the first antigen-binding region comprises a first heavy chain variable region (VH) and a first light chain variable region (VL), wherein the first VH comprises the amino acid sequence as set forth in SEQ ID NO: 15, . . . and (ii) the second antigen-binding region comprises a second heavy chain variable region (VH) and a second light chain variable region (VL), wherein the second VH comprises the amino acid sequence as set forth in SEQ ID NO: 17, . . .
Patented claim 2 recites that the multispecific antibody of claim 1, wherein (i) the first VL comprises the amino acid sequence as set forth in SEQ ID NO: 16; and (ii) the second VL comprises the amino acid sequence as set forth in SEQ ID NO: 21.
Patented SEQ ID NO: 15 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; patented SEQ ID NO: 16 discloses the anti-CD137 CDRs of present 6, 8, and the sequence GAS; patented SEQ ID NO: 17 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 12 – 14; and patented SEQ ID NO: 21 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 16, 18, and the sequence DDN of the present claims. See Appendix of record.
The main difference between the present claims and the patented claims is that the present claims recite a method for reducing or preventing progression of a tumor or treating cancer by administering a combination therapy consisting of the multispecific binding agent and a PD-1 inhibitor. However, BEREZHNOY discloses this difference. The teachings of BEREZHNOY, CAMPBELL, and ALTINTAS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above and of record.
Because the patented claims recite a multispecific antibody comprising a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1 and BEREZHNOY teaches a combination treatment that includes the multispecific antibody and a PD-1 inhibitor in a method of treating cancer, it would have been obvious to one having ordinary skill in the art to use the patented multispecific antibody in the method of the present claims.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 119, 121, 123, 133, and 140 – 147 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 19 of U.S. Patent No. 11,459,395 in view of BEREZHNOY, CAMPBELL and ALTINTAS.
Patented claim 1 recites bispecific antibody comprising a single antibody that has two arms comprising different antigen binding regions, wherein the first arm comprises a first antigen-binding region capable of binding to human CD137 and wherein the second arm comprises a second antigen-binding region capable of binding to human PD-L1.
Patented claim 3 recites that 3. The bispecific antibody according to claim 1, wherein said second antigen-binding region capable of binding to human PD-L1 comprises a heavy chain variable region (VH) and a variable region (VL), wherein the VH comprises the amino acid sequence as set forth in SEQ ID NO: 17, and wherein the VL comprises the amino acid sequence as set forth in SEQ ID NO: 21.
Patented SEQ ID NO: 17 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 12 – 14; and patented SEQ ID NO: 21 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 16, 18, and the sequence DDN of the present claims. See Appendix of record.
The main difference between the present claims and the patented claims is that the present claims recite a method for reducing or preventing progression of a tumor or treating cancer by administering a combination therapy consisting of the multispecific binding agent and a PD-1 inhibitor. Also, the anti-CD137 CDRs of the present claim are not disclosed in the patented claims. However, BEREZHNOY discloses these differences. The teachings of BEREZHNOY, CAMPBELL and ALTINTAS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above and of record.
Because the patented claims recite a bispecific antibody comprising a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1 and BEREZHNOY teaches a combination treatment that includes the multispecific antibody and a PD-1 inhibitor in a method of treating cancer, it would have been obvious to one having ordinary skill in the art to use the patented multispecific antibody in the method of the present claims.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 119, 121, 123, 133, and 140 – 147 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 71, 73, 87, 90, 92, 94, 96, 98, 100, 102, 104 – 139 of copending Application No. 17/172,698 in view of BEREZHNOY, CAMPBELL, and ALTINTAS.
Copending claim 94 recites a nucleic acid or a set of nucleic acids encoding a multispecific antibody, wherein the multispecific antibody comprises: (I) a first antigen-binding region capable of binding to human CD137, . . . (II) a second antigen-binding region capable of binding to human PD-L1, . . .
Copending claim 90 recites that the VH of the second antigen-binding region comprises the amino acid sequence set forth in SEQ ID NO:17.
Copending claim 92 recites that the VL of the second antigen-binding region comprises the amino acid sequence set forth in SEQ ID NO:21.
