DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
1. The Amendment filed January 9, 2026 in response to the Office Action of September 17, 2025, is acknowledged and has been entered. Claims 4, 6, 8-12, 14, 17-22 are now pending. Claims 4, 6, 8-12, 14, 17 are amended. Claims 18-22 are new. Claims 4, 6, 8-12, 14, 17-22 are being examined as drawn to the elected species of:
A. CAPRIN-1 protein SEQ ID NO:2 and SEQ ID NO:31;
B. CAPPRIN-1 monoclonal antibody; and
C. Antibody comprising VH CDRs 1-3 SEQ ID NOs:36-8 and VL CDRs 1-3 SEQ ID NOs:40-42, comprised in VH SEQ ID NO:39 and VL SEQ ID NO:43, respectively.
The claims have been amended to cancel all material drawn to a medicament product, and for all claims to depend from a method of treating cancer.
Claim Objections
2. Claim 17 is objected to because of the following informalities: Claim 17 recites “a method for treating cancer in a subject in need thereof”, followed by administering regents to “a subject”, “wherein the subject has a previous history of cancer treatment.” Examiner suggests the second “a subject” in claim 17 be amended to “the subject” to reference the same subject throughout the claim. Appropriate correction is required.
Maintained Rejections
(amendments addressed)
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.
3. Claim(s) 4, 6, 8-12, 14, and 17-22 remain/are rejected under 35 U.S.C. 103 as being unpatentable over US Patent 9,180,187, Ido et al, issued November 2015; in view of WO 2018/079740, Okano et al, published May 2018 and English Translation; Eisenhauer et al (Gynecologic Oncology, 2014, 134:262-266); and Pignata et al (Annals of Oncology, 2017; 28 (supplement 8); viii51-viii56).
US Patent 9,180,187, Ido recites a claimed method of treating cancer comprising administering to a subject having cancer a medicament comprising an antibody or fragment thereof having immunological reactivity with a CAPRIN-1 protein, and one or two more types of antitumor agents, wherein the antitumor agents are combined together or separately, wherein the cancer expresses the CAPRIN-1 protein on the cell surface of the cancer and the antibody or fragment binds specifically on the extracellular region of a CAPRIN-1 protein existing on the surface of a cancer cell;
wherein the antibody or fragment has immunological reactivity with CAPRIN-1 protein SEQ ID NO:37 in the extracellular region of the CAPRIN-1 protein existing on the surface of a cancer cell, wherein SEQ ID NO:37 is comprised by instant CAPRIN-1 SEQ ID NO:2, and SEQ ID NO:37 comprises a partial amino acid sequence of instant SEQ ID NO:31 (see sequence alignments below);
wherein the one or two more types of antitumor agents comprise gemcitabine and carboplatin;
wherein the antibody and antitumor agents are administered combined together or separately; and
wherein the antibody is human, humanized (monoclonal), chimeric (monoclonal), scFv (monoclonal), or bispecific (claims 1-9).
US Patent 9,180,187, Ido discloses the cancer treated includes breast cancer, brain tumor, leukemia, lymphoma, lung cancer, mastocytoma, renal cancer, uterine cervix cancer, bladder cancer, esophageal cancer, gastric cancer, or colorectal cancer (col. 24, lines 8-45).
Although US Patent 9,180,187, Ido claims and discloses carboplatin and gemcitabine as antitumor agents to be administered in combination with the CAPRIN-1 antibody for the treatment of CAPRIN-1 expressing cancers, Ido does not specifically list the agents directly together.
Ido does not teach the cancer patient treated has ovarian cancer and has a previous history of cancer treatment with a medicament other than CAPRIN-1 antibody + pyrimidine-based drug + carboplatin combined.
Ido does not teach the cancer patient treated has not previously responded to cancer treatment with a medicament other than CAPRIN-1 antibody and a pyrimidine-based drug and carboplatin together or separately, or has not previously responded to treatment with pyrimidine-based drug and/or platinum-containing drug.
Ido does not teach the CAPRIN-1 antibody comprises instant VH and VL SEQ ID NOs:39 and 43, which comprise instant CDR SEQ ID NOs:26-38 and 40-42, respectively.
Okano teaches pharmaceutical compositions comprising CAPRIN-1 monoclonal antibodies that bind CAPRIN-1 expressed on the cell membrane of cancer cells, wherein they bind to instant human CAPRIN-1 sequence SEQ ID NO:2 or 31, and the CAPRIN-1 antibody comprises VH SEQ ID NO:39 and VL SEQ ID NO:43 that are identical to instant SEQ ID NO:39 and 43 (see sequence alignment below) (p. 1, 2, 6, 7, 18, and 32, English Translation). Okano teaches treating cancer expressing CAPRIN-1 by administering the antibody, including treating ovarian cancer, and demonstrates ovarian cancer cells express CAPRIN-1 (p. 4, 17, 18, and 27, English Translation). Okano suggests adding a therapeutic to the CAPRIN-1 antibody to enhance efficacy and antitumor effect of the antibody in cancer treatment (p. 1, 17, and 37, English Translation).
Eisenhauer teaches most ovarian cancer patients relapse after first line therapy with platinum-taxane therapy (Introduction). Recurrent ovarian cancer that relapses more than 6 months after completing primary therapy is considered platinum-sensitive, and re-treatment with platinum combinations has shown the most favorable response in these patients. Preclinical trials and early clinical trials demonstrated synergy between platinum agents and gemcitabine, and activity of this combination has been shown in patients who are platinum-resistant. The positive findings of the gemcitabine carboplatin (GC) doublet in a phase III intergroup study led to its approval by regulatory agencies in several European nations in 2004, and by the U.S. Food and Drug Administration in 2006, for the treatment of platinum-sensitive recurrent ovarian, peritoneal, and tubal cancer (ROC). This study showed a significant improvement in progression-free survival (PFS) for GC compared with C alone (8.6 months versus 5.8 months, respectively), with acceptable toxicity (Introduction).
Eisenhauer demonstrates treating relapsed ovarian cancer patients with a combination of gemcitabine, carboplatin, and a therapeutic antibody, wherein response rate and progression-free survival (PFS) were improved from reported outcomes of the gemcitabine carboplatin doublet (abstract; Results; Figures 1 and 2).
