Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restriction
The response filed on 3/9/26 to the restriction requirement of 1/7/26 has been received. Without traverse, Applicant has elected the following species: anti-CD47 antibody with no Fc mutations and comprising SEQ ID NOs: 5-10, 12, 14, 65, and 66.
Claims 20-42 are pending and are currently under consideration.
Claim Rejections - 35 USC § 103
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.
Claims 20-24 and 39-42 are rejected under 35 U.S.C. 103(a) as being unpatentable over Zhang et al (US 2022/0324971 A1; 10/13/22; 3/6/26 IDS) in view of Tao et al (Oncology Research, 2017, 25: 1579-1587; 9/29/23 IDS) and Mimura et al (Fukushima J Med Sci, 2018, 64(2): 46-53).
Zhang et al teaches an anti-CD47 monoclonal antibody (6F7H1L1(hG4)) and antigen-binding fragment thereof with a heavy chain comprising SEQ ID NO:65 and a light chain comprising SEQ ID NO:66 ([0065], in particular). SEQ ID NO:65 is identical to instant SEQ ID NO:65 and comprises CDRs and VH of instant SEQ ID NOs: 5-7 and 12. SEQ ID NO:66 is identical to instant SEQ ID NO:66 and comprises CDRs and VL of instant SEQ ID NOs: 8-10 and 14. Zhang et al further teaches said antigen-binding fragment as a single-chain antibody ([0128], in particular). Zhang et al further teaches said antibody as humanized, chimeric, or multispecific ([0091], in particular). Zhang et al further teaches said antibody and antigen-binding fragments thereof are to be used to treat a hematological malignancy or a solid tumor, such as lymphoma, colon cancer, breast cancer, Hodgkin lymphoma, and B cell lymphoma ([0123], in particular). Zhang et al further demonstrates administration of said antibody to subjects with breast cancer therapeutically reduces tumor volume (Fig. 18 and Example 10, in particular). Zhang et al further teaches said antibodies provide therapeutic benefit by (1) binding to CD47 and blocking CD47 binding to its ligand SIRPa, which blocks CD47-SIRPa pathway to allow macrophages to perform phagocytosis and (2) exert tumor killing through DC cells and CD8+ T cells ([0004] and [0239], in particular).
Zhang et al does not specifically teach administering anti-CD47 antibody or binding fragment thereof of Zhang et al to subjects with esophageal squamous cell carcinoma in combination with anti-PD-1 or anti-CTLA-4 antibodies. However, these deficiencies are made up in the teachings of Tao et al and Mimura et al.
Tao et al teaches a method of treating subjects with esophageal squamous cell carcinoma comprising administering an anti-CD47 monoclonal antibody that blocks CD47 interaction with its ligand in combination with anti-PD-1 and anti-CTLA-4 checkpoint inhibitory antibodies synergistically inhibits tumor volume and synergistically increases patient survival, as compared to anti-CD47 alone or a combination of anti-PD-1 and anti-CTLA-4 (Figure 4, in particular). Tao et al further teaches that in addition to increasing proinflammatory response and increased CD8+ T-cell infiltration of tumor tissue, treatment of CD8+ T cells with the anti-CD47 antibody results in an increase in PD-1 and CTLA-4 expression of the cells (page 1581 and Figure 3, in particular) - which are therapeutically targeted by anti-PD-1 and anti-CTLA-4.