Copending claim 102 recites that the VH of the first antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:15.
Copending claim 104 recites that the first antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:16.
Copending SEQ ID NO: 15 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; copending SEQ ID NO: 16 discloses the anti-CD137 CDRs of present SEQ ID NOs: 6, 8, and the sequence GAS; copending SEQ ID NO: 17 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 12 – 14; and copending SEQ ID NO: 21 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 16, 18, and the sequence DDN of the present claims. See Appendix of record.
The main difference between the present claims and the copending claims is that the present claims recite a method for reducing or preventing progression of a tumor or treating cancer by administering a combination therapy consisting of the multispecific binding agent and a PD-1 inhibitor. However, BEREZHNOY discloses this difference. The teachings of BEREZHNOY, CAMPBELL, and ALTINTAS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above and of record.
Because the copending claims recite a multispecific antibody comprising a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1 and BEREZHNOY teaches a combination treatment that includes the multispecific antibody and a PD-1 inhibitor in a method of treating cancer, it would have been obvious to one having ordinary skill in the art to use the patented multispecific antibody in the method of the present claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 119, 121, 123, 133, and 140 – 147 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 94 - 115 of copending Application No. 17/172,700 in view of BEREZHNOY, CAMPBELL, and ALTINTAS.
Copending claim 94 recites a method of treating cancer in a subject in need thereof, the method comprising administering a multispecific antibody to the subject, wherein the multispecific antibody comprises a first antigen- binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1, . . .
Copending claim 108 recites that the VH of the first antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:15.
Copending claim 109 recites that wherein the VL of the first antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:16.
Copending claim 110 recites that the VH of the second antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:17.
Copending claim 111 recites that the VL of the second antigen binding region comprises the amino acid sequence set forth in SEQ ID NO:21.
Copending SEQ ID NO: 15 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; copending SEQ ID NO: 16 discloses the anti-CD137 CDRs of present SEQ ID NOs: 6, 8, and the sequence GAS; copending SEQ ID NO: 17 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 12 – 14; and copending SEQ ID NO: 21 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 16, 18, and the sequence DDN of the present claims. See Appendix of record.
The main difference between the present claims and the copending claims is that the present claims recite that the method includes a PD-1 inhibitor with the multispecific antibody in a combination therapy. The present claims also recite various mutations (i.e. claim 38) to the antibody. However, BEREZHNOY and ALTINTAS disclose these differences. The teachings of BEREZHNOY, CAMPBELL, and ALTINTAS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above and of record.
Because the copending claims recite a multispecific antibody comprising a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1 and BEREZHNOY and ALTINTAS disclose this multispecific antibody and with a PD-1 inhibitor in a method of treating cancer, it would have been obvious to one having ordinary skill in the art to use the copending method with the PD-1 inhibitor of the present claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 119, 121, 123, 133, and 140 – 147 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6, 7, 9, 12, 16, 22, 42, 48 – 51, and 76 – 95 of copending Application No. 17/289,602 in view of BEREZHNOY, CAMPBELL and ALTINTAS.
Copending claim 1 recites a pharmaceutical formulation comprising: a) a multispecific antibody comprising a first binding arm capable of binding to human CD137 (4-1BB) and a second binding arm capable of binding to human PD-L1 (CD274) . . .
Copending claim 22 recites that the first antigen biding region comprises a first heavy chain variable region (VH) comprising an amino acid sequence at least 85% identical to the sequence set forth in SEQ ID NO: 15; and a first light chain variable region (VL) comprising an amino acid sequence at least 85% identical to the sequence set forth in SEQ ID NO: 16, and- the second antigen-binding region comprises a second VH comprising an amino acid at least 85% identical to the sequence set forth in SEQ ID NO: 17; and a second (VL comprising an amino acid sequence at least 85% identical to the sequence set forth in SEQ ID NO: 21.
Copending SEQ ID NO: 15 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; copending SEQ ID NO: 16 discloses the anti-CD137 CDRs of present SEQ ID NOs: 6, 8, and the sequence GAS; copending SEQ ID NO: 17 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 12 – 14; and copending SEQ ID NO: 21 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 16, 18, and the sequence DDN of the present claims. See Appendix of record.
