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 1-49, 53-55, and 57-63 have been cancelled. Claims 50-52 have been amended. Claims 64 and 65 are new.
Claims 50-52, 56, 64, and 65 are pending and under examination.
2. The objections to claims 50 and 51 are withdrawn in response to the amendments filed on 01/10/2026.
The double patenting and obviousness-type rejections are withdrawn in response
the amendment limiting the nucleic acid to one of mRNA, siRNA, and miRNA. New grounds of rejection are set forth below.
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 e Terminal Disclaimers, refer to www.uspto.gov/patents/apply/applying- online/eterminal-disclaimer.
4. Claims 50, 56, and 65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,358,531, in view of all Gosh et al. (Macromolecules, 2006, 39: 5595-5597), Kabanov et al. (Bioconjugate Chem, 1993, 4: 448-454), and Tavernier et al. (J. Control. Rel., 2011, 150: 238-247). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass a method for delivering a molecule of interest to a target cell by using similar crosslinked nanogels encapsulating the molecule of interest. The instant specification discloses that the targeted cells are at a biological site (see [0069]; [0073]; [0075]). The patent specification discloses that the nanogel is obtained by mixing the polymer with the molecule of interest followed by crosslinking (see column 35, line 34 through column 36, line 3).
While the patent claims recite that the molecule of interest could be a therapeutic agent, the patent claims do not recite that the therapeutic agent is an mRNA, nor do they recite that the nitrogen is substituted by “R”. However, Gosh et al. teach that copolymers comprising pyridyl disulfide (such as the polymer recited in the patent claims) are useful for obtaining carriers for gene delivery (see p. 5596). Kabanov et al. teach quaternizing pyridine by reacting the pyridine nitrogen with alkyl halides to obtain carriers for nucleic acid delivery; Kabanov et al. teach that the alkyl halide could be ethyl bromide and exemplifies plasmid as the nucleic acid (see Abstract; p. 449, column 1). Tavernier et al. teach mRNA as an alternative to pDNA, which offers advantages over pDNA such as lack of insertional mutagenesis, lack of immunogenic effects, and ability to transfect quiescent or slow proliferating cells as mRNA does not need nuclear localization for expression (see p. 239, paragraph bridging columns 1 and 2; p. 240, column 1, first paragraph). Based on these teachings, one of skill in the art would have found obvious to modify the patent claims by quaternizing the pyridine present on the polymer with ethyl bromide and further use an mRNA as the molecule of interest to achieve the predictable result of obtaining a nanogel for gene therapy, when gene therapy was needed. By doing so, one of skill in the art would have obtained a copolymer were R is C2 alkyl and would have formed an electrostatic complex between the mRNA and the obtained polymer before the crosslinking step, as recited in the instant claim 50.
Thus, the patent claims and the application claims are obvious variants.
5. Claims 50-52, 56, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,358,531, in view of all Gosh et al. (Macromolecules, 2006, 39: 5595-5597), Kabanov et al. (Bioconjugate Chem, 1993, 4: 448-454), and Lee et al. (Biotechnology Advances, 2013, 31: 491-503). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass a method for delivering a molecule of interest to a target cell by using similar crosslinked nanogels encapsulating the molecule of interest. The instant specification discloses that the targeted cells are at a biological site (see [0069]; [0073]; [0075]). The patent specification discloses that the nanogel is obtained by mixing the polymer with the molecule of interest followed by crosslinking (see column 35, line 34 through column 36, line 3).
While the patent claims recite that the molecule of interest could be a therapeutic agent, the patent claims do not recite that the therapeutic agent is siRNA or miRNA, nor do they recite that the nitrogen is substituted by “R”, as required by the instant claims 50-52 and 64. However, Gosh et al. teach that copolymers comprising pyridyl disulfide (such as the polymer recited in the patent claims) are useful for obtaining carriers for gene delivery (see p. 5596). Kabanov et al. teach quaternizing pyridine by reacting the pyridine nitrogen with alkyl halides to obtain carriers for nucleic acid delivery; Kabanov et al. teach that the alkyl halide could be ethyl bromide (see Abstract; p. 449, column 1). Lee et al. teach that both siRNA and miRNA regulate gene expression via RNAi. Lee et al. teach clinical trials using either siRNA (i.e., dsRNA) or miRNA for treating a variety of diseases (see p. 492, column 1, first two paragraphs; p. 493, Table 1). One of skill in the art would have found obvious to use either an siRNA or an miRNA as the therapeutic agent in the patent claims, to achieve the predictable result of obtaining a nanogel suitable for inhibiting the expression of a target dysregulated gene, when inhibiting the expression of such a gene was needed. By doing so, one of skill in the art would have obtained a copolymer were R is C2 alkyl and would have formed an electrostatic complex between the siRNA or miRNA and the obtained polymer before the crosslinking step, as recited in the instant claim 50.
Thus, the patent claims and the application claims are obvious variants.
6. Claims 50, 56, and 65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 9,592,302, in view of all Gosh et al., Kabanov et al., and Tavernier et al. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass a method for delivering a molecule of interest to a target cell by using similar crosslinked nanogels encapsulating the molecule of interest. The instant specification discloses that the targeted cells are at a biological site (see [0069]; [0073]; [0075]). The patent specification discloses that the nanogel is obtained by mixing the polymer with the molecule of interest followed by crosslinking (see column 35, line 34 through column 36, line 3).
While the patent claims recite that the molecule of interest could be a therapeutic agent, the patent claims do not recite that the therapeutic agent is an mRNA, nor do they recite that the nitrogen is substituted by “R”. However, Gosh et al. teach that copolymers comprising pyridyl disulfide (such as the polymer recited in the patent claims) are useful for obtaining carriers for gene delivery (see p. 5596). Kabanov et al. teach quaternizing pyridine by reacting the pyridine nitrogen with alkyl halides to obtain carriers for nucleic acid delivery; Kabanov et al. teach that the alkyl halide could be ethyl bromide and exemplifies plasmid as the nucleic acid (see Abstract; p. 449, column 1). Tavernier et al. teach mRNA as an alternative to pDNA, which offers advantages over pDNA such as lack of insertional mutagenesis, lack of immunogenic effects, and ability to transfect quiescent or slow proliferating cells as mRNA does not need nuclear localization for expression (see p. 239, paragraph bridging columns 1 and 2; p. 240, column 1, first paragraph). Based on these teachings, one of skill in the art would have found obvious to modify the patent claims by quaternizing the pyridine present on the polymer with ethyl bromide and further use an mRNA as the molecule of interest to achieve the predictable result of obtaining a nanogel for gene therapy, when gene therapy was needed. By doing so, one of skill in the art would have obtained a copolymer were R is C2 alkyl and would have formed an electrostatic complex between the mRNA and the obtained polymer before the crosslinking step, as recited in the instant claim 50.
Thus, the patent claims and the application claims are obvious variants.
7. Claims 50-52, 56, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 9,592,302, in view of all Gosh et al. (Macromolecules, 2006, 39: 5595-5597), Kabanov et al. (Bioconjugate Chem, 1993, 4: 448-454), and Lee et al. (Biotechnology Advances, 2013, 31: 491-503). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets encompass a method for delivering a molecule of interest to a target cell by using similar crosslinked nanogels encapsulating the molecule of interest. The instant specification discloses that the targeted cells are at a biological site (see [0069]; [0073]; [0075]). The patent specification discloses that the nanogel is obtained by mixing the polymer with the molecule of interest followed by crosslinking (see column 35, line 34 through column 36, line 3).
While the patent claims recite that the molecule of interest could be a therapeutic agent, the patent claims do not recite that the therapeutic agent is siRNA or miRNA, nor do they recite that the nitrogen is substituted by “R”, as required by the instant claims 50-52 and 64. However, Gosh et al. teach that copolymers comprising pyridyl disulfide (such as the polymer recited in the patent claims) are useful for obtaining carriers for gene delivery (see p. 5596). Kabanov et al. teach quaternizing pyridine by reacting the pyridine nitrogen with alkyl halides to obtain carriers for nucleic acid delivery; Kabanov et al. teach that the alkyl halide could be ethyl bromide (see Abstract; p. 449, column 1). Lee et al. teach that both siRNA and miRNA regulate gene expression via RNAi. Lee et al. teach clinical trials using either siRNA (i.e., dsRNA) or miRNA for treating a variety of diseases (see p. 492, column 1, first two paragraphs; p. 493, Table 1). One of skill in the art would have found obvious to use either an siRNA or an miRNA as the therapeutic agent in the patent claims, to achieve the predictable result of obtaining a nanogel suitable for inhibiting the expression of a target dysregulated gene, when inhibiting the expression of such a gene was needed. By doing so, one of skill in the art would have obtained a copolymer were R is C2 alkyl and would have formed an electrostatic complex between the siRNA or miRNA and the obtained polymer before the crosslinking step, as recited in the instant claim 50.
Thus, the patent claims and the application claims are obvious variants.
Claim Rejections - 35 USC § 103
8. 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.
9. Claims 50, 56, and 65 are rejected under 35 U.S.C. 103 as being unpatentable over Thayumanavan (PGPUB 2014/0112881), in view of all Gosh et al. (Macromolecules, 39: 5595-5597), Kabanov et al. (Bioconjugate Chem, 1993, 4: 448-454), and Tavernier et al. (J. Control. Rel., 2011, 150: 238-247).
Thayumanavan teaches a cross-linked nanogel encapsulating a molecule of interest; the cross-linked nanogel could be functionalized with targeting ligands. Thayumanavan teaches using the cross-linked nanogel in a method for the controlled release of the molecule of interest within the targeted cells. The polymer has the structure:
PNG
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188
192
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The cross-linked nanogel is obtained by forming a non-covalent complex between the therapeutic molecule and the block co-polymer, followed by crosslinking with DTT to reduce the pyridyl disulfide (PDS) group and form the cross-linked nanogel encapsulating the therapeutic molecule (claims 50 and 56) (see Abstract; [0016]; [0019]; [0147]; [0151]; [0229]; claim 28; Fig. 1).
Thayumanavan do not teach that the pyridine nitrogen is substituted by “R” nor do they teach a nucleic acid (claims 50-52). Gosh et al. teach that copolymers comprising PDS such as Thayumanavan’ polymer are useful for obtaining carriers for gene delivery (see p. 5596). Furthermore, quaternizing the pyridine by reacting the pyridine nitrogen with alkyl halides to obtain carriers for nucleic acid delivery was practiced in the prior art, for example, by Kabanov et al.; Kabanov et al. teach that the alkyl halide could be ethyl bromide and exemplifies a DNA plasmid (pDNA) as the nucleic acid is (see Abstract; p. 449, column 1). Based on these teachings, one of skill in the art would have found obvious to modify Thayumanavan by quaternizing the pyridine present on the polymer with ethyl bromide and further use a pDNA encoding a therapeutic gene as the molecule of interest to achieve the predictable result of obtaining a nanogel for suitable for gene therapy, when gene therapy was needed.
Thayumanavan, Gosh et al., and Kabanov et al. do not teach an mRNA (claims 50 and 65). Tavernier et al. teach mRNA as an alternative to pDNA, which offers advantages over pDNA such as lack of insertional mutagenesis, lack of immunogenic effects, and ability to transfect quiescent or slow proliferating cells as mRNA does not need nuclear localization for expression (see p. 239, paragraph bridging columns 1 and 2; p. 240, column 1, first paragraph). Based on these teachings, replacing the pDNA with an mRNA would have been obvious to one of skill in the art to achieve the predictable result of obtaining a nanogel suitable for gene therapy. By doing so, one of skill in the art would have obtained a copolymer were R is C2 alkyl and would have formed an electrostatic complex between the mRNA and the obtained polymer before the crosslinking step (claim 50).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
10. Claims 50-52, 56, and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Thayumanavan, in view of all Gosh et al., Kabanov et al., and Lee et al. (Biotechnology Advances, 2013, 31: 491-503).
Thayumanavan teaches a cross-linked nanogel encapsulating a molecule of interest, where the cross-linked nanogel could be functionalized with targeting ligands. Thayumanavan teaches using the cross-linked nanogel in a method for the controlled release of the molecule of interest within the targeted cells. The polymer has the structure:
PNG
media_image1.png
188
192
media_image1.png
Greyscale
The cross-linked nanogel is obtained by forming a non-covalent complex between the therapeutic molecule and the block co-polymer, followed by crosslinking with DTT to reduce the pyridyl disulfide (PDS) group and form the cross-linked nanogel encapsulating the therapeutic molecule (claims 50 and 56) (see Abstract; [0016]; [0019]; [0147]; [0151]; [0229]; claim 28; Fig. 1).
Thayumanavan do not teach that the pyridine nitrogen is substituted by “R” nor do they teach a nucleic acid as recited in claims 50-52. Gosh et al. teach that copolymers comprising PDS such as Thayumanavan’ polymer are useful for obtaining carriers for gene delivery (see p. 5596). Furthermore, quaternizing the pyridine by reacting the pyridine nitrogen with alkyl halides to obtain carriers for nucleic acid delivery was practiced in the prior art, for example, by Kabanov et al.; Kabanov et al. teach that the alkyl halide could be ethyl bromide (see Abstract; p. 449, column 1). Based on these teachings, one of skill in the art would have found obvious to modify Thayumanavan by quaternizing the pyridine present on the polymer with ethyl bromide and further use a therapeutic nucleic acid as the molecule of interest to achieve the predictable result of obtaining a nanogel for suitable for gene therapy, when gene therapy was needed.
Thayumanavan, Gosh et al., and Kabanov et al. do not teach that the therapeutic nucleic acid is an miRNA or siRNA (claims 50-52 and 64). Lee et al. teach that both siRNA and miRNA regulate gene expression via RNAi. Lee et al. teach clinical trials using either siRNA (i.e., dsRNA) or miRNA for treating a variety of diseases (see p. 492, column 1, first two paragraphs; p. 493, Table 1). One of skill in the art would have found obvious to use either an siRNA or an miRNA as the therapeutic nucleic acid, to achieve the predictable result of obtaining a nanogel suitable for inhibiting the expression of a target dysregulated gene, when inhibiting the expression of such a gene was needed. By doing so, one of skill in the art would have obtained a copolymer were R is C2 alkyl and would have formed an electrostatic complex between the siRNA or miRNA and the obtained polymer before the crosslinking step (claim 50).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Response to Arguments
11. The arguments are answered below to the extent that they pertain to the new rejections.
The argument that none of Thayumanavan, Gosh, and Kabanov disclose an mRNA, dsRNA, siRNA, or miRNA is not found persuasive because Thayumanavan, Gosh, and Kabanov do not have to disclose such an RNA. As set forth in the rejections, these nucleic acids are disclosed by Tavernier and Lee, who also provide the motivation to modify Thayumanavan, Gosh, and Kabanov by using mRNA, siRNA (i.e., dsRNA), or miRNA for gene therapy.
The arguments of unpredictability, lack of reasonable expectation of success, and undue experimentation are not found persuasive because they are not supported by any evidence.
With respect to the argument regarding an objective reason to combine the teachings of the cited references, the rejection clearly provide the reason to combine. Furthermore, using the cross-linked nanogel to deliver nucleic acids would not change the intended purpose, which is the delivery of therapeutic agents.
With respect to the double patenting, the applicant argues that the patent claims do not recite mRNA, dsRNA, siRNA, or miRNA.
However, there is no requirement for the patent claims to recite mRNA, dsRNA, siRNA, or miRNA. The double patenting rejections are based on the obviousness, not anticipation, rationale. Thus, the analysis employed is similar to the one under 35 USC § 103 and can use secondary references supporting the obviousness analysis (see MPEP 804 II B 3).
Conclusion
12. 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