Mimura et al teaches the anti-human CTLA-4 monoclonal antibody ipilimumab and the anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab have demonstrated tumor shrinkage and improved overall survival in patient with multiple cancer types (left column on page 46, in particular). Mimura et al further teaches studies administering the anti-PD-1 monoclonal antibody nivolumab to human esophageal squamous cell carcinoma patents that are refractory or intolerant to standard chemotherapy exhibited complete response or partial response to nivolumab (right column on page 49, in particular). Mimura et al further describes combination of anti-PD-1/anti-PD-L1 mAb with treatment such as anti-CTLA-4 mAb may be an “ideal and reasonable strategy” for esophageal squamous cell carcinoma therapy (left column on page 52, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to treat human subjects with esophageal squamous cell carcinoma comprising administering the anti-CD47 antibody of Zhang et al in combination with anti-CTLA-4 monoclonal antibody ipilimumab and the anti-PD-1 monoclonal antibody nivolumab or pembrolizumab of Mimura et al because: Zhang et al teaches said anti-CD47 antibody functions by blocking interaction with CD47 to its ligand ([0004] and [0239], in particular) and is to treat solid tumors ([0123], in particular); Tao et al teaches a method of treating subjects with the solid tumor esophageal squamous cell carcinoma comprising administering an anti-CD47 monoclonal antibody that blocks CD47 interaction with its ligand in combination with anti-PD-1 and anti-CTLA-4 checkpoint inhibitory antibodies synergistically inhibits tumor volume and synergistically increases patient survival (Figure 4, in particular); Tao et al teaches that in addition to increasing proinflammatory response and increased CD8+ T-cell infiltration of tumor tissue, treatment of CD8+ T cells with the anti-CD47 antibody results in an increase in PD-1 and CTLA-4 expression of the cells (page 1581 and Figure 3, in particular) - which are therapeutically targeted by anti-PD-1 and anti-CTLA-4; Mimura et al teaches the anti-human CTLA-4 monoclonal antibody ipilimumab and the anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab have demonstrated tumor shrinkage and improved overall survival in patient with multiple cancer types (left column on page 46, in particular); Mimura et al teaches studies administering the anti-PD-1 monoclonal antibody nivolumab to human esophageal squamous cell carcinoma patents that are refractory or intolerant to standard chemotherapy exhibited complete response or partial response to nivolumab (right column on page 49, in particular); and Mimura et al describes combination of anti-PD-1/anti-PD-L1 mAb with treatment such as anti-CTLA-4 mAb may be an “ideal and reasonable strategy” for esophageal squamous cell carcinoma therapy (left column on page 52, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 20-27, 31-34, 36, 37, and 39-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (US 2022/0324971 A1; 10/13/22; 3/6/26 IDS) in view of Tao et al (Oncology Research, 2017, 25: 1579-1587; 9/29/23 IDS) and Mimura et al (Fukushima J Med Sci, 2018, 64(2): 46-53) as applied to claims 20-24 and 39-42 above, and further in view of Li et al (US 2019/0185569 A1; 6/20/19; 3/6/26 IDS).
Teachings of Zhang et al, Tao et al, and Mimura et al are discussed above.
Teachings of Zhang et al, Tao et al, and Mimura et al do not teach administering the anti-CTLA-4 X anti-PD-1 bispecific antibodies. However, these deficiencies are made up in the teachings of Li et al.
Li et al teaches anti-CTLA-4 X anti-PD-1 bispecific antibodies comprising a VH immunoglobulin domain comprising SEQ ID NO:16 or 20 (SEQ ID NO:16 is the same as instant SEQ ID NOs: 87; SEQ ID NO:20 is the same as instant SEQ ID NOs: 121 and 129), a VL immunoglobulin domain comprising SEQ ID NO: 22 (same as instant SEQ ID NOs: 122 and 130) targeting PD-1, and a VH scFv domain comprising SEQ ID NO: 2, 6, or 10 (same as instant SEQ ID NOs: 95, 135, and 133), and a VL scFv domain comprising SEQ ID NO:4, 8, or 12 (same as instant SEQ ID NO: 96, 136, and 134) targeting CTLA-4 ([0044]-[0047], in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the anti-CTLA-4 and anti-PD-1 antibodies are administered as anti-CTLA-4 X anti-PD-1 bispecific antibodies because it is conventional and routine to administer two therapeutic antibodies as a single bispecific reagent.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the anti-CTLA-4 X anti-PD-1 bispecific antibodies of Li et al are substituted in place of the anti-CTLA-4 and anti-PD-1 antibodies of the combined method because the antibodies of the combined method are to treat cancer and Li et al teaches the anti-CTLA-4 X anti-PD-1 bispecific antibodies are to treat cancer. This is an example of s simple substitution of the anti-CTLA-4 X anti-PD-1 bispecific antibodies of Li et al in place of the anti-CTLA-4 and anti-PD-1 antibodies of the combined method with an expectation of success. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 20-29, 31-34, 36, and 38-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (US 2022/0324971 A1; 10/13/22; 3/6/26 IDS) in view of Tao et al (Oncology Research, 2017, 25: 1579-1587; 9/29/23 IDS) and Mimura et al (Fukushima J Med Sci, 2018, 64(2): 46-53) as applied to claims 20-24, 31-34, and 39-42 above, and further in view of Xia et al (US 2022/0275089 A1; 9/1/22; 3/6/26 IDS).
