CTNF 18/456,798 CTNF 95735 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. Election/Restrictions 08-25-01 AIA Applicant’s election without traverse of Group II in the reply filed on 10/28/2025 is acknowledged. 08-06 AIA Claim s 1-6 and 10-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention , there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/28/2025 . Claims 7-9 and 14-16 are being examined on the merits . Claim Rejections - 35 USC § 112 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. Claim 8-9 and 15-16 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 “a culture product secreted from muscle cells by β -alanine” and this wording is confusing. A culture product is not defined and there can be various ways to interpret what that means. It is unclear how to obtain a culture product and to know what the product comprises of or does not comprise of. The metes and bounds of the limitation is indefinite. Additionally, β-alanine does not produce a muscle cell and so this wording “by β -alanine” is confusing. It appears the applicant is trying to claim a composition which is made by the process of contacting muscle cells with β-alanine or a salt thereof and collecting what is secreted from the muscle cells after contact with β-alanine or a salt thereof. This process is what should be claimed with wording already contained within the specifications in order to not introduce new matter. For compact prosecution the claims will be interpreted as such. 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. Claims 7-9 and 14-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for increasing COL1A1 component, Elastin synthesis, promotion of MFAP4, hyaluronic acid synthase and/or inhibition of HYAL1, MMP-1, Elastase, there is no evidence for inhibition of a wrinkle as claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The Applicant's attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. Nature of the invention: Claim 7 recites a method of inhibiting a wrinkle, comprising a step of administering an effective amount of β-alanine or a salt thereof to a subject. There is no required administration route nor dose required for the inhibition of a wrinkle. Merely claiming an effective amount requires optimization and experimenting to discover what amounts could work if any. The applicant shows β-alanine being effective as a component that can change gene expression of specific genes in dermal fibroblasts (see figures), however there is no evidence that wrinkles can be inhibited. Additionally, the applicant recites administering an effective amount of a culture product secreted from muscle cells by β-alanine or salt thereof (presumably meaning muscle cells cultured with β-alanine and their secreted components). The state of the prior art: The inhibition of wrinkles, generally speaking to the knowledge of those skilled in the art would be applying/administering a treatment that has shown efficacy in stopping wrinkles from forming through a targeted treatment plan. For instance Botox® (onabotulinumtoxinA) is a well-known and commonly used neurotoxin that reduces muscle activity by reducing nerve signals to muscles which can help smooth out wrinkles. Patients will receive injections at the site of wrinkles. This per se, is a common method for treating wrinkles and temporarily inhibits wrinkles from forming at this site of injection. This method is a common practice buy there are specific administration routes and dosage in units which are particular to the treatment, whereas with the instant case there is no such route of administration or dose known to inhibit a wrinkle. Using muscle cells cultured with β-alanine and their secreted components as a treatment for inhibiting wrinkles on the surface appears novel and so using muscle cells cultured components from the treatment of β-alanine as a means to inhibit wrinkles would require additional testing to see if this could actually be enabled. The applicant has only supplied evidence of cultured dermal fibroblasts being treated with the claimed components but there is no evidence or treatment which is to a wrinkle. The relative skill of those in the art: The relative skill of those in the art is high. The breadth of the claims. The scope of the claims is broad in the sense that there are no administration routes and dosage amount that tie the administration to the activity noted in the specifications. There is also no patient population that is specific for the treatment. The amount of direction or guidance presented: The specification directs persons of skill to methods for increasing COL1A1 component, Elastin synthesis, promotion of MFAP4, hyaluronic acid synthase and/or inhibition of HYAL1, MMP-1, Elastase etc. An increase or decrease in gene expression in cultured cells does not equate to wrinkle inhibition, even if some of those genes may be related in some way to wrinkle production. The applicant has not shown application of the composition to wrinkles or to presumably human’s (if this is an intended patient population) skin. Would a topical application work or can the administration of the β-alanine or salt thereof be taken orally? For instance, it would be expected that the oral administration would need to be much greater because of first pass metabolism as opposed to direct injection, or topical application. The presence or absence of working examples: The applicant has not tested the product on skin or wrinkles. Testing on cultured cells is much different than intact skin which is made up of many different cell types. It cannot be predicted if the increase/decrease of gene expression on cultured cells would equate to inhibition of wrinkles especially with no direction in administration route or dosage requirements. There are no working examples that actually show inhibition of wrinkles. The quantity of experimentation necessary: There may not necessarily need excessive amounts of experimentation necessary to determine if the composition can indeed inhibit wrinkles, however, the applicant has not provided any data or examples that would enable persons skilled in the art to use the invention for inhibiting wrinkles. The dosages and routes of administration would indeed need to be determined. Determining absorption, distribution, metabolism, excretion and pharmacokinetics would take time and effort. These types of tests cannot be predicted from mere cell cultures being treated with β-alanine. Therefore, in view of the Wands factors, as discussed above, Applicants failure to provide information sufficient to practice the claimed invention for inhibiting a wrinkle. 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 7 is rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Mikako Wantanabe et. al. (JP2002088097A) . Wantanabe discloses “Provided is β-alanine or a salt thereof and a method for producing the same. A method for producing N- (carboxymethyl) phenylalanyl-β-alanine or a salt thereof, which comprises reacting a phenylalanyl-β-alanine ester with a halogenoacetic acid ester in the presence of a base, followed by hydrolysis. The compound has an excellent effect of preventing or improving skin aging and an effect of suppressing hair growth” (see abstract). “An object of the present invention is to provide a compound useful as an external preparation for skin for preventing or improving skin aging such as wrinkles and suppressing hair growth” (see 0004). Wantanabe discloses that the compounds of the present invention had an excellent effect for improving skin (see 0034) and thus administration is apparent to have noticed an effect . Claim Rejections - 35 USC § 103 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. 07-20-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 8-9 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Ahmed H. Al-Qahtani (WO2015009325A1) and Yao-ming Huang et. al. (WO2016070152A1) . Al-Qahtani teaches skin care compositions which comprise of exosomes and cell culture medium conditioned by cells gown in two-dimensional culture (see abstract) and teaches wherein the cells which can be used to condition the medium are smooth muscle cells (see 0072). Al-Qahtani teaches that the composition is used for treating wrinkles (see Figure 3-4). Al-Qahtani teaches that the composition can positively influence skin collagen and elastin (see 0021). Huang’s general disclosure is to cell culture mediums to control for viability, growth and waste product accumulation (see abstract). Huan teaches cell culture mediums with beta-alanine as an additive or supplement (see abstract and 0066) which