The main difference between the present claims and the copending claims is that the present claims recite a method for reducing or preventing progression of a tumor or treating cancer by administering a combination therapy consisting of the multispecific binding agent and a PD-1 inhibitor. However, BEREZHNOY discloses these differences. The teachings of BEREZHNOY, HASHIMOTO, CAMPBELL, and ALTINTAS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above and of record.
Because the copending claims recite a multispecific antibody comprising a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1 and BEREZHNOY teaches a combination treatment that includes the multispecific antibody and a PD-1 inhibitor in a method of treating cancer, it would have been obvious to one having ordinary skill in the art to use the patented multispecific antibody in the method of the present claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 119, 121, 123, 133, and 140 – 147 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 4, 13 – 18, 28 – 34, 43 – 48, 53 – 55, 57, 58, 63, 64, 66, and 71 of copending Application No. 17/759,906 in view of BEREZHNOY, CAMPBELL and ALTINTAS.
Copending claim 1 recites a method for treating a subject comprising administering to the subject: a. a peptide or protein comprising an epitope for inducing an immune response against an antigen in the subject or a polynucleotide encoding the peptide or protein; and b. a binding agent comprising a first antigen-binding region binding to PD-L1 and a second antigen-binding region binding to CD137, or a polynucleotide encoding the binding agent.
Copending claim 18 recites that said first antigen-binding region binding to PD-L 1 comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the sequence as set forth in SEQ ID NO: 10 and the VL comprises the sequence as set forth in SEQ ID NO: 14.
Copending claim 30 recites that said second antigen-binding region binding to CD137 comprises a heavy chain variable region (VH), wherein the VH comprises the sequence as set forth in SEQ ID NO: 1 or 8.
Copending claim 32 recites that said second antigen-binding region binding to CD 137 comprises a light chain variable region (VL), wherein the VL comprises the sequence as set forth in SEQ ID NO: 5 or 9.
Copending SEQ ID NO: 1 or 8 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; copending SEQ ID NO: 5 or 9 discloses the anti-CD137 CDRs of present SEQ ID NOs: 6, 8, and the sequence GAS; copending SEQ ID NO: 10 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 12 – 14; and copending SEQ ID NO: 14 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 16, 18, and the sequence DDN of the present claims. See Appendix of record.
The main difference between the present claims and the copending claims is that the present claims recite a method for reducing or preventing progression of a tumor or treating cancer by administering a combination therapy consisting of the multispecific binding agent and a PD-1 inhibitor. The present claims also recite various mutations (i.e. claim 38) to the antibody. However, BEREZHNOY and ALTINTAS disclose these differences. The teachings BEREZHNOY, HASHIMOTO, CAMPBELL, and ALTINTAS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above and of record.
Because the copending claims recite a binding agent comprising a first antigen-binding region binding to PD-L1 and a second antigen-binding region binding to CD137 and BEREZHNOY and ALTINTAS disclose this binding agent and with a PD-1 inhibitor in a method of treating cancer, it would have been obvious to one having ordinary skill in the art to use the binding agent of the copending claims in a method with the PD-1 inhibitor of the present claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 119, 121, 123, 133, and 140 – 147 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 9, 11, 18, 22, 30, 33, 53, 56, 62, 66, 71, 97, 99 – 103, and 110 of copending Application No. 17/795,318 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claim 1 recites a method for reducing or preventing progression of a tumor or treating cancer in a human subject, comprising administering to said human subject, in at least one treatment cycle, a binding agent in a suitable amount, comprising a first binding region binding to human CD137, such as human CD137 having the sequence set forth in SEQ ID NO: 24, and a second binding region binding to human PD-L1, such as human PD-L1 having the sequence set forth in SEQ ID NO: 26.