Teachings of Zhang et al, Tao et al, and Mimura et al are discussed above.
Teachings of Zhang et al, Tao et al, and Mimura et al do not teach administering the anti-CTLA-4 X anti-PD-1 bispecific antibodies. However, these deficiencies are made up in the teachings of Xia et al.
Xia et al teaches anti-CTLA-4 X anti-PD-1 bispecific antibodies comprising a VH immunoglobulin domain comprising SEQ ID NO:14 or 18 (same as instant SEQ ID NOs: 87 and 129) or a heavy domain comprising SEQ ID NO:40 (same as instant SEQ ID NOs: 82 and 139) and a VL immunoglobulin domain comprising SEQ ID NO: 16 or 20 (same as instant SEQ ID NOs: 88 and 130) or a light chain comprising SEQ ID NO:24 (same as instant SEQ ID NOs:80 and 84) targeting PD-1, and a VH scFv domain comprising SEQ ID NO: 2, 41, 10, 43, or 6 (same as instant SEQ ID NOs: 95, 135, 133, 137, and 131), and a VL scFv domain comprising SEQ ID NO:4, 42, 12, 44, or 8 (same as instant SEQ ID NO: 96, 136, 134, 138, and 132 ) targeting CTLA-4 ([0056]-[0057] and [0103], in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the anti-CTLA-4 and anti-PD-1 antibodies are administered as anti-CTLA-4 X anti-PD-1 bispecific antibodies because it is conventional and routine to administer two therapeutic antibodies as a single bispecific reagent.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the anti-CTLA-4 X anti-PD-1 bispecific antibodies of Xia et al are substituted in place of the anti-CTLA-4 and anti-PD-1 antibodies of the combined method because the antibodies of the combined method are to treat cancer and Xia et al teaches the anti-CTLA-4 X anti-PD-1 bispecific antibodies are to treat cancer. This is an example of s simple substitution of the anti-CTLA-4 X anti-PD-1 bispecific antibodies of Xia et al in place of the anti-CTLA-4 and anti-PD-1 antibodies of the combined method with an expectation of success. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claims 20-24, 35, 41, and 42 are rejected under 35 U.S.C. 103(a) as being unpatentable over Zhang et al (US 2022/0324971 A1; 10/13/22; 3/6/26 IDS) in view of Feliz-Mosquea et al (Breast Cancer Research and Treatment, 2018, 172: 69-82).
Zhang et al teaches an anti-CD47 monoclonal antibody (6F7H1L1(hG4)) and antigen-binding fragment thereof with a heavy chain comprising SEQ ID NO:65 and a light chain comprising SEQ ID NO:66 ([0065], in particular). SEQ ID NO:65 is identical to instant SEQ ID NO:65 and comprises CDRs and VH of instant SEQ ID NOs: 5-7 and 12. SEQ ID NO:66 is identical to instant SEQ ID NO:66 and comprises CDRs and VL of instant SEQ ID NOs: 8-10 and 14. Zhang et al further teaches said antigen-binding fragment as a single-chain antibody ([0128], in particular). Zhang et al further teaches said antibody as humanized, chimeric, or multispecific ([0091], in particular). Zhang et al further teaches said antibody and antigen-binding fragments thereof are to be used to treat a hematological malignancy or a solid tumor, such as lymphoma, colon cancer, breast cancer, Hodgkin lymphoma, and B cell lymphoma ([0123], in particular). Zhang et al further demonstrates administration of said antibody to subjects with breast cancer therapeutically reduces tumor volume (Fig. 18 and Example 10, in particular). Zhang et al further teaches said antibodies provide therapeutic benefit by (1) binding to CD47 and blocking CD47 binding to its ligand SIRPa, which blocks CD47-SIRPa pathway to allow macrophages to perform phagocytosis and (2) exert tumor killing through DC cells and CD8+ T cells ([0004] and [0239], in particular).
