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. Claims 5-8, 10, 12-16, 18-20, 25, 26, 28-32, 35, 36, 39-44, and 46-48
Claims 1, 9, 11, 17, 24, 27, 33, and 49 have been amended. Claims 50 and 51 are new.
Claims 1-4, 9, 17, 21-24, 27, 33, 34, 37, 38, 45, and 49-51 are pending and under examination.
2. All rejections/objections pertaining to claims 8, 11, and 44 are moot because the claims were cancelled with the reply filed on 04/30/2026.
The rejection of claim 17 under 35 U.S.C. 112(b) is withdrawn in response to the amendment cancelling to make the claim dependent upon claim 51.
The following rejections are withdrawn in response to the amendment introducing the limitation “renin-angiotensin inhibitor” in the independent claims 1 and 49:
The rejection of claims 1, 21-24, 27, 33, 34, 37, 38, 45, and 49 under 35 U.S.C. 102(a)(1) as being anticipated by Goldberg et al.;
The rejection of claims 1, 21-24, 27, 33, 34, 37, 38, 45, and 49 under 35 U.S.C. 102(a)(1) as being anticipated by Goldberg et al. (WO 18/045058);
The rejection of claims 1-4, 21-24, 27, 33, 34, 37, 38, 45, and 49 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 rejection of claims 1, 21-24, 27, 33, 34, 37, 38, 45, and 49 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).
Maintained Rejections
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 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.
4. Claims 1-4, 9, 17, 21-24, 27, 33, 34, 37, 38, 45, and 49-51 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 § 103
5. 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.
6. Claims 1-4, 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. (WO 18/045058), in view of both Lang et al. (Clin. Cancer Res., 2018: 24: 4834-4844) and Nakamura et al. (Cancer Science, 2018, 109: 54-64).
Goldberg et al. teach a method for treating cancer in a subject, the method comprising intraoperatively implanting a hyaluronic acid (HA) hydrogel comprising one or more innate immune response activators into a tumor rejection site in the subject; the method is performed without T-cell adoptive transfer; the hydrogel could comprises 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 thus, more modulator levels are found at the tumor rejection site at 24 h as compared to the modulator administered as a solution (see [0170]).
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 thus, 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+/CD11b+/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).
Goldberg et al. and Lang et al. do not teach that Goldberg et al. and Lang et al. do not teach a renin-angiotensin system inhibitor (claims 1 and 49). 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.
7. Claims 1-4, 9. 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. taken with both Lang et al. and Nakamura et al., in further view of Chen et al. (Int. J. Mol. Sci., 2018, 19: 1-17).
The teachings of Goldberg et al., Lang et al., and Nakamura et al. are applied as above for claims 1-4, 21-24, 27, 33, 34, 37, 38, 45, and 49. Goldberg et al., Lang et al., and Nakamura et al. do not teach a thermosensitive hydrogel (claims 9). 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 renin-angiotensin inhibitor to the tumor rejection site.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
New Grounds of Rejection Necessitated by Applicant’s Amendments
Claim Rejections - 35 USC § 112(d)
8. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
9. Claims 2-4 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
By broadly reciting a modulator of neutrophil function, claims 2-4 fail to limit the subject matter of the parent claim 1, which is limited to renin-angiotensin inhibitors.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
10. 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.
11. Claims 1-4, 9, 11, 17, 21-24, 27, 33, 34, 37, 38, 45, and 49-51 are rejected under 35 U.S.C. 103 as being unpatentable over Goldberg et al. taken with both Lang et al. and Nakamura et al., in further view of Jung et al. (Carbohydrate polymers, 2017, 156: 403-408).
The teachings of Goldberg et al., Lang et al., and Nakamura et al. are applied as above for claims 1-4, 21-24, 27, 33, 34, 37, 38, 45, and 49. Goldberg et al., Lang et al., and Nakamura et al. do not teach a thermosensitive hydrogel further comprising a poloxamer (claims 9, 11, 17, 50, and 51). Jung et al. teach thermosensitive hydrogels comprising HA and Pluronic F-127 (i.e., poloxamer), suitable for the in vivo controlled and sustained release of agents for various disease treatments (see Abstract; p. 408, column 1, last paragraph). One of skill in the art would have found obvious to use the thermosensitive HA- Pluronic F-127 hydrogel in the method taught by Goldberg et al., Lang et al., and Nakamura et al., to achieve the predictable result of delivering the renin-angiotensin inhibitor to the tumor rejection site.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Response to Arguments
12. The applicant argues that Goldberg discloses the MDSC modulator as an additional therapeutic agent utilized in combination with activators of innate immunity, not as the activator of innate immunity.
However, it is noted that the claims do not exclude combinations of innate immunity activators and MDSC modulators as taught by Goldberg. The combination of innate immunity activators and MDSC modulators is encompassed by the claims.
The applicant argues that one of skill in the art would not have been motivated to substitute the activator of innate immunity in Goldberg with Lang’s arginase inhibitor because neither Goldberg nor Lang teaches or suggests such a substitution.
This argument is not material to the rejection because the rejection is not based on the substitution mentioned by the applicant. The rejection is based on using an arginase inhibitor as the MDSC modulator in Goldberg, as suggested by the combined teachings of Goldberg and Lang. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
For these reasons, the argument that the rejection over Goldberg, Lang, and Nakamura cannot stand because it relies on substituting the arginase inhibitor for the innate immunity activator is not found persuasive.
The argument of lack of reasonable expectation of success is not found persuasive because it is just an argument not supported by any evidence.
The applicant points to Example 21 and Fig. 7 in the specification the therapeutic efficacy of the renin-angiotensin inhibitor in the absence of an activator of immune immunity.
However, this argument is not commensurate in scope with the claims because, as noted above, the claims encompass combinations of innate immunity activators and MDSC modulators.
The arguments addressing Nakamura individually are not found persuasive because the reference does not have to teach every claim limitation.
Conclusion
13. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/ILEANA POPA/Primary Examiner, Art Unit 1633
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