Pignata also teaches that despite optimal surgery and appropriate first-line chemotherapy, 70%–80% of patients with epithelial ovarian cancer will develop disease relapse (abstract). Pignata teaches that 23% of patients relapse during or within 6 months after end of primary chemotherapy and 60% relapse after 6 months (Introduction). With regard to patients relapsed 6 months after primary chemotherapy, Pgnata teaches this subgroup refers to a wide heterogeneous group that include platinum-sensitive (PFI≥12 months) and partially sensitive (PFI≥ 6 <12 months), the use of platinum-based combinations (carboplatin/PLD; carboplatin/ paclitaxel and carboplatin/gemcitabine) is associated to a better outcome (PFS, OS, ORR) compared with non-platinum or platinum single agent treatments (p. viii53, col. 2). Pignata teaches in platinum-sensitive patients, treatment with platinum-based combinations is associated with PFS advantage compared with single agents or non-platinum combinations (abstract).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to make a pharmaceutical composition for treating cancer comprising a CAPRIN-1 antibody, carboplatin, and gemcitabine together. One would have been motivated to, and have a reasonable expectation of success to, because: (1) US Patent 9,180,187, Ido claims and discloses combining carboplatin and gemcitabine with CAPRIN-1 antibody for the treatment of cancer expressing CAPRIN-1; (2) Okano also teaches treating cancer expressing CAPRIN-1 with an CAPRIN-1 antibody, and teaches treating ovarian cancer that is demonstrated to express CAPRIN-1; (3) Okano suggests adding a therapeutic to the CAPRIN-1 antibody to enhance efficacy and antitumor effect of the antibody in cancer treatment; (3) both Eisenhauer and Pignata teach the specific combination of carboplatin and gemcitabine are known and established as a successful combination therapy of ovarian cancer; and (4) Eisenhaur teaches and demonstrate therapy of ovarian cancer with carboplatin and gemcitabine can be improved further by adding a therapeutic antibody.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to treat ovarian cancer patients with the combination of CAPRIN-1 antibody + gemcitabine + carboplatin that: i) are relapsed, previously treated with platinum-based therapy, ii) have not previously responded to cancer treatment with a medicament other than CAPRIN-1 antibody and a pyrimidine-based drug and carboplatin together or separately, or iii) have not previously responded to treatment with pyrimidine-based drug and/or platinum-containing drug. One would have been motivated to, and have a reasonable expectation of success to, because: (1) US Patent 9,180,187, Ido claims and discloses combining carboplatin and gemcitabine with CAPRIN-1 antibody for the treatment of cancer expressing CAPRIN-1 regardless of prior treatment history; (2) Okano also teaches treating cancer expressing CAPRIN-1 with an CAPRIN-1 antibody, and teaches treating ovarian cancer that is demonstrated to express CAPRIN-1; (3) Okano suggests adding a therapeutic to the CAPRIN-1 antibody to enhance efficacy and antitumor effect of the antibody in cancer treatment; (3) both Eisenhauer and Pignata teach the specific combination of carboplatin and gemcitabine is known and established as a superior combination therapy of ovarian cancer that is relapsed after platinum-based therapy; and (4) Eisenhaur teaches and demonstrates therapy of relapsed ovarian cancer with carboplatin and gemcitabine can be improved further by adding a therapeutic antibody.
Ido and Okano recognize the need in the art to treat CAPRIN-1-expressing tumors with CAPRIN-1 antibody and suggest adding anticancer therapeutics to enhance efficacy. Given the recognized need to treat CAPRIN-1-expressing tumors with CAPRIN-1 antibody and anticancer therapeutics, given the known function of the CAPRIN-1 antibody treating CAPRIN-1-expressing tumors including ovarian cancer, the known success demonstrated by Eisenhauer and Pignata for treatment of ovarian cancer with the specific combination of carboplatin and gemcitabine, the known success for the specific combination of carboplatin and gemcitabine to treat relapsed ovarian cancers, and the demonstrated success of improving treatment of relapsed ovarian cancer by adding a tumor-targeting therapeutic antibody to the carboplatin and gemcitabine regimen, one of skill in the art could have pursued administering the anti-CAPRIN-1 antibody + carboplatin + gemcitabine to treat ovarian cancer patients that i) are relapsed, previously treated with platinum-based therapy, ii) have not previously responded to cancer treatment with a medicament other than CAPRIN-1 antibody and a pyrimidine-based drug and carboplatin together or separately, or iii) have not previously responded to treatment with pyrimidine-based drug and/or platinum-containing drug, with a reasonable expectation of success.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to utilize CAPRIN-1 antibody taught by Okano in the composition and method of the combine references cited above. One would have been motivated to, and have a reasonable expectation of success to, because: (1) US Patent 9,180,187, Ido claims and discloses combining carboplatin and gemcitabine with CAPRIN-1 antibody for the treatment of cancer expressing CAPRIN-1; (2) Okano also teaches treating cancer expressing CAPRIN-1 with an CAPRIN-1 antibody; and (3) Okano teaches the known sequence of CAPRIN-1 therapeutic antibodies encompass VH and VL SEQ ID NOs:39 and 43.
Instant SEQ ID NO:2 (Qy) aligned with US Patent 9,180,187 SEQ ID NO:37 (Db):
RESULT 1
AASEQ2_09122025_091616
Query Match 8.3%; Score 306; DB 1; Length 58;
Best Local Similarity 100.0%;
Matches 58; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 240 VFQSNYFDSTHNHQNGLCEEEEAASAPAVEDQVPEAEPEPAEEYTEQSEVESTEYVNR 297
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 VFQSNYFDSTHNHQNGLCEEEEAASAPAVEDQVPEAEPEPAEEYTEQSEVESTEYVNR 58
Instant SEQ ID NO:31 (Qy) aligned with US Patent 9,180,187 SEQ ID NO:37 (Db):
RESULT 1
AASEQ2_09122025_092530
Query Match 26.6%; Score 86; DB 1; Length 58;
Best Local Similarity 100.0%;
Matches 17; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EEYTEQSEVESTEYVNR 17
|||||||||||||||||
Db 42 EEYTEQSEVESTEYVNR 58
Instant heavy chain variable region SEQ ID NO:39 aligned with WO 2018/079740, Okano, SEQ ID NO:39:
BFF89849
ID BFF89849 standard; protein; 128 AA.
XX
AC BFF89849;
XX
DT 14-JUN-2018 (first entry)
XX
DE Anti-CAPRIN-1 antibody VH region, SEQ ID 39.