Copending claim 9 recites that the first binding region comprises a heavy chain variable region (VH) comprising an amino acid sequence having at least 90
Copending SEQ ID NO: 1 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; copending SEQ ID NO: 5 discloses the anti-CD137 CDRs of present 6, 8, and the sequence GAS; copending SEQ ID NO: 8 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 12 – 14; and copending SEQ ID NO: 12 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 16, 18, and the sequence DDN of the present claims. See Appendix of record.
Copending claim 62 recites that the subject has received prior treatment with checkpoint inhibitor(s), such as agent(s) targeting PD-1/PD-L, such as a PD-1/PD-L1 inhibitor.
Thus, the present claims are rendered obvious by the copending claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 119, 121, 123, 133, and 140 – 147 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 89 – 104 of copending Application No. 17/821,837 in view of BEREZHNOY, CAMPBELL and ALTINTAS.
Copending claim 1 recites a multispecific antibody comprising a first antigen-binding region binding to human CD137 and a second antigen-binding region binding to human PD-L1, wherein the second antigen-binding region inhibits the binding of human PD-L1 to human PD-1.
Copending claim 102 recites that the first antigen-binding region binding to human CD137 compries a VH sequence as set forth in SEQ ID NO: 15 and a VL sequence as set forth in SEQ ID NO: 16.
Copending claim 104 recites that the second antigen-binding region comprises a heavy chain variable region (VH) comprising the sequence as set forth in: SEQ ID NO:17 and a light chain variable region (VL) comprising the sequence as set forth in: SEQ ID NO:21.
Copending SEQ ID NO: 15 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; copending SEQ ID NO: 16 discloses the anti-CD137 CDRs of present SEQ ID NOs: 6, 8, and the sequence GAS; copending SEQ ID NO: 17 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 12 – 14; and copending SEQ ID NO: 21 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 16, 18, and the sequence DDN of the present claims. See Appendix of record.
The main difference between the present claims and the copending claims is that the present claims recite a method for reducing or preventing progression of a tumor or treating cancer by administering a combination therapy consisting of the multispecific binding agent and a PD-1 inhibitor. However, BEREZHNOY discloses this difference. The teachings BEREZHNOY, CAMPBELL and ALTINTAS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above and of record.
Because the copending claims recite a multispecific antibody comprising a first antigen-binding region capable of binding to human CD137 and a second antigen-binding region capable of binding to human PD-L1 and BEREZHNOY teaches a combination treatment that includes the multispecific antibody and a PD-1 inhibitor in a method of treating cancer, it would have been obvious to one having ordinary skill in the art to use the patented multispecific antibody in the method of the present claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 119, 121, 123, 133, and 140 – 147 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, 13, 20, 28, 32, 50, 51, 53, 57, 60, 62 – 64, 98, 70, 85, 99, and 116 of copending Application No. 18/038,818 in view of BEREZHNOY, CAMPBELL and ALTINTAS.
Copending claim 1 recites a method for reducing or preventing progression of a tumor or treating cancer in a subject, comprising administering to the subject combined treatment with i} a binding agent comprising a first binding region binding to human CD137, and a second binding region binding to human PD-Li; and ii) a taxane chemotherapeutic agent.
Copending claim 6 recites that a) the first binding region comprises a heavy chain variable region (VH) comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 2, 3, and 4, respectively, and a light chain variable region (VL) comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 6, GAS, 7, respectively; and b) the second antigen-binding region comprises a heavy chain variable region (VH) comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 9, 10, 11 respectively, and a light chain variable region (VL) comprising the CDR1, CDR2, and CDR3 sequences set forth in SEQ ID NO: 13, DDN, 14, respectively.
The CDRs of copending claim 6 are identical to the CDRs of claims 1, 8, and 133.
The main difference between the present claims and the copending claims is that the present claims recite a combination therapy with PD-1 inhibitor. However, BEREZHNOY discloses this difference. The teachings BEREZHNOY, CAMPBELL, and ALTINTAS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above and of record.
