CTNF 18/475,687 CTNF 101604 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claim Status Claims 1-20 are pending in the application. Claims 17-20 are withdrawn. Claims 1-16 are currently examined. Election/Restrictions Applicant's election with traverse of Invention I (Claims 1-12) in the reply filed on Feb. 23, 2026 is acknowledged. The traversal is on the grounds that the amended claims are directed to compositions of claim 1 and the Applicant asserts that there is no excessive burden to the examiner to search. This is not found persuasive because Invention III (Claims 17-20) is a process of use and the process of using Invention I can be practiced by a materially different product (see MPEP 806.05(h)). In this case hyaluronic acid or corticosteroid injections are practiced for osteoarthritis pain. The requirement is still deemed proper and is therefore made FINAL. Therefore, claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Furthermore, the Examiner agrees to add claims 13-16; however, the Examiner notes that the restriction response is noncompliant because one specific polymer and one specific ion channel modulator was not elected. The Examiner; however, will withdraw the election of species restriction to advance prosecution. Claim Objections 07-29-01 AIA Claim 2 is objected to because of the following informalities: Spelling. It is unclear if Applicant intended “Nacetylethanomimes” in line 4 of claim 2 to recite “N-acylethanolamines”, which are known TRPV1 modulators. Applicant’s specification recites the same spelling as “Nacetylethanomimes”, which are not a recognized class of TRPV1 modulators . Appropriate correction is required. 07-29-01 AIA Claim 12 is objected to because of the following informalities: inconsistent terminology. The recitation of 0 months in line 3 of claim 12 contradicts the term “sustained”. Examiner recommends amending the claim to a more suitable measurement of time such as days . Appropriate correction is required. 07-30-03-h AIA Claim Interpretation Claim 1 is drawn to a composition and the intended use of the composition. The recitation of an intended use of the claimed invention must result in a structural difference between the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Therefore, the intended use recited in claim 1, namely that a composition for treatment of pain is not afforded patentable weight. Claim Rejections - 35 USC § 112 07-30-01 AIA The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claim 12 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Specifically, the sustained release of 0 to 12 months is not supported as the in-vitro release kinetics show over 50% of the ion channel modulator is released by about 400 hours (approximately day 16) (Figure 3), indicating a release profile on the order of weeks. Furthermore, the claimed release period of 0 to 12 months represents a broad range that is not supported by the disclosure. As set forth in MPEP 2163.05 (III) the written description is not satisfied where a specification discloses only a limited number of values or a narrow portion of a range but fails to reasonably convey possession of the full claimed range. Accordingly, the specification fails to reasonably convey possession of the full scope of the claimed range of 0 to 12 months for sustained release. 07-30-02 AIA 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. 07-34-01 Claims 2 and 9 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. With respect to claim 2, the use of the term “e.g.” renders the scope of the claim unclear. The term “e.g.” indicates an example and is inherently non-limiting, creating ambiguity. Therefore, the metes and bounds of the claim cannot be determined. With respect to claim 9, the recitation of the compounds in parentheses renders the scope of the claim unclear. It is unclear if the parenthetical compounds are intended to be limiting elements of the claimed linker, examples of suitable inkers, or optional features. The claim does not differentiate the parenthetical compounds and thus the metes and bounds of claim 9 also cannot be determined. Claim Rejections - 35 USC § 102 07-06 AIA 15-10-15 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. 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-15 AIA Claim s 1-3, 8, and 10-16 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Kohane et al. (US-20210275678-A1, Published 2021-09-09) Kohane et al. teaches conjugates of anesthetic agents including ion channel modulators, specifically sodium channel blockers such as tetrodotoxin (TTX), covalently conjugated to a biocompatible polymer backbone via a hydrolysable ester linkage with sustained release from 72 hours to 1 month (paragraph [0009], [0014] and [0144]) as required by claims 1, 3, 8, 10, and 12. They further disclose that the conjugates can include a vanilloid receptor 1( TRPV1 ) agonist with exemplary TRPV 1 agonists listed as capsaicin and resiniferatoxin (paragraph [0011]) as required by claims 2, and 14. Furthermore, Kohane et al. disclose their preferred biocompatible polymer backbones includes poly(ethylene glycol) (PEG) (paragraph [0012]) as required by claim 13. They go on to teach that any natural or synthetic polymer having –COOH or OH groups can be used to conjugate anesthetic agents, therefore, natural and synthetic polymers such hyaluronic acid could also be used (paragraph [0085]). Kohane et al. also teach the molecular weights of the polymers. Specifically, they disclose “PEGs can have molecular weights between approximately 100 Da (i.e., PEG 100 Da) and approximately 12,000 kDa (i.e., PEG 12 KDa)” (paragraph [0100]). Kohane et al. further teach the amount and size of PEG (or other hydrophilic polymer) included within the conjugates can be varied according to the desired physiological properties of the conjugate in vivo (paragraph [0105]) which overlaps with claim 15. Kohane further teaches that ion channel modulators such as capsaicin are covalently conjugated to polymer backbones via ester linkages (paragraph [0300]) having drug loadings of 44.4 ug/mg and 182.9 ug/mg (Table 10) corresponding to polymer-to-drug ratios of approximately 1:0.044 and 1:0.183, respectively, which encompasses the ranges of claims 11 and 13. They also teach the linkers and spacers between the polymer and anesthetic agent can be any small chemical entity, peptide, and carbonate terminations (paragraph [0111]). Lastly, Kohane et al. teach a syringe injectable composition (paragraphs [0126] and [0127]) as required by claim 16. Therefore, the teachings of Kohane et al. anticipate Applicant’s claims 1-3, 8, and 10-16 . Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-23-aia AIA The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. 07-20-02-aia AIA This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. 07-21-aia AIA Claim s 4-9 are rejected under 35 U.S.C. 103 as being unpatentable over Kohane et al. (US-20210275678-A1, Published 2021-09-09) as applied to claims 1-3, 8, and 10-16 above and in view of Vetter et al. (US-20140249093-A1, Published 2014-09-04) . The teachings of Kohane et al. as set forth above with respect to claims 1-3, 8, and 10-16 are relied upon and incorporated herein. Kohane et al. does not teach (A) a composition that comprises voltage gated calcium channel modulators, (B) a composition wherein the polymer is cross linked and (C) a linker selected from beta-alanine, glycine, 5-aminovaleric acid, (8-amino-3,6-dioxaoctanoic acid), or (12-amino-4,7,10-trioxadodecanoic acid). In regard to (A) Vetter et al. teaches drugs covalently linked to polymers via a linker (paragraph [0014]-[0020]). They specifically disclose preferable drugs as gabapentin and pregabalin (paragraph [0349]) as required by claim 4. In regard to (B) Vetter et al. teaches the polymer (paragraph [0064]) along with preferred embodiments such as PEG and hyaluronic acid (paragraph [0153]) and that the polymer is preferably crosslinked (paragraph [0154]) as required by claims 5 and 6. Furthermore Vetter et al. teaches the polymer has a molecular weight of 0.2 kDa to 160 kDa (paragraph [0156]) which overlaps with the range of claim 7. Because both Kohane et al. and Vetter et al. teach the molecular weights of the polymer that overlap with the claimed range, it would have been obvious to one of ordinary skill in the art to select a polymer having a molecular weight within the claimed range. In regard to (C) Vetter et al. teach the formula of their polymer linked drug as shown in Ia, Ib, Ic, and Id. Wherein D is a drug, L is the linker and POL is the polymer. The dashed line marked with an asterisk in Ic indicates attachment to a carboxyl group of a biologically active moiety D by forming a carboxylic ester comprising O and the other dashed line indicates attachment to the rest of the molecule (paragraph [0021]). Furthermore, R1 is selected from the group of alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl and cycloheteroalkyl; R2 is selected from H, alkyl, and substituted alkyl; R3 and R4 are independently selected from the group consisting of H, alkyl, and substituted alkyl; n is 0 or 1; and Q is a spacer moiety. PNG media_image1.png 128 261 media_image1.png Greyscale PNG media_image2.png 189 467 media_image2.png Greyscale PNG media_image3.png 192 439 media_image3.png Greyscale Vetter et al. discloses that the R1 group is preferred to have an alkyl or aryl group instead of a hydrogen as the steric effects enables greater control of the rate of hydrolytic degradation of such carrier linked prodrugs (paragraph [0041]). They also note the presence of the moiety R1 confers greater stability to hydrolysis of the carboxylic ester linkage due to the steric and electronic effect of the alkyl or aryl group and the steric effect may be increased by increasing the size of the alkyl or aryl group (paragraph [0041] and [0042]). Kohane et al. also teaches the linkers and can be any small chemical entity or peptide thereby encompassing amino acids such as glycine and beta-alanine (paragraph [0111]). Therefore, these teachings render obvious the substitution of known linkers required by claims 8 and 9 as both Vetter et al. and Kohane et al. teach varied linkers in the polymer conjugate. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the conjugates of Kohane et al. to include a calcium channel modulator as taught by Vetter et al. because both references are directed to polymer-based drug delivery systems designed to provide sustained release of therapeutically active agents for pain management. Substituting one known class of ion channel modulators for another represents the use of a known element for its known purpose to yield predictable results. It would have been further obvious to employ crosslinked polymer systems and to select appropriate linker species as taught by Vetter et al. because both references teach the polymer structure and linker composition may be modified to control drug release, rendering such modifications routine variations within the art. Conclusion No claims are allowed in this action. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /RAJESH JAIPRASHAD/Examiner, Art Unit 1691 /RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691 Application/Control Number: 18/475,687 Page 2 Art Unit: 1691 Application/Control Number: 18/475,687 Page 3 Art Unit: 1691 Application/Control Number: 18/475,687 Page 4 Art Unit: 1691 Application/Control Number: 18/475,687 Page 5 Art Unit: 1691 Application/Control Number: 18/475,687 Page 6 Art Unit: 1691 Application/Control Number: 18/475,687 Page 7 Art Unit: 1691 Application/Control Number: 18/475,687 Page 8 Art Unit: 1691 Application/Control Number: 18/475,687 Page 9 Art Unit: 1691 Application/Control Number: 18/475,687 Page 10 Art Unit: 1691