Zhang et al does not specifically teach administering a combination of anti-CD47 antibody or binding fragment thereof and anthracyclines. However, these deficiencies are made up in the teachings of Feliz-Mosquea et al.
Feliz-Mosquea et al teaches therapeutically inhibiting breast cancer growth while preventing cardiac toxicity by administering a combination of anthracyclines and CD47 inhibition therapy to subjects with breast cancer (Abstract and Fig. 2, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to therapeutically treat a patient with breast cancer comprising performing the method of Feliz-Mosquea et al wherein the CD47 inhibition therapy is administering the anti-CD47 antibody of Zhang et al to the breast cancer patient because the method of Feliz-Mosquea et al treats breast cancer comprising inhibiting CD47 and the anti-CD47 antibody is taught by Zhang et al as an inhibitor of CD47 to be used in breast cancer treatment. This is an example of a simple substitution of one known element for another to obtain predictable results. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claims 20-30 are rejected under 35 U.S.C. 103(a) as being unpatentable over Zhang et al (US 2022/0324971 A1; 10/13/22; 3/6/26 IDS) in view of Xiong et al (International Journal of Molecular Sciences, 2018, 19(2900): 1-20).
Zhang et al teaches an anti-CD47 monoclonal antibody (6F7H1L1(hG4)) and antigen-binding fragment thereof with a heavy chain comprising SEQ ID NO:65 and a light chain comprising SEQ ID NO:66 ([0065], in particular). SEQ ID NO:65 is identical to instant SEQ ID NO:65 and comprises CDRs and VH of instant SEQ ID NOs: 5-7 and 12. SEQ ID NO:66 is identical to instant SEQ ID NO:66 and comprises CDRs and VL of instant SEQ ID NOs: 8-10 and 14. Zhang et al further teaches said antigen-binding fragment as a single-chain antibody ([0128], in particular). Zhang et al further teaches said antibody as humanized, chimeric, or multispecific ([0091], in particular). Zhang et al further teaches said antibody and antigen-binding fragments thereof are to be used to treat a hematological malignancy or a solid tumor ([0123], in particular).
Zhang et al does not specifically teach a combination of anti-CD47 antibody or binding fragment thereof and an anti-PD-1/anti-VEGFA bispecific antibody. However, these deficiencies are made up in the teachings of Xiong et al.
Xiong et al teaches a teaches an anti-PD-1/anti-VEGFA bispecific antibody that provides therapeutic benefit to subjects with a solid tumor (Figure 10, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to generate a combination comprising the anti-CD47 antibody of Zhang et al and the anti-PD-1/anti-VEGFA bispecific antibody of Xiong et al to treat solid tumors because both reagents have been shown to treat solid tumors. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
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 20-24 and 39-42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-7, 9, 11, 12, 15, 17, 20, 25, and 31-39 of copending Application No. 17/640005 in view of Tao et al (Oncology Research, 2017, 25: 1579-1587) and Mimura et al (Fukushima J Med Sci, 2018, 64(2): 46-53).
The published copending Application No. 17/640005 is described above as Zhang et al (US 2022/0324971 A1; 10/13/22).
