Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
The Amendment filed 10/16/2025 in response to Office Action of 6/16/2025, is acknowledged and has been entered. Claims 24, 32, 34, 37, 39, 43, 48, and 51-57 are now pending. Claims 24, 43, 48, and 52 are amended. Claims 53-57 are new.
The 112(b) rejections cited in Office Action 6/16/2025 are hereby withdrawn in view of amendments.
Claims 24, 32, 34, 37, 39, 43, 48, and 51-57 are currently being examined.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
The terms “reducing” and “increasing” in claim 24is a relative term which renders the claim indefinite. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
New Rejections
(Necessitated by Amendments)
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.
Claim(s) 24, 32, 39, 43, and 48-55 remain rejected under 35 U.S.C. 103 as being unpatentable by Nimni et al (WO2012112690 A1; Published 8/23/2012; copy in IDS 4/7/2022), in view of Choe et al (Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides; Materials 2016, 9(12), 994), Cheung et WO2020086758 A1; Priority date 10/23/2018), and Barnett (US8759293 B2; Published 11/15/2012).
Nimni teaches a method for treating cancer, reducing non-specific toxicity of treatment comprising a cytotoxic agent, comprising administering a composition. [0006-0008] In paragraph [0010], Nimni teaches that the composition comprising a therapeutic agent, an intermediate release linker bound to the therapeutic agent, and a targeting moiety bound to the intermediate linker, wherein the targeting moiety binds to native collagen fibers. Nimni teaches that the targeting moiety can be a collagen binding site, and in paragraph [0022]. Nimni teaches that the therapeutic agent may be a cytotoxic agent, such as an anti-neoplastic therapeutic agent doxorubicin. Nimni teaches that the composition comprises (1) a therapeutic agent, (2) an intermediate release linker bound to the therapeutic agent, and (3) targeting moiety bound to the intermediate linker. [0022] Nimni teaches that the cytotoxic agent may be selected from agents, including doxorubicin, and used for the treatment of solid cancers, such as breast cancer. [0012]
Regarding claims 39 and 56, Nimni teaches that pharmaceutical composition can be administered intravenously (systemically). [0211] Nimni teaches there is a need for improved route of delivery of anti-cancer medications that targets the cancer cells, and more specifically improves the bioavailability of anticancer medications, and reducing the toxicity associated with the administration of anti-cancer medications and not contributing any additional toxicities. [0006-0009] Nimni teaches that the subject treated include patients who have received prior therapy, or will receive therapy for the malignancy. [0209-0210]
Regarding claims 48, Nimni teaches that the polypeptide is covalently linked to the cytotoxic agent through a cleavable linker, such as a pH-cleavable linker, hydrazone linker, [0146] Regarding claim 50, Nimni teaches that the polypeptide comprises a collagen binding domain from von Willebrand factor (VWF). [0087, 0089]
Nimni teaches that another composition wherein the targeting composition is bound to a polypeptide or protein therapeutic agent [claim 101], however, does not explicitly teach that Fc domain operatively linked to a collagen binding domain and does not teach that the collagen binding domain comprises the amino acid sequence of SEQ ID NO: 1 or 14.
Choe teaches the use of IgG Fc binding ligands. Choe teaches that the Fc binding domain is the primary binding site for effector proteins. Choe teaches that Fc-binding domains are highly desirable because Fc-binding ligands do not interfere with the antigen binding ability of immunoglobulins. [pg 13, Conclusion]
Cheung teaches the use of Fc domains and Fc fusion proteins that comprise collagen-binding domains. [0061, 0274]
Barnett teaches preparations of collagen binding domains and teaches amino acid SEQ ID NO: 39, which matches 100% to instantly claimed SEQ ID NO: 1. See sequence alignment below. Barnett teaches that the polypeptides can be formulated for treatment and can be combined with vehicles, such as albumin. Thus, Barnett teaches the known sequence of the collagen binding domain.
RESULT 7
US-13-509-309-39
Sequence 39, US/13509309
Patent No. 8759293
GENERAL INFORMATION
APPLICANT: Grifols Therapeutics Inc.
APPLICANT: Barnett, Thomas
TITLE OF INVENTION: VON WILLEBRAND FACTOR (VWF)-CONTAINING PREPARATIONS, AND METHODS,
TITLE OF INVENTION: KITS, AND USES RELATED THERETO
FILE REFERENCE: T126 2110US.PCT
CURRENT APPLICATION NUMBER: US/13/509,309
CURRENT FILING DATE: 2012-05-21
PRIOR APPLICATION NUMBER: 61/261,145
PRIOR FILING DATE: 2009-11-13
PRIOR APPLICATION NUMBER: PCT/US2010/056496
PRIOR FILING DATE: 2010-11-12
NUMBER OF SEQ ID NOS: 43
SEQ ID NO 39
LENGTH: 1365
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: von Willebrand Factor sequence
Query Match 100.0%; Score 1036; Length 1365;
Best Local Similarity 100.0%;
Matches 205; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CSGEGLQIPTLSPAPDCSQPLDVILLLDGSSSFPASYFDEMKSFAKAFISKANIGPRLTQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 929 CSGEGLQIPTLSPAPDCSQPLDVILLLDGSSSFPASYFDEMKSFAKAFISKANIGPRLTQ 988
Qy 61 VSVLQYGSITTIDVPWNVVPEKAHLLSLVDVMQREGGPSQIGDALGFAVRYLTSEMHGAR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 989 VSVLQYGSITTIDVPWNVVPEKAHLLSLVDVMQREGGPSQIGDALGFAVRYLTSEMHGAR 1048
Qy 121 PGASKAVVILVTDVSVDSVDAAADAARSNRVTVFPIGIGDRYDAAQLRILAGPAGDSNVV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1049 PGASKAVVILVTDVSVDSVDAAADAARSNRVTVFPIGIGDRYDAAQLRILAGPAGDSNVV 1108
Qy 181 KLQRIEDLPTMVTLGNSFLHKLCSG 205
|||||||||||||||||||||||||
Db 1109 KLQRIEDLPTMVTLGNSFLHKLCSG 1133
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to link the collagen binding domain comprising instantly claimed SEQ ID NO: 1 an IgG Fc domain. One would have been motivated to, and have a reasonable expectation of success: (1) Nimni teaches a method for treating cancer comprising administering a composition comprising a targeting moiety that is a collagen binding domain, (2) Choe teaches known uses of IgG Fc binding to ligands and teaches that these are highly desirable, (3) Cheung teaches uses of Fc domains that comprise collagen-binding domains, and (4) Barnett teaches the known collagen binding sequence, SEQ ID NO: 1, and teaches that it can be used in formulations for treatment methods. Given the known uses of using IgG Fc binding domains and given the known sequences of the collagen binding domain, and given the known methods of using collagen binding domains as taught by Nimni, one of skill in the art could have pursued linking the collagen binding domain comprising SEQ ID NO: 1 to a Fc domain, with a reasonable expectation of success.
Claim(s) 34, 37, 56 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Nimni et al (WO2012112690 A1; Published 8/23/2012; copy in IDS 4/7/2022), Choe et al (Fc-Binding Ligands of Immunoglobulin G: An Overview of High Affinity Proteins and Peptides; Materials 2016, 9(12), 994) and Barnett (US8759293 B2; Published 11/15/2012), as applied to claims 24, 32, 39, 43, and 48-55 above, and further in view of Swoboda et al (Immune Checkpoint Blockade for Breast Cancer. In: Gradishar, W. (eds) Optimizing Breast Cancer Management. Cancer Treatment and Research, vol 173. Springer, Cham, 2018, pp 155-165).
The teachings of Nimni and Choe are recited above. However, they do not teach that the subject has or will receive immunotherapy, wherein the immunotherapy comprises checkpoint inhibitor therapy, such as an anti-PD-1 antibody.
Swoboda teaches that immune checkpoint blockade is a common treatment for patients with breast cancer. Swoboda teaches that PD-1 and PDL1/L2 are upregulated in breast cancer. Swoboda teaches and demonstrates the effect of pembrolizumab, an anti-PD-1 antibody, immune checkpoint inhibitor, in multiple clinical trials. [pgs 158, 10.3]
Is it noted that claims 34 and 37 require that the subject has or will receive immunotherapy, wherein the immunotherapy comprises a checkpoint inhibitor therapy. This limitation would have been obvious to those of ordinary skill in the art because: (1) Nimni teaches the use of a polypeptide linked to a collagen binding domain, (2) Nimni teaches that this agent can be combined with other agents for the treatment of breast cancer, (3) Swoboda teaches that immunotherapy, such as checkpoint inhibitors, are well known agents used for the treatment of breast cancer. Given the known need to treat breast cancer, and given the known methods of using immune checkpoint inhibitors to treat breast cancer, one of skill in the art could have pursued adding immune checkpoint inhibitors to the method of Nimni, with a reasonable expectation of success.
Response to Arguments
Applicant amended claim 24 to recite that the collagen binding domain is SEQ ID NO: 1 or 14 and that the current claims have been found to have surprising and unexpected effects not found in the art. Applicant argues that there is little or no significant enhancement of treatment with the CBD-conjugated Abraxane as compared to Abraxane without conjugation to CBD. Applicant argues that the current claims are shown to have significant decrease of tumor volume and increase in survival and in breast and colon cancer mouse models and that the application demonstrates synergy for the treatment with anti-PD-1 therapy as claimed in claims 37 and 53.
Applicant’s arguments have been considered but are not persuasive. With regards to unexpected results, the MPEP states:
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 re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at “elevated temperatures” using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110C and 130C. The court affirmed the rejection of claims 1-7 and 9-10 because the term “elevated temperatures” encompassed temperatures as low as 60C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.).
Contrary to Applicant’s argument, Nimni does not need to provide a working example for obviousness or to provide a reasonable expectation of success. The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In reBorkowski, 422 F.2d 904, 164 USPQ 642, 645 (CCPA 1970). However, Nimni does demonstrate that based off their significant data, there is significant data to support the concept that effective targeting of exposed collagen fibers can be achieved for the purpose of selective drug delivery to tumor sites. [0277-0279] With regards to the combination with an anti-PD-1 antibody, it is known in the art that immunotherapy, such as anti-PD-1 antibody, are known to treat breast cancer, and Nimni teaches that the agent can be combined with other agents for the treatment of cancer. Thus, given known methods of treatment and given the known role of an anti-PD-1 antibody, one of skill in the art would have combined the two agents.
Conclusion
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.
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/SARAH A ALSOMAIRY/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678