XX
KW Caprin 1; Cytopasmic-activation and proliferation-associated protein 1;
KW antibody; antibody therapy; cancer; cytostatic;
KW heavy chain variable region; immunoconjugate; prophylactic to disease;
KW therapeutic.
XX
OS Gallus gallus.
XX
CC PN WO2018079740-A1.
XX
CC PD 03-MAY-2018.
XX
CC PF 27-OCT-2017; 2017WO-JP038986.
XX
PR 28-OCT-2016; 2016JP-00211376.
XX
CC PA (TORA ) TORAY IND INC.
XX
CC PI Okano F, Saito T;
XX
DR WPI; 2018-34158C/33.
XX
CC PT New conjugate used in pharmaceutical composition for preventing and/or
CC PT treating cancer e.g. brain tumor, obtained by antibody or its fragment
CC PT immunologically reactive with cell cycle associated protein-1 and immune
CC PT activation factor.
XX
CC PS Claim 5; SEQ ID NO 39; 102pp; Japanese.
XX
CC The present invention relates to a novel conjugate, useful in a
CC pharmaceutical composition for preventing and/or treating cancer. The
CC conjugate is obtained by linking an antibody, or its fragment, that is
CC immunologically responsive to cytopasmic-activation and proliferation-
CC associated protein 1 (CAPRIN-1) protein to an immune activation factor.
CC The invention also provides a method for preventing and/or treating
CC cancer. The cancer is breast cancer, kidney cancer, pancreatic cancer,
CC colon cancer, lung cancer, brain tumor, stomach cancer, uterine cancer,
CC ovarian cancer, prostate cancer, bladder cancer, esophageal cancer,
CC leukemia, lymphoma, liver cancer, gall bladder cancer, sarcoma,
CC mastocytoma, melanoma, adrenal cortical cancer, Ewing's tumor, Hodgkin's
CC lymphoma, mesothelioma, multiple myeloma, head and neck cancer,
CC testicular cancer, and thyroid cancer. The present sequence is an anti-
CC CAPRIN-1 antibody heavy chain variable region (VH), where the antibody is
CC used in the conjugate of the invention for treating the above mentioned
CC diseases.
XX
SQ Sequence 128 AA;
ALIGNMENT:
Query Match 100.0%; Score 681; Length 128;
Best Local Similarity 100.0%;
Matches 128; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AVTLDESGGGLQMSRGGLSLVCKASGFDFSSYQMNWIRQAPGKGLEFVAAINKFGNSTGH 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AVTLDESGGGLQMSRGGLSLVCKASGFDFSSYQMNWIRQAPGKGLEFVAAINKFGNSTGH 60
Qy 61 GAAVKGRVTISRDNGQSTVRLQLNNLRAEDTAIYFCTKHAYGYCGSGTWCAAGEIDAWGH120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GAAVKGRVTISRDNGQSTVRLQLNNLRAEDTAIYFCTKHAYGYCGSGTWCAAGEIDAWGH120
Qy 121 GTEVIVSS 128
||||||||
Db 121 GTEVIVSS 128
Instant light chain variable region SEQ ID NO:43 aligned with WO 2018/079740, Okano, SEQ ID NO:43:
BFF89853
ID BFF89853 standard; protein; 108 AA.
XX
AC BFF89853;
XX
DT 14-JUN-2018 (first entry)
XX
DE Anti-CAPRIN-1 antibody VL region, SEQ ID 43.
XX
KW Caprin 1; Cytopasmic-activation and proliferation-associated protein 1;
KW antibody; antibody therapy; cancer; cytostatic; immunoconjugate;
KW light chain variable region; prophylactic to disease; therapeutic.
XX
OS Gallus gallus.
XX
CC PN WO2018079740-A1.
XX
CC PD 03-MAY-2018.
XX
CC PF 27-OCT-2017; 2017WO-JP038986.
XX
PR 28-OCT-2016; 2016JP-00211376.
XX
CC PA (TORA ) TORAY IND INC.
XX
CC PI Okano F, Saito T;
XX
DR WPI; 2018-34158C/33.
XX
CC PT New conjugate used in pharmaceutical composition for preventing and/or
CC PT treating cancer e.g. brain tumor, obtained by antibody or its fragment
CC PT immunologically reactive with cell cycle associated protein-1 and immune
CC PT activation factor.
XX
CC PS Claim 5; SEQ ID NO 43; 102pp; Japanese.
XX
CC The present invention relates to a novel conjugate, useful in a
CC pharmaceutical composition for preventing and/or treating cancer. The
CC conjugate is obtained by linking an antibody, or its fragment, that is
CC immunologically responsive to cytopasmic-activation and proliferation-
CC associated protein 1 (CAPRIN-1) protein to an immune activation factor.
CC The invention also provides a method for preventing and/or treating
CC cancer. The cancer is breast cancer, kidney cancer, pancreatic cancer,
CC colon cancer, lung cancer, brain tumor, stomach cancer, uterine cancer,
CC ovarian cancer, prostate cancer, bladder cancer, esophageal cancer,
CC leukemia, lymphoma, liver cancer, gall bladder cancer, sarcoma,
CC mastocytoma, melanoma, adrenal cortical cancer, Ewing's tumor, Hodgkin's
CC lymphoma, mesothelioma, multiple myeloma, head and neck cancer,
CC testicular cancer, and thyroid cancer. The present sequence is an anti-
CC CAPRIN-1 antibody light chain variable region (VL), where the antibody is
CC used in the conjugate of the invention for treating the above mentioned
CC diseases.
XX
SQ Sequence 108 AA;
ALIGNMENT:
Query Match 100.0%; Score 564; Length 108;
Best Local Similarity 100.0%;
Matches 108; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QAASTQPSSVSANPGETVEITCSGGGSYSYGWFQQKSPGSAPVTVIYYNNKRPSDIPSRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QAASTQPSSVSANPGETVEITCSGGGSYSYGWFQQKSPGSAPVTVIYYNNKRPSDIPSRF 60
Qy 61 SGSKSGSTGTLTITGVQADDEAVYYCGSGDSTDTAVFGAGTTLTVLGQ 108
||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGSKSGSTGTLTITGVQADDEAVYYCGSGDSTDTAVFGAGTTLTVLGQ 108
4. Claim(s) 4, 6, 8-12, 14, and 17-22 remain/are rejected under 35 U.S.C. 103 as being unpatentable over US Patent 9,428,581, Saito et al, issued August 2016; in view of Suresh et al (2007, Journal of Clinical Oncology, 25; number 18, suppl, abstract 15102).