The copending claims and instant claims are drawn to the same anti-CD47 antibodies and methods of administering said antibodies. The copending claims do not specifically recite the antibodies are part of a composition comprising another therapeutic regent or that said composition is administered to a patient. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to treat human subjects with esophageal squamous cell carcinoma comprising administering the anti-CD47 antibody of the copending claims in combination with anti-CTLA-4 monoclonal antibody ipilimumab and the anti-PD-1 monoclonal antibody nivolumab or pembrolizumab of Mimura et al because: the copending antibody functions by blocking interaction with CD47 to its ligand and is to treat solid tumors; Tao et al teaches a method of treating subjects with the solid tumor esophageal squamous cell carcinoma comprising administering an anti-CD47 monoclonal antibody that blocks CD47 interaction with its ligand in combination with anti-PD-1 and anti-CTLA-4 checkpoint inhibitory antibodies synergistically inhibits tumor volume and synergistically increases patient survival (Figure 4, in particular); Tao et al teaches that in addition to increasing proinflammatory response and increased CD8+ T-cell infiltration of tumor tissue, treatment of CD8+ T cells with the anti-CD47 antibody results in an increase in PD-1 and CTLA-4 expression of the cells (page 1581 and Figure 3, in particular) - which are therapeutically targeted by anti-PD-1 and anti-CTLA-4; Mimura et al teaches the anti-human CTLA-4 monoclonal antibody ipilimumab and the anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab have demonstrated tumor shrinkage and improved overall survival in patient with multiple cancer types (left column on page 46, in particular); Mimura et al teaches studies administering the anti-PD-1 monoclonal antibody nivolumab to human esophageal squamous cell carcinoma patents that are refractory or intolerant to standard chemotherapy exhibited complete response or partial response to nivolumab (right column on page 49, in particular); and Mimura et al describes combination of anti-PD-1/anti-PD-L1 mAb with treatment such as anti-CTLA-4 mAb may be an “ideal and reasonable strategy” for esophageal squamous cell carcinoma therapy (left column on page 52, in particular).
This is a provisional nonstatutory double patenting rejection.
Claims 20-27, 31-34, 36, 37, and 39-42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-7, 9, 11, 12, 15, 17, 20, 25, and 31-39 of copending Application No. 17/640005 in view of Tao et al (Oncology Research, 2017, 25: 1579-1587) and Mimura et al (Fukushima J Med Sci, 2018, 64(2): 46-53) as applied to claims 20-24 and 39-42 above, and further in view of Li et al (US 2019/0185569 A1; 6/20/19).
Combination of copending claims, Tao et al, and Mimura et al are discussed above.
Copending claims, Tao et al, and Mimura et al do not teach administering the anti-CTLA-4 X anti-PD-1 bispecific antibodies. However, these deficiencies are made up in the teachings of Li et al.
Li et al teaches anti-CTLA-4 X anti-PD-1 bispecific antibodies comprising a VH immunoglobulin domain comprising SEQ ID NO:16 or 20 (SEQ ID NO:16 is the same as instant SEQ ID NOs: 87; SEQ ID NO:20 is the same as instant SEQ ID NOs: 121 and 129), a VL immunoglobulin domain comprising SEQ ID NO: 22 (same as instant SEQ ID NOs: 122 and 130) targeting PD-1, and a VH scFv domain comprising SEQ ID NO: 2, 6, or 10 (same as instant SEQ ID NOs: 95, 135, and 133), and a VL scFv domain comprising SEQ ID NO:4, 8, or 12 (same as instant SEQ ID NO: 96, 136, and 134) targeting CTLA-4 ([0044]-[0047], in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the anti-CTLA-4 and anti-PD-1 antibodies are administered as anti-CTLA-4 X anti-PD-1 bispecific antibodies because it is conventional and routine to administer two therapeutic antibodies as a single bispecific reagent.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the anti-CTLA-4 X anti-PD-1 bispecific antibodies of Li et al are substituted in place of the anti-CTLA-4 and anti-PD-1 antibodies of the combined method because the antibodies of the combined method are to treat cancer and Li et al teaches the anti-CTLA-4 X anti-PD-1 bispecific antibodies are to treat cancer. This is an example of s simple substitution of the anti-CTLA-4 X anti-PD-1 bispecific antibodies of Li et al in place of the anti-CTLA-4 and anti-PD-1 antibodies of the combined method with an expectation of success. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
This is a provisional nonstatutory double patenting rejection.
Claims 20-29, 31-34, 36, and 38-42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-7, 9, 11, 12, 15, 17, 20, 25, and 31-39 of copending Application No. 17/640005 in view of in view of Tao et al (Oncology Research, 2017, 25: 1579-1587) and Mimura et al (Fukushima J Med Sci, 2018, 64(2): 46-53) as applied to claims 20-24, 31-34, and 39-42 above, and further in view of Xia et al (US 2022/0275089 A1; 9/1/22).
Teachings of copending claims Tao et al, and Mimura et al are discussed above.
