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 .
Election/Restrictions
1. Applicant’s election without traverse of renin-angiotensin inhibitors, temperature-responsive polymer, and hyaluronic acid in the reply filed on 11/10/2025 is acknowledged.
Upon further considerations, the species election requirement for the different polymers (claims 9, 11, and 17) and additional immunomodulatory agents is withdrawn.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 5-7, 10, 12-16, 18-20, 25, 26, 28-32, 35, 36, 39-43, and 46-48 have been amended.
Claims 1-4, 8, 9, 11, 17, 21-24, 27, 33, 34, 37, 38, 44, 45, and 49 are pending and under examination.
Claim Objections
2. Claim 8 is objected to because of the recitation “TGFβR1R1”. Correction to “TGFβR1” is required.
Double Patenting
3. 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 U SPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re V ogel, 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.
4. Claims 1-4, 8, 9, 11, 17, 21-24, 27, 32, 34, 37, 38, 45, and 49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6, 7, 11, 18, 19, 22, 25, 30, 32, 33, and 42 of copending Application No. 18/274,754 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass the same method for treating cancer by administering the same composition comprising hydrogel and immunomodulatory molecules. Application claims 7 and 11 define that the immunomodulatory molecule could be an angiotensin II receptor inhibitor (i.e., a modulator of myeloid-derived suppressor/neutrophil function, as recited in the instant claims 1-3 and 8) and/or a modulator of innate immunity (such as a TLR7/8 agonist).
The application claim 1 recites a method comprising the step of administering to target site comprising a lymph dissection site; application claims 19 and 22 define that the method also comprises tumor resection and administering the composition at the tumor resection site. It is noted that the term “comprising” recited in the instant claims does not exclude the additional steps of dissecting a lymph node and administering the composition at the lymph node dissection site, as recited in the application claims.
Thus, the patent claims and the application claims are obvious variants.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112(b)
5. 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.
6. Claims 8 and 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 recites “adenosine pathway (CD39, CD73, A2AR, A2BR)”. It is noted that CD39, CD73, A2AR, and A2BR are only examples of some of the multiple species belonging to the genus “adenosine pathway” (Allard, Nature, 2020, 17: 611-629; see p. 611, column 2 through p. 612, column 2). Thus, the recitation of within parenthesis renders the claim indefinite because it is unclear whether it is part of the claimed invention.
Claim 8 also recites “CC chemokine inhibitors (e.g., CCR inhibitors, CCL inhibitors), CXC chemokine inhibitors (e.g., CXCR inhibitors, CXCL inhibitors)”. The considerations above also apply to these recitations, as it is unclear whether the examples within the parenthesis are part of the claimed invention.
Claim 17 is indefinite as being both incomplete, by its dependence on a cancelled claim; and for lack of antecedent basis for its limitation which is not present in the cancelled base claim.
Thus, the metes and bounds of the claims cannot be determined and the claims are indefinite.
For examination purposes, claim 17 is reasonably interpreted as depending upon claim 11. Amending claim 17 to make it dependent upon claim 11 would obviate its rejection under 35 U.S.C. 112(b).
Claim Rejections - 35 USC § 102
7. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
8. Claims 1, 21-24, 27, 33, 34, 37, 38, 45, and 49 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Goldberg et al. (WO 18/045058; cited on the IDS filed on 08/28/2023).
Goldberg et al. teach a method for treating cancer in a subject, the method comprising intraoperatively implanting a hyaluronic acid (HA) hydrogel comprising an innate immune response activator into a tumor rejection site in the subject; the method is performed without T-cell adoptive transfer; the activator of the innate immune response is a modulator of myeloid-derived suppressor cells (MDSCs) (claims 1, 21, 23, 24, 27, 34, and 49) (see [0002]; [0012]; [0017]; [0058]; [0168]-[0169]; [0174]; [0186]; [0266]-[0267]; [0630]; [0636]-[0637]; [0641]; [0717]-[0720]).
With respect to claim 22, Goldberg et al. teach implanting the hydrogel after the removal of more than 99% of the tumor, i.e., the rejection site is characterized by the absence of gross residual tumor antigen (see [0638]; [0716]).
With respect to claim 33, Goldberg et al. teach that the hydrogel has a storage modulus of 500-2000 Pa and it is biodegradable in vivo (see [0016]; [0558]; [0663]).
With respect to claims 37 and 38, Goldberg et al. teach that the hydrogel could further comprise an activator of adaptive immune responses (see [0166]; [0168]).
With respect to claim 45, Goldberg et al. teach that the hydrogel extends the modulator release and more modulator is found at the tumor rejection site at 24 h as compared to the modulator administered as a solution (see [0170]).
Thus, Goldberg et al. teach all claim limitations and anticipate the claimed invention.
Claim Rejections - 35 USC § 103
9. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
10. Claims 1-4, 21-24, 27, 33, 34, 37, 38, 44, 45, and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Goldberg et al., in view of Lang et al. (Clin. Cancer Res., 2018: 24: 4834-4844).
The teachings of Goldberg et al. are applied as above for claims 1, 21-24, 27, 33, 34, 37, 38, 45, and 49. Although Goldberg et al. teach an MDSCs modulator, Goldberg et al. do not specifically teach that the MDSCs are neutrophils (claims 2 and 3). Lang et al. teach that the CD66b+/CD16+/CD16+ PMN-MDSC neutrophils have the highest arginase I expression and activity, and exhibit very strong T-cell-suppressive activity characterized by suppressed T-cell proliferation and cytokine production. Lang et al. teach that arginase I pathway is the major pathway involved in inhibition by the CD66b+/CD16+/CD16+ PMN-MDSCs; using arginase inhibitors restores T-cell activity. Lang et al. suggest treating cancer by targeting the CD66b+/CD16+/CD16+ PMN-MDSCs (see Abstract; p. 4839; p. 4843, column 1 and column 2, last paragraph).
Based on these teachings, one of skill in the art would have found obvious to use an arginase inhibitor as the MDSCs modulator in Goldberg et al. to achieve the predictable result of obtaining a composition capable of treating cancer by reversing the immunosuppressive activity of the CD66b+/CD11b+/CD16+ PMN-MDSC neutrophils. By using this composition as taught by Goldberg et al., one of skill in the art would have restored the T-cells cytokine production (claim 4).
With respect to claim 44, based on the teachings in the cited prior art, one of skill in the art would have reasonably concluded that the hydrogel comprising the arginase inhibitor capable of reversing the immunosuppressive activity of neutrophils would provide enhanced survival rate in subjects with or without metastases compared to administering the hydrogel by itself.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
11. Claims 1-4, 8, 21-24, 27, 33, 34, 37, 38, 44, 45, and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Goldberg et al. taken with Lang et al., in further view of Nakamura et al. (Cancer Science, 2018, 109: 54-64).
The teachings of Goldberg et al. and Lang et al. are applied as above for claims 1-4, 21-24, 27, 33, 34, 37, 38, 44, 45, and 49. Goldberg et al. and Lang et al. do not teach a renin-angiotensin system inhibitor (claim 8). Nakamura et al. teach that the angiotensin II receptor blockers (ARBs) significantly reduces the immunosuppressive activity of the CD11b+ MDSCs by decreasing the production of arginase and immunosuppressive cytokines; Nakamura et al. suggests using ARBs in cancer therapy (see Abstract; p. 58, column 2, third full paragraph). Based on these teachings, one of skill in the art would have found obvious to replace the arginase inhibitor with an ARB, to achieve the predictable result of obtaining a composition capable of treating cancer by reversing the immunosuppressive activity, including the immunosuppressive activity of the CD66b+/CD11b+/CD16+ PMN-MDSC neutrophils.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
12. Claims 1, 21-24, 27, 33, 34, 37, 38, 45, and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Goldberg et al., in view of Chen et al. (Int. J. Mol. Sci., 2018, 19: 1-17).
The teachings of Goldberg et al. are applied as above for claims 1, 21-24, 27, 33, 34, 37, 38, 45, and 49. Goldberg et al. do not teach a thermosensitive hydrogel (claims 9, 11, and 17). Chen et al. teach thermosensitive hydrogels comprising HA suitable for the in vivo controlled release of anti-cancer therapeutic agents (see Abstract). One of skill in the art would have found obvious to use the thermosensitive HA-comprising hydrogel in the method taught by Goldberg et al., to achieve the predictable result of delivering the MDSCs modulator to the tumor rejection site.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Examiner Comments
13. It is suggested that claim 44 be amended as follows:
The method of claim 1, wherein the subject is an animal with spontaneous metastases and wherein administering the combination at the tumor resection site results in a higher percent survival rate compared to administering the biomaterial preparation without the modulator of myeloid-derived suppressive cell function, as assessed at 2 months or 3 months after the administration.
14. No claim is allowed. No claim is free of prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILEANA POPA whose telephone number is (571)272-5546. The examiner can normally be reached 8:00 am to 4:30 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ILEANA POPA/Primary Examiner, Art Unit 1633