Saito claims and discloses a method of treating CAPRIN-1 expressing gallbladder cancer, comprising: administering a pharmaceutical composition to a subject having CAPRIN-1 expressing gallbladder cancer, said pharmaceutical composition comprising, as an active ingredient, an antibody or a fragment thereof having immunological reactivity with a CAPRIN-1 protein expressed on the surface of a gallbladder tumor cell that comprises the amino acid sequence SEQ ID NOs: 2 (identical to instant SEQ ID NO:2) (claim 1), wherein the antibody is monoclonal (claim 4 and 10), wherein the antibody is humanized, chimeric, scFv, multispecific (claim 5 and 12), wherein the CAPRIN-1 antibody comprises CDR SEQ ID NOs:37-39 and 41-43, that are identical to instant CDR SEQ ID NOs:36-38 and 40-42, respectively (claims 6, 15, 16, 17, 18); wherein the pharmaceutical composition further comprises an antitumor agent (claim 8).
Saito discloses that antitumor agents encompass gemcitabine and carboplatin (col. 18, line 59 to col. 19, line 40), and antitumor agents and antibody can be administered simultaneously or separately to the subject (col. 33, lines 3-27). Saito discloses the VH and VL for the CARPIN-1 antibody comprising CDR SEQ ID NOs: 37-39 and 41-43 comprise SEQ ID NOs:40 and 44 that are identical to instant SEQ ID NOs:39 and 43, respectively (see sequence searches below) (col. 21, lines 49-59). Saito discloses the CAPRIn-1 antibody binds to CAPRIN-1 fragment SEQ ID NO:266 that sis100% identical to instant SEQ ID NO:31 (col. 2, lines 30-39; col. 8, lines 33-65; col. 10, lines 3-16; Example 7).
Saito does not specifically select gemcitabine and carboplatin for combination with CAPRIN-1 antibody, and does not teach treating gallbladder patients previously treated with therapy lacking CAPRIN-1 antibody + pyrimidine-based drug + carboplatin with the combination of CAPRIN-1 antibody + gemcitabine + carboplatin.
Saito does not teach the cancer patient treated has not previously responded to cancer treatment with a medicament other than CAPRIN-1 antibody and a pyrimidine-based drug and carboplatin together or separately, or has not previously responded to treatment with pyrimidine-based drug and/or platinum-containing drug.
Suresh teaches successfully treating gallbladder patients clinically with a combination of gemcitabine and carboplatin, wherein 29.2% of patients achieved complete or partial responses, and 50% achieved stable disease. Suresh teaches it is known that gemcitabine is synergistic with platinum compounds.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to combine gemcitabine and carboplatin with the pharmaceutical composition for the treatment of gallbladder cancer taught and claimed by Saito. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Saito suggests adding antitumor agents to their CAPRIN-1 antibody pharmaceutical composition for treatment of gallbladder cancer; (2) Suresh discloses that gemcitabine and carboplatin are known antitumor agents that successfully treat gallbladder cancer; and (3) Suresh teaches it is known that the combination of gemcitabine with carboplatin is synergistic in the treatment of cancer.
Those of skill in the art recognize that the gallbladder cancer therapeutic agents, CAPRIN-1 antibody, gemcitabine, and carboplatin, all taught or known to treat gallbladder cancer, could have been combined by known methods, and that in combination, each agent of the composition merely would have performed the same function as they did separately, and one of ordinary skill in the art would have recognized that the results of the combination would predictably treat gallbladder cancer.
As stated in the above rejection, each of these agents had been taught by the prior art to be used in treatment of gallbladder cancer, thus the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose. In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As this court explained in Crockett, the idea of combining them flows logically from their having been individually taught in the prior art.” In the instant case, it is prima facie obvious to combine the three agents, each of which is taught by the prior art to be useful for the same purpose, in order to form a third therapeutic composition which is to be used for the very same purpose of treating gallbladder cancer. See MPEP 2144.06.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to treat gallbladder cancer patients with the combination of CAPRIN-1 antibody + gemcitabine + carboplatin that: i) are relapsed, previously treated with platinum-based therapy, ii) have not previously responded to cancer treatment with a medicament other than CAPRIN-1 antibody and a pyrimidine-based drug and carboplatin together or separately, or iii) have not previously responded to treatment with pyrimidine-based drug and/or platinum-containing drug. One would have been motivated to, and have a reasonable expectation of success to, because: Saito and Suresh both teach identifying gallbladder patients as in need of cancer treatment, regardless of prior therapies. One of ordinary skill in the art would have a reasonable expectation of success treating gallbladder patient having prior therapy and not responding to prior therapies, given the prior art teaches or demonstrates successful treatment of gall bladder cancer with these agents regardless of prior therapeutic history.
Instant SEQ ID NO:39 aligned with Saito SEQ ID NO:40:
US-14-389-078A-40
Filing date in PALM: 2014-09-29
Sequence 40, US/14389078A
Patent No. 9428581
GENERAL INFORMATION
APPLICANT: TORAY INDUSTRIES, INC.
APPLICANT: SAITO, Takanori et al.
TITLE OF INVENTION: PHARMACEUTICAL COMPOSITION FOR TREATMENT AND/OR PREVENTION OF
TITLE OF INVENTION: GALL BLADDER CANCER
FILE REFERENCE: 1254-0565PUS1
CURRENT APPLICATION NUMBER: US/14/389,078A
CURRENT FILING DATE: 2014-09-29
PRIOR APPLICATION NUMBER: PCT/JP2013/059569
PRIOR FILING DATE: 2013-03-29
PRIOR APPLICATION NUMBER: JP 2012-080780
PRIOR FILING DATE: 2012-03-30
NUMBER OF SEQ ID NOS: 432
SEQ ID NO 40
LENGTH: 128
ALIGNMENT:
Query Match 100.0%; Score 681; Length 128;
Best Local Similarity 100.0%;
Matches 128; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AVTLDESGGGLQMSRGGLSLVCKASGFDFSSYQMNWIRQAPGKGLEFVAAINKFGNSTGH 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AVTLDESGGGLQMSRGGLSLVCKASGFDFSSYQMNWIRQAPGKGLEFVAAINKFGNSTGH 60
Qy 61 GAAVKGRVTISRDNGQSTVRLQLNNLRAEDTAIYFCTKHAYGYCGSGTWCAAGEIDAWGH120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GAAVKGRVTISRDNGQSTVRLQLNNLRAEDTAIYFCTKHAYGYCGSGTWCAAGEIDAWGH120
Qy 121 GTEVIVSS 128
||||||||
Db 121 GTEVIVSS 128
Instant SEQ ID NO:43 aligned with Saito SEQ ID NO:44:
US-14-389-078A-44
Filing date in PALM: 2014-09-29
Sequence 44, US/14389078A
Patent No. 9428581
GENERAL INFORMATION
APPLICANT: TORAY INDUSTRIES, INC.
APPLICANT: SAITO, Takanori et al.
TITLE OF INVENTION: PHARMACEUTICAL COMPOSITION FOR TREATMENT AND/OR PREVENTION OF
TITLE OF INVENTION: GALL BLADDER CANCER
FILE REFERENCE: 1254-0565PUS1
CURRENT APPLICATION NUMBER: US/14/389,078A
CURRENT FILING DATE: 2014-09-29
PRIOR APPLICATION NUMBER: PCT/JP2013/059569
PRIOR FILING DATE: 2013-03-29
PRIOR APPLICATION NUMBER: JP 2012-080780
PRIOR FILING DATE: 2012-03-30
NUMBER OF SEQ ID NOS: 432
SEQ ID NO 44
LENGTH: 108
ALIGNMENT:
Query Match 100.0%; Score 564; Length 108;
Best Local Similarity 100.0%;
Matches 108; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QAASTQPSSVSANPGETVEITCSGGGSYSYGWFQQKSPGSAPVTVIYYNNKRPSDIPSRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QAASTQPSSVSANPGETVEITCSGGGSYSYGWFQQKSPGSAPVTVIYYNNKRPSDIPSRF 60
Qy 61 SGSKSGSTGTLTITGVQADDEAVYYCGSGDSTDTAVFGAGTTLTVLGQ 108
||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGSKSGSTGTLTITGVQADDEAVYYCGSGDSTDTAVFGAGTTLTVLGQ 108
5. Claim(s) 4, 6, 8-12, 14, and 17-22 remain/are rejected under 35 U.S.C. 103 as being unpatentable over US Patent 9,416,193, Saito et al, issued August 2016; in view of Azmy et al (International Scholarly Research Notices, 2012, article 420931).
Saito claims a method of treating liver cancer in a subject, comprising administering a pharmaceutical composition comprising as an active ingredient a CAPRIN-1 antibody or fragment thereof having immunological reactivity with CAPRIN-1 amino acid sequence SEQ ID NO:2, wherein the cancer is a CAPRIN-1 expressing liver cancer, and the antibody binds to CAPRIN-1 expressed on the surface of the liver tumor cell (claim 1), wherein the antibody monoclonal (claim 4), wherein the antibody is humanized, chimeric, scFv, or multispecific (claim 5), wherein the CAPRIN-1 antibody comprises CDR SEQ ID NOs:37-39 and 41-43 (claim 6); wherein the antibody composition further comprises an antitumor agent (claim 8).
Saito further discloses the antibody comprising CDR SEQ ID NOs: 37-39 and 41-43 comprises VH and VL SEQ ID NOs:40 and 44 that are identical to instant SEQ ID NO:39 and 43, respectively (col. 15-16). The antibody can bind to CARPIN-1 protein fragment SEQ ID NO:266 that is identical to instant SEQ ID NO:31 (col. 8, lines 21-42) Antitumor agents encompass gemcitabine and carboplatin (col. 18, line 33 to col. 19, line 14), and antitumor agents and antibody can be administered simultaneously or separately to the subject (col. 32, lines 12-35). Liver cancer includes hepatocellular cancer (col. 31, lines 10-14).
Saito does not specifically select gemcitabine and carboplatin for combination with CAPRIN-1 antibody, and does not teach treating liver cancer patients previously treated with therapy lacking CAPRIN-1 antibody + pyrimidine-based drug + carboplatin with the combination of CAPRIN-1 antibody + gemcitabine + carboplatin.
Saito does not teach the cancer patient treated has not previously responded to cancer treatment with a medicament other than CAPRIN-1 antibody and a pyrimidine-based drug and carboplatin together or separately, or has not previously responded to treatment with pyrimidine-based drug and/or platinum-containing drug.
Azmy teaches effectively treating hepatocellular liver cancer with a combination of carboplatin and gemcitabine, wherein the patients were previously treated with surgery, TACE, or radiofrequency ablation that does not include CAPRIN-1 antibody, gemcitabine and carboplatin (abstract; Table 1).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to combine gemcitabine and carboplatin with the pharmaceutical composition for the treatment of liver cancer taught and claimed by Saito. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Saito suggests adding antitumor agents to their CAPRIN-1 antibody pharmaceutical composition for treatment of liver cancer; and (2) Azmy discloses that gemcitabine and carboplatin are known antitumor agents that successfully treat liver cancer.
Those of skill in the art recognize that the liver cancer therapeutic agents, CAPRIN-1 antibody, gemcitabine, and carboplatin, all taught or known to treat liver cancer, could have been combined by known methods, and that in combination, each agent of the composition merely would have performed the same function as they did separately, and one of ordinary skill in the art would have recognized that the results of the combination would predictably treat liver cancer.
As stated in the above rejection, each of these agents had been taught by the prior art to be used in treatment of gallbladder cancer, thus the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose. In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As this court explained in Crockett, the idea of combining them flows logically from their having been individually taught in the prior art.” In the instant case, it is prima facie obvious to combine the three agents, each of which is taught by the prior art to be useful for the same purpose, in order to form a third therapeutic composition which is to be used for the very same purpose of treating liver cancer. See MPEP 2144.06.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to liver cancer patients in the method of Saito that were previously treated with a therapy that did not comprise CAPRIN-1 antibody + gemcitabine + carboplatin.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to treat liver cancer patients with the combination of CAPRIN-1 antibody + gemcitabine + carboplatin that: i) are relapsed, previously treated with platinum-based therapy, ii) have not previously responded to cancer treatment with a medicament other than CAPRIN-1 antibody and a pyrimidine-based drug and carboplatin together or separately, or iii) have not previously responded to treatment with pyrimidine-based drug and/or platinum-containing drug. One would have been motivated to, and have a reasonable expectation of success to, because Saito and Azmy both teach identifying liver patients as in need of cancer treatment, regardless of prior therapy and not responding to prior therapies, and Azmy demonstrates carboplatin and gemcitabine successfully treat patients having previous treatment that excluded CAPRIN-1 antibody + gemcitabine + carboplatin.
Response to 35 USC 103 Arguments
6. Applicants present the Okano declaration under 37 CFR 1.132 and argue that they demonstrate combined therapy with anti-CAPRIN-1 antibody TRK-950 and gemcitabine/carboplatin for breast cancer xenografts in mice resulted in “much stronger antitumor effect” compared to the administration of the anti-CAPRIN-1 alone, or administration of the gemcitabine/carboplatin combination (Figure 1). Applicants argue that the cited references, Saito and Ido, fail to demonstrate the synergistic effects of the combined therapy of TRK-950, gemcitabine, and carboplatin. Applicants argue that their data demonstrates synergistic and unexpected superior results.
Applicants argue that as shown in Example 2 of the present specification, an ovarian cancer patient was given a combination of standard gemcitabine and carboplatin combination therapy and "TRK-950" (anti- CAPRIN-1 antibody under clinical trial as a therapeutic agent for cancer) at a dose of 10 mg/kg. As a result of evaluation of the tumor sizes of left supraclavicular node and hepatic periportal node, as target lesions, having metastatic foci by CT examination, the total tumor size was reduced by approximately 33% approximately 1 month after the start of administration and partial response was obtained. As a result of continuous administration, the total tumor size was reduced by approximately 42% approximately 3 months after the start of administration. Further, the tumor in the hepatic periportal node completely disappeared approximately 5 months after the start of administration, and the total tumor size was reduced by approximately 81%. The level of a tumor marker CA125 (reference: 25 U/mL) in peripheral blood, which was 180.2 U/mL before the start of administration, was decreased to 25.0 U/mL or lower approximately 100 days after the start of administration.
Applicants argue that the cited prior art does not provide an expectation of synergy or superior efficacy of cancer treatment by combining anti-CAPRIN-1 antibody with gemcitabine and carboplatin, and the instant specification and declaration provide evidence of non-obviousness.
7. The arguments and declaration have been carefully considered but are not persuasive. The data presented in the Okano declaration and specification at Example 2 are directed to treatment with a specific anti-CAPRIN-1 antibody “TRK-950” and carboplatin + gemcitabine. Applicants are arguing the synergistic results or superior therapeutic efficacy for methods combining gemcitabine and carboplatin with anti-CAPRIN-1 antibody “TRK-950”. However, the instant claims do not recite administering any anti-CAPRIN-1 antibody “TRK-950”. The unexpected or superior results argued by Applicants are for a method that is not commensurate in scope with the instantly claimed method. MPEP 716.02(d) states:
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range.
In the instant case, the Okano declaration and Example 2 of the specification fail to demonstrate an expected synergy or superior therapeutic efficacy to be achieved by the addition of any all anti-CAPRIN-1 antibodies to carboplatin/gemcitabine treatment as broadly claimed. The data provided by Applicants does not provide any predictable extrapolation of results for the “TRK-950” antibody to all anti-CAPRIN-1 antibody combinations with carboplatin/gemcitabine and for the treatment of all cancers broadly encompassed by the claims. Applicant’s showing of unexpected results for “TRK-950” antibody is not demonstrated to occur over the entire claimed range of anti-CAPRIN-1 antibodies and cancers, and is not persuasive.
The cited prior art provides motivation and a reasonable expectation of success to treat the claimed cancers with anti-CAPRIN-1 antibody and in combination with established/known anti-cancer combination gemcitabine/carboplatin for the reasons of record.
8. Applicants point to an article by Campione et al (2016) and argue this article demonstrates combining rituximab with imiquimod was ineffective. Applicants argue this is evidence supporting the unpredictability of combining therapies to result in improved efficacy or synergistic effects.
9. The arguments have been considered but are not persuasive. Campione does not appear to be related to treatment of cancer with anti-CAPRIN-1 antibody combined with gemcitabine and carboplatin, therefore does not provide persuasive evidence that such combinations would be unpredictable for the treatment of cancer.
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.
10. Claims 4, 6, 8-12, 14, and 17-22 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 7, and 9 of U.S. Patent No. 9,180,187 in view of WO 2018/079740, Okano et al, published May 2018 and English Translation; Eisenhauer et al (Gynecologic Oncology, 2014, 134:262-266); and Pignata et al (Annals of Oncology, 2017; 28 (supplement 8); viii51-viii56).
The US Patent claims (bold emphasis added):
1. A method for treating and/or preventing recurrence of a CAPRIN-1 expressing cancer, comprising:
administering a medicament to a subject suspected of having a cancer,
wherein the medicament comprises a combination of an antibody or a fragment thereof having immunological reactivity with a CAPRIN-1 protein, and one or two or more types of antitumor agents,
wherein the antibody or fragment and the antitumor agent or antitumor agents are combined together or separately,
wherein the antibody or fragment and the antitumor agent are not conjugated together,
wherein the cancer expresses the CAPRIN-1 protein on the cell surface of the cancer and the antibody or fragment binds specifically to the extracellular region of a CAPRIN-1 protein existing on the surface of a cancer cell.
2. The method according to claim 1, wherein the antibody or a fragment thereof having immunological reactivity with a CAPRIN-1 protein is an antibody or a fragment thereof which binds specifically to a polypeptide consisting of the amino acid sequence of SEQ ID NO: 37 in the extracellular region of the CAPRIN-1 protein existing on the surface of a cancer cell.
3. The method according to claim 1, wherein the CAPRIN-1 protein is from a human.
4. The method according to claim 1, wherein the above antitumor agent is selected from one or more of the group consisting of: paclitaxel, doxorubicin, daunorubicin, cyclophosphamide, methotrexate, 5-fluorouracil, thiotepa, busulfan, improsulfan, piposulfan, benzodopa, carboquone, meturedopa, uredopa, altretamine, triethylenemelamine, triethylenephosphoramide, triethilenethiophosphoramide, trimethylolomelamine, bullatacin, bullatacinone, camptothecin, bryostatin, callystatin, cryptophycinl, cryptophycin8, dolastatin, duocarmycin, eleutherobin, pancratistatin, sarcodictyin, spongistatin, chlorambucil, chlornaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard, carmustine, chlorozotocin, fotemustine, lomustine, nimustine, ranimustine, calicheamicin, dynemicin, clodronate, esperamicin, aclacinomycin, actinomycin, authramycin, azaserine, bleomycin, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycin, dactinomycin, detorbicin, 6-diazo-5-oxo-L-norleucine, adriamycin, epirubicin, esorubicin, idarubicin, marcellomycin, mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin, denopterin, pteropterin, trimetrexate, fludarabine, 6-mercaptopurine, thiamiprine, thioguanine, ancitabine, azacitidine, 6-azauridine (azauridine), carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine, calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone, aminoglutethimide, mitotane, trilostane, frolinic acid, aceglatone, aldophosphamideglycoside, aminolaevulinic acid, eniluracil, amsacrine, bestrabucil, bisantrene, edatraxate, defofamine, demecolcine, diaziquone, elfornithine, elliptinium acetate (elliptinium), epothilone, etoglucid, lenthinan, lonidamine, maytansine, ansamitocine, mitoguazone, mitoxantrone, mopidanmol, nitraerine, pentostatin, phenamet, pirarubicin, losoxantrone, podophyllinic acid, 2-ethyl hydrazide, procarbazine, razoxane, rhizoxin, schizophyllan, spirogermanium, tenuazonic acid, triaziquone, roridine A, anguidine, urethane, vindesine, dacarbazine, mannomustine, mitobronitol, mitolactol, pipobroman, gacytosine, docetaxel, chlorambucil, gemcitabine, 6-thioguanine, mercaptopurine, cisplatin, oxaliplatin, carboplatin, vinblastine, etoposide, ifosfamide, mitoxanthrone, vincristine, vinorelbine, novantrone, teniposide, edatrexate, daunomycin, aminopterin, xeloda, ibandronate, irinotecan, topoisomerase inhibitor, difluoromethylolnitine (DMFO), retinoic acid, capecitabine, and pharmaceutically acceptable salts and derivatives thereof.
6. The method according to claim 1, wherein the antibody is selected from the group consisting of single chain antibodies (scFv), Fab, F(ab′)2, and Fv.
7. The method according to claim 1, wherein the antibody is a human antibody, humanized antibody, chimeric antibody, single chain antibody, or bispecific antibody.
9. A method for treating and/or preventing recurrence of a CAPRIN-1 expressing cancer, comprising
administering a medicament to a subject suspected of having a cancer,
wherein the medicament comprises a combination of an antibody or a fragment thereof having immunological reactivity with a CAPRIN-1 protein, and one or two or more types of antitumor agents,
wherein the antibody or fragment and the antitumor agent or antitumor agents are combined together or separately,
wherein the antibody or fragment and the antitumor agent are not conjugated together,
wherein the cancer expresses the CAPRIN-1 protein on the cell surface of the cancer, and
wherein the antibody or a fragment thereof having immunological reactivity with a CAPRIN-1 protein is an antibody or a fragment thereof which binds specifically to a polypeptide consisting of the amino acid sequence of SEQ ID NO: 37 in the extracellular region of the CAPRIN-1 protein existing on the surface of a cancer cell.
(A) The US Patent claims but does not select specifically carboplatin and gemcitabine combined together with CAPRIN-1 antibody as the medicament.
(B) The US Patent does not claim the cancer patient treated has ovarian cancer that: i) is relapsed, previously treated with platinum-based therapy, ii) has not previously responded to cancer treatment with a medicament other than CAPRIN-1 antibody and a pyrimidine-based drug and carboplatin together or separately, or iii) has not previously responded to treatment with pyrimidine-based drug and/or platinum-containing drug.
(C) The US Patent does not teach the CAPRIN-1 antibody comprises instant VH and VL SEQ ID NOs:39 and 43, which comprise instant CDR SEQ ID NOs:26-38 and 40-42, respectively.
Okano, Eisenhauer, and Pignata teach as set forth above.
Elements (A)-(C) listed above are rendered obvious in the patented claims by Okano, Eisenhauer, and Pignata, for the reasons stated in the rejection under 35 U.S.C. 103 above.
11. Claims 4, 6, 8-12, 14, and 17-22 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,428,581 in view of WO 2018/079740, Okano et al, published May 2018 and English Translation; and Suresh et al (2007, Journal of Clinical Oncology, 25; number 18, suppl, abstract 15102).
The US Patent claims a method of treating CAPRIN-1 expressing gallbladder cancer, comprising: administering a pharmaceutical composition to a subject having CAPRIN-1 expressing gallbladder cancer, said pharmaceutical composition comprising, as an active ingredient, an antibody or a fragment thereof having immunological reactivity with a CAPRIN-1 protein expressed on the surface of a gallbladder tumor cell that comprises the amino acid sequence SEQ ID NOs: 2 (identical to instant SEQ ID NO:2) (claim 1), wherein the antibody is monoclonal (claim 4 and 10), wherein the antibody is humanized, chimeric, scFv, multispecific (claim 5 and 12), wherein the CAPRIN-1 antibody comprises CDR SEQ ID NOs:37-39 and 41-43, that are identical to instant CDR SEQ ID NOs:36-38 and 40-42, respectively (claims 6, 15, 16, 17, 18); wherein the pharmaceutical composition further comprises an antitumor agent (claim 8).
The US Patent does not claim the antitumor agents combined with CAPRIN-1 antibody for gallbladder cancer treatment are gemcitabine and carboplatin. The US Patent does not claim the gallbladder cancer: i) is relapsed, previously treated with platinum-based therapy, ii) has not previously responded to cancer treatment with a medicament other than CAPRIN-1 antibody and a pyrimidine-based drug and carboplatin together or separately, or iii) has not previously responded to treatment with pyrimidine-based drug and/or platinum-containing drug. The US Patent does not claim the CAPRIN-1 antibody comprising CDR SEQ ID NOs:37-39 and 41-43 comprise VH and VL instant SEQ ID NOs:39 and 43.
Suresh teaches as set forth above and renders obvious the addition of gemcitabine and carboplatin to the composition claimed by the US Patent for the reasons set forth above. Suresh renders obvious treating previously treated and refractory gallbladder cancer patients for the reasons set forth above.
Okano teaches the known VH and VL sequences of SEQ ID NOs:39 and 43 that comprise the CDR SEQ ID NOs:37-39 and 41-43 of the CAPRIN-1 antibody claimed by the US Patent. Okano also teaches treating gallbladder cancer with the CAPRIN-1 antibody.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to utilize the CAPRIN-1 antibody taught by Okano in the composition of the US Patent. One would have been motivated to, and have a reasonable expectation of success to, because Okano teaches the complete VH and VL sequence of an antibody comprising the CDR sequences of the CAPRIN-1 antibody claimed by the US Patent, and teaches using it for the same purpose as the US Patent.
12. Claims 4, 6, 8-12, 14, and 17-22 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,416,193 in view of WO 2018/079740, Okano et al, published May 2018 and English Translation; and Azmy et al (International Scholarly Research Notices, 2012, article 420931).
The US Patent claims a method of treating CAPRIN-1 expressing liver cancer, comprising: administering a pharmaceutical composition to a subject having CAPRIN-1 expressing liver cancer, said pharmaceutical composition comprising, as an active ingredient, an antibody or a fragment thereof having immunological reactivity with a CAPRIN-1 protein expressed on the surface of a gallbladder tumor cell that comprises the amino acid sequence SEQ ID NOs: 2 (identical to instant SEQ ID NO:2); wherein the antibody is monoclonal; wherein the antibody is humanized, chimeric, scFv, multispecific; wherein the CAPRIN-1 antibody comprises CDR SEQ ID NOs:37-39 and 41-43, that are identical to instant CDR SEQ ID NOs:36-38 and 40-42, respectively; wherein the pharmaceutical composition further comprises an antitumor agent, as set forth above.
The US Patent does not claim the antitumor agents combined with CAPRIN-1 antibody for liver cancer treatment are gemcitabine and carboplatin. The US Patent does not claim the liver cancer: i) is relapsed, previously treated with platinum-based therapy, ii) has not previously responded to cancer treatment with a medicament other than CAPRIN-1 antibody and a pyrimidine-based drug and carboplatin together or separately, or iii) has not previously responded to treatment with pyrimidine-based drug and/or platinum-containing drug. The US Patent does not claim the CAPRIN-1 antibody comprising CDR SEQ ID NOs:37-39 and 41-43 comprise VH and VL instant SEQ ID NOs:39 and 43.
Azmy teaches as set forth above and renders obvious the addition of gemcitabine and carboplatin to the composition claimed by the US Patent for the reasons set forth above. Azmy renders obvious treating previously treated and refractory liver cancer patients for the reasons set forth above.
Okano teaches the known VH and VL sequences of SEQ ID NOs:39 and 43 that comprise the CDR SEQ ID NOs:37-39 and 41-43 of the CAPRIN-1 antibody claimed by the US Patent. Okano also teaches treating liver cancer with the CAPRIN-1 antibody.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to utilize the CAPRIN-1 antibody taught by Okano in the composition of the US Patent. One would have been motivated to, and have a reasonable expectation of success to, because Okano teaches the complete VH and VL sequence of an antibody comprising the CDR sequences of the CAPRIN-1 antibody claimed by the US Patent, and teaches using it for the same purpose as the US Patent.
13. Claims 4, 6, 8-12, 14, and 17-22 remain/are are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,274,745 in view of Suresh et al (2007, Journal of Clinical Oncology, 25; number 18, suppl, abstract 15102); and Azmy et al (International Scholarly Research Notices, 2012, article 420931).
The US Patent claims a pharmaceutical composition comprising a conjugate of a CAPRIN-1 antibody, wherein the antibody has immunological reactivity with CAPRIN-1 SEQ ID NO:2 or 31 (identical to instant SEQ ID NOs:2 and 31), wherein the antibody comprises instant CDR SEQ ID NOs:36-38 and 40-42, and instant VH and VL SEQ ID NOs:39 and 43; wherein the antibody is monoclonal, humanized; wherein the pharmaceutical composition binds CAPRIN-1 protein on the cell membrane surface of cancer cells, including ovary, liver, and gallbladder cancer; and a method of treating cancer expressing CAPIN-1 comprising administering the pharmaceutical composition.
The US Patent does not claim the composition further comprises antitumor agents combined with CAPRIN-1 antibody for liver cancer or gall bladder cancer treatment that are gemcitabine and carboplatin. The US Patent does not claim the gallbladder or liver cancer: i) is relapsed, previously treated with platinum-based therapy, ii) has not previously responded to cancer treatment with a medicament other than CAPRIN-1 antibody and a pyrimidine-based drug and carboplatin together or separately, or iii) has not previously responded to treatment with pyrimidine-based drug and/or platinum-containing drug.
Azmy teaches as set forth above and renders obvious the addition of gemcitabine and carboplatin to the composition claimed by the US Patent for the reasons set forth above. Azmy renders obvious treating previously treated and refractory liver cancer patients for the reasons set forth above.
Suresh teaches as set forth above and renders obvious the addition of gemcitabine and carboplatin to the composition claimed by the US Patent for the reasons set forth above. Suresh renders obvious treating previously treated and refractory gallbladder cancer patients for the reasons set forth above.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to add carboplatin and gemcitabine to the composition of the US Patent intended for the treatment of liver and gallbladder cancer. One would have been motivated to, and have a reasonable expectation of success to, because Suresh and Azmy teach gemcitabine and carboplatin are known and established for the treatment of liver and gallbladder cancer, and gemcitabine and carboplatin are synergistic. Those of skill in the art recognize that the liver or gallbladder cancer therapeutic agents, CAPRIN-1 antibody, gemcitabine, and carboplatin, all taught or known to treat liver or gallbladder cancer, could have been combined by known methods, and that in combination, each agent of the composition merely would have performed the same function as they did separately, and one of ordinary skill in the art would have recognized that the results of the combination would predictably treat liver or gallbladder cancer.
Response to Arguments
14. Applicants request the rejections on the ground of nonstatutory double patenting be held in abeyance until allowable subject matter is found.
15. No terminal disclaimers have been filed and no traversal is presented. The rejections on the ground of nonstatutory double patenting are maintained.
16. Conclusion: No claim is allowed.
17. All other objections and rejections recited in the Office Action mailed September 17, 2025 are hereby withdrawn in view of amendments. The rejection of claims under 35 USC 102 as being anticipated by NCT03872947 is withdrawn in view of a 102(b)(1) exception, wherein Applicants provided a 37 CFR 1.130(a) declaration stating NCT03872947 was an intervening disclosure published by a third party from information disclosed directly by the applicant Toray Industries. The rejection of claims under 35 USC 102 as being anticipated by US Patent 9,180,187, Ido, is withdrawn in view of amendments canceling composition claims and adding limitations of treatment with gemcitabine and carboplatin to claim 17, of which Ido does not anticipate.
18. Conclusion: No claim is allowed.
19. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
20. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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/Laura B Goddard/Primary Examiner, Art Unit 1642