Because the copending claims recite a method for reducing or preventing progression of a tumor or treating cancer in a subject, comprising administering to the subject combined treatment with i} a binding agent comprising a first binding region binding to human CD137, and a second binding region binding to human PD-L1 and BEREZHNOY disclose this binding agent and with a PD-1 inhibitor in a method of treating cancer, it would have been obvious to one having ordinary skill in the art to use the binding agent of the copending claims with the PD-1 inhibitor in the method of the present claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 119, 121, 123, 133, and 140 – 147 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over 1, 3, 5, 6, 9, 10, 12, 13, 15, 18, 22, 25, 36, 44, 48, 66, 68, 69, 71, 76, 80, 86, 89 of copending Application No. 18/570,257 in view of BEREZHNOY, CAMPBELL, and ALTINTAS.
Copending claim 1 recites method for preventing progression of a tumor or treating cancer in a subject, comprising administering to said subject a binding agent comprising a first antigen-binding region binding to human CD137 and a second antigen-binding region binding to human PD-L1 . . .
Copending claim 25 recites that the first antigen-binding region comprises a heavy chain variable region (VH) comprising an amino acid sequence at least 90% identical to SEQ ID NO: 1 and a light chain variable region (VL) region comprising an amino acid sequence at least 90%; identical to SEQ ID NO: 5; and b) the second antigen-binding region comprises a heavy chain variable region (VH) comprising an amino acid sequence at least 90% identical to SEQ ID NO: 8 and a light chain variable region (VL) region comprising an amino acid sequence at least 90%; identical to SEQ ID NO: 12.
Copending SEQ ID NO: 1 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; copending SEQ ID NO: 5 discloses the anti-CD137 CDRs of present SEQ ID NOs: 6, 8, and the sequence GAS; copending SEQ ID NO: 8 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 12 – 14; and copending SEQ ID NO: 12 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 16, 18, and the sequence DDN of the present claims. See Appendix of record.
The main difference between the present claims and the copending claims is that the present claims recite the binding agent in a combination therapy with a PD-1 inhibitor. However, BEREZHNOY discloses this difference. The teachings BEREZHNOY, CAMPBELL and ALTINTAS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above and of record.
Because the copending claims recite a method for preventing progression of a tumor or treating cancer in a subject, comprising administering to said subject a binding agent comprising a first antigen-binding region binding to human CD137 and a second antigen-binding region binding to human PD-L1 and BEREZHNOY disclose this binding agent and with a PD-1 inhibitor in a method of treating cancer, it would have been obvious to one having ordinary skill in the art to use the binding agent of the copending claims with the PD-1 inhibitor in the method of the present claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 119, 121, 123, 133, and 140 – 147 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 98 of copending Application No. 18/698,354 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claim 1 recites a method for reducing or preventing progression of a tumor or treating cancer in a subject, comprising administering to said subject a binding agent prior to, simultaneously with, or after administration of an antibody binding to Programmed Death-1 (PD-1), or an antigen-binding fragment thereof, wherein the binding agent comprises a first binding region binding to CD137 and a second binding region binding to PD-L1 . . .
Copending claim 11 recites that the first binding region of the binding agent comprises a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 1 and a light chain variable region (VL) region comprising the amino acid sequence set forth in SEQ ID NO: 5; and b) the second binding region of the binding agent comprises a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 11 and a light chain variable region (VL) region comprising the amino acid sequence set forth in SEQ ID NO:15.
Copending SEQ ID NO: 1 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; copending SEQ ID NO: 5 discloses the anti-CD137 CDRs of present SEQ ID NOs: 6, 8, and the sequence GAS; copending SEQ ID NO: 11 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 12 – 14; and copending SEQ ID NO: 15 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 16, 18, and the sequence DDN of the present claims. See Appendix of record.
Thus, the present claims are rendered obvious by the copending claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54, 55, 60, 119, 121, 123, 133, and 140 – 147 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 153 of copending Application No. 18/861,665 in view of BEREZHNOY, CAMPBELL, and ALTINTAS.
Copending claim 1 recites a method for reducing progression or preventing progression of a tumor or treating cancer in a subject, said method comprising administering to said subject i) a binding agent comprising at least one binding region binding to CD27; and ii) a PD1/PD-L1 inhibitor.
Copending claim 73 recites that the antibody binding to PD1 comprises a heavy chain having the sequence as set forth in SEQ ID NO: 139, and a light chain having the sequence as set forth in SEQ ID NO: 140.
Copending claim 90 recites that the PD1/PD-L1 inhibitor is a PD-L1 inhibitor comprising a first binding region binding to CD137 and a second binding region binding to PD- L1.
Copending claim 92 recites that the first binding region of the PD-L1 inhibitor comprises a heavy chain variable region (VH) comprising the CDR1, CDR2, and CDR3 sequences of SEQ ID NO: 79, and a light chain variable region (VL) comprising the CDR1, CDR2, and CDR3 sequences of SEQ ID NO: 83; and b) the second binding region of the PD-L1 inhibitor comprises a heavy chain variable region (VH) comprising the CDR1, CDR2, and CDR3 sequences of SEQ ID NO: 86, and a light chain variable region (VL) comprising the CDR1, CDR2, and CDR3 sequences of SEQ ID NO: 90.
Copending SEQ ID NO: 79 discloses the anti-CD137 CDRs of present SEQ ID NOs: 2 – 4; copending SEQ ID NO: 83 discloses the anti-CD137 CDRs of present SEQ ID NOs: 6, 8, and the sequence GAS; copending SEQ ID NO: 86 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 12 – 14; and copending SEQ ID NO: 90 discloses the anti-PD-L1 CDRs of present SEQ ID NOs: 16, 18, and the sequence DDN of the present claims. See Appendix of record.
Copending SEQ ID NO: 139 discloses SEQ ID NOs: 104, 101, and 100; and copending SEQ ID NO: 140 discloses SEQ ID NO: 107, QAS, and SEQ ID NO: 105. See Appendix of record.
The main difference between the present claims and the copending claims is that the present claims recite the binding agent in a combination therapy with a PD-1 inhibitor. However, BEREZHNOY discloses this difference. The teachings BEREZHNOY, CAMPBELL and ALTINTAS and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above and of record.
Because the copending claims recite a method for reducing progression or preventing progression of a tumor or treating cancer in a subject, said method comprising administering to said subject i) a binding agent comprising at least one binding region binding to CD27; and ii) a PD1/PD-L1 inhibitor, wherein the PD1/PD-L1 inhibitor is a PD-L1 inhibitor comprising a first binding region binding to CD137 and a second binding region binding to PD- L1 and BEREZHNOY discloses this binding agent with a PD-1 inhibitor in a method of treating cancer, it would have been obvious to one having ordinary skill in the art to use the binding agent of the copending claims with the PD-1 inhibitor in the method of the present claims.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
On page 13 – 14 of the reply of 03/06/2026, Applicant argues that “[t]he obviousness-type double patenting rejections all rely on the same underlying combination of claims to a PD-L1 xCD137 bispecific in view of Berezhnoy, Hashimoto, Campbell, and Altintas that form the basis of the § 103 rejections. As explained above, none of these documents-individually or in combination-teach or suggest the claimed two-agent combination therapy consisting of (i) a multispecific binding agent and (ii) a PD-1 antibody. For the same reasons that the § 103 rejections fail, the OTDP rejections likewise all fail. As further detailed in Applicants' § 103 traversal, Berezhnoy does not teach a skilled artisan to exclude the TAxCD3 bispecific and instead add a PD-1 inhibitor to arrive at the claimed combination therapy, and none of the other cited documents remedy this deficiency. Because all the double-patenting rejections depend on the same combined teachings of the PD-L1 xCD137 bispecific antibody in view of Berezhnoy, Hashimoto, Campbell, and Altintas, they all fail for the same reasons” (last paragraph of p. 13 – second paragraph of p. 14).
The claimed method, including the combination therapy, is obvious in view of the cited references as discussed above and thus, the double patenting rejections are maintained.
Conclusion
Claims 1, 6, 13, 22, 24 – 26, 33 – 34, 36 – 37, 54 – 55, 60, 119, 121, 123, 133 and 140 – 147 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Estella Gustilo whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:30 AM - 5:30 PM.
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, Gregory Emch can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
Prosecution Insights