Teachings of copending claims, Tao et al, and Mimura et al do not teach administering the anti-CTLA-4 X anti-PD-1 bispecific antibodies. However, these deficiencies are made up in the teachings of Xia et al.
Xia et al teaches anti-CTLA-4 X anti-PD-1 bispecific antibodies comprising a VH immunoglobulin domain comprising SEQ ID NO:14 or 18 (same as instant SEQ ID NOs: 87 and 129) or a heavy domain comprising SEQ ID NO:40 (same as instant SEQ ID NOs: 82 and 139) and a VL immunoglobulin domain comprising SEQ ID NO: 16 or 20 (same as instant SEQ ID NOs: 88 and 130) or a light chain comprising SEQ ID NO:24 (same as instant SEQ ID NOs:80 and 84) targeting PD-1, and a VH scFv domain comprising SEQ ID NO: 2, 41, 10, 43, or 6 (same as instant SEQ ID NOs: 95, 135, 133, 137, and 131), and a VL scFv domain comprising SEQ ID NO:4, 42, 12, 44, or 8 (same as instant SEQ ID NO: 96, 136, 134, 138, and 132 ) targeting CTLA-4 ([0056]-[0057] and [0103], in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the anti-CTLA-4 and anti-PD-1 antibodies are administered as anti-CTLA-4 X anti-PD-1 bispecific antibodies because it is conventional and routine to administer two therapeutic antibodies as a single bispecific reagent.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the anti-CTLA-4 X anti-PD-1 bispecific antibodies of Xia et al are substituted in place of the anti-CTLA-4 and anti-PD-1 antibodies of the combined method because the antibodies of the combined method are to treat cancer and Xia et al teaches the anti-CTLA-4 X anti-PD-1 bispecific antibodies are to treat cancer. This is an example of s simple substitution of the anti-CTLA-4 X anti-PD-1 bispecific antibodies of Xia et al in place of the anti-CTLA-4 and anti-PD-1 antibodies of the combined method with an expectation of success. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
This is a provisional nonstatutory double patenting rejection.
Claims 20-24, 35, 41, and 42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-7, 9, 11, 12, 15, 17, 20, 25, and 31-39 of copending Application No. 17/640005 in view in view of Feliz-Mosquea et al (Breast Cancer Research and Treatment, 2018, 172: 69-82).
The published copending Application No. 17/640005 is described above as Zhang et al (US 2022/0324971 A1; 10/13/22).
The copending claims and instant claims are drawn to the same anti-CD47 antibodies and methods of administering said antibodies. The copending claims do not specifically recite the antibodies are part of a composition comprising another therapeutic regent or that said composition is administered to a patient. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to therapeutically treat a patient with breast cancer comprising performing the method of Feliz-Mosquea et al wherein the CD47 inhibition therapy is administering the anti-CD47 antibody of the copending claims to the breast cancer patient because the method of Feliz-Mosquea et al treats breast cancer comprising inhibiting CD47 and the anti-CD47 antibody is taught by Zhang et al as an inhibitor of CD47 to be used in breast cancer treatment. This is an example of a simple substitution of one known element for another to obtain predictable results. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
This is a provisional nonstatutory double patenting rejection.
Claims 20-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-7, 9, 11, 12, 15, 17, 20, 25, and 31-39 of copending Application No. 17/640005 in view of in view of Xiong et al (International Journal of Molecular Sciences, 2018, 19(2900): 1-20).
The copending claims and instant claims are drawn to the same anti-CD47 antibodies and methods of administering said antibodies. The copending claims do not specifically recite the antibodies are part of a composition comprising an anti-PD-1/anti-VEGFA bispecific antibody. However, these deficiencies are made up in the teachings of Xiong et al.
Xiong et al teaches a teaches an anti-PD-1/anti-VEGFA bispecific antibody that provides therapeutic benefit to subjects with a solid tumor (Figure 10, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to generate a combination comprising the anti-CD47 antibody of the copending claims and the anti-PD-1/anti-VEGFA bispecific antibody of Xiong et al to treat solid tumors because both reagents have been shown to treat solid tumors. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/SEAN E AEDER/ Primary Examiner, Art Unit 1642
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