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
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 8/18/2026 has been entered.
Claims 24, 34, 37, 39, 43, 48, 49, 51-53, and 56-63 are now pending. Claims 24 and 57 are amended. Claims 58-63 are new.
The 112(b) rejections cited in Office Action 2/20/2026 are hereby withdrawn in view of amendments.
Claims 24, 34, 37, 39, 43, 48, 49, 51-53, and 56-63 are currently being examined.
New Rejections
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.
Claims 52 and 62 depend on a canceled claim. There is insufficient antecedent basis for this limitation in the claim.
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, 39, 43, 48, 49, 51-52, 56, and 61-63 are 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; of record), Cheung et WO2020086758 A1; Priority date 10/23/2018; of record), Barnett (US8759293 B2; Published 11/15/2012), and Hall et al (US20160106858 A1; Published 4/21/2016).
Nimni teaches a method for treating breast cancer. [0006-0008, 00112] 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]. Regarding claim 63, 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 or colon cancer. [0056, 00112]
Regarding claims 39 and 56, Nimni teaches that pharmaceutical composition can be administered intravenously (systemically). [0211] Regarding claims 48 and 49, Nimni teaches that the polypeptide is covalently linked to the cytotoxic agent through a cleavable linker, such as a pH-cleavable linker or a hydrazone linker. Nimin teaches that the present invention is activated in slightly acidic conditions around pH 6.0 of the tumor interstitium, that is less than of a pH 7.4 [0086, 0146, 0169] Nimni does not teach that the polypeptide is not operatively linked to a particle or nanovesicle as recited in claim 51.
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] Regarding claim 43, Nimni teaches that the subject treated include patients who have received prior therapy or will receive therapy for the malignancy. [0209-0210] Nimni further teaches and demonstrates in Figure 7 that paclitaxel associated with albumin (Abraxane) to collagen exhibited greater retention on a collagen matrix and that CBD-bound to Abraxane enhanced chemotherapeutic effects in mice bearing colon cancer cells in a mouse mode. [0056, 0262, 0263]
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 instantly claimed 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
Hall teaches the use of bifunctional fusion polymers that contain two or more domains. One domain contains a collagenous protein and the second binds to a pharmaceutical agent. [Abstract] Hall teaches that the polymers also bind to human serum albumin, which in turn can bind to a therapeutic agent via linker. [0019] Hall teaches that the compositions can be used to treat cancer, such as breast or colon cancer and that the anti-cancer agent and bifunctional fusion polymer should be mixed at a specific ratio. Hall teaches that the drug teaches may be doxorubicin. [0040, 0161, 0171-0172, 0214]
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, (4) Barnett teaches the known collagen binding sequence, SEQ ID NO: 1, and teaches that it can be used in formulations for treatment methods, and (5) Hall teaches known methods of using bifunctional fusion polymers that have a collagen binding domain linked to an albumin, which is further linked to a chemotherapeutic agent, and teaches that the albumin and anti-cancer agents are mixed at specific ratios. 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, 53, 56, 57, 58, 59, and 60 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) Barnett (US8759293 B2; Published 11/15/2012), and Hall et al (US20160106858 A1; Published 4/21/2016), as applied to claims 24, 39, 43, 48, 49, 51-52, 56, and 61-63 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; of record) and Bilgin et al (Targeting the PD-1 pathway: a new hope for gastrointestinal cancers. Curr Med Res Opin. 2017 Apr;33(4):749-759).
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]
Bilgin teaches the use of immunotherapy, such as anti-PD1 and anti-PD-L1 antibodies, for the treatment of colon cancer. Bilgin teaches that GI cancers are the most common cancers in the world and that immune checkpoints are the key steps for immune escape and tumor development. Bilgin teaches that immune checkpoint inhibition has promising efficacy in colon cancers and teaches Both pembrolizumab and nivolumab show promising efficacy with acceptable safety data in published trials in GI cancers, especially in refractory MSI positive metastatic colorectal cancer. [Abstract]
It is noted that claims 34, 37 and 57 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, and (4) Bilgin teaches the use of immune checkpoint inhibitors for the treatment of colon cancer. Given the known need to treat breast and colon cancer and given the known methods of using immune checkpoint inhibitors to treat both of these cancers, 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 argues that there is little or no significant enhancement of treatment with the CBD-conjugated Abraxane as compared to Abraxane without conjugation to CBD in Nimni. 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.
Applicants’ 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] Nimni also demonstrates in Figure 7 that paclitaxel associated with albumin (Abraxane) to collagen exhibited greater retention on a collagen matrix and that CBD-bound to Abraxane enhanced chemotherapeutic effects in mice bearing colon cancer cells in a mouse mode. Thus, the art demonstrates that there is enhanced treatment of cancer with a CBD-conjugated chemotherapeutic.
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 colon 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, with a reasonable expectation of success.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
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/SARAH A ALSOMAIRY/ Examiner, Art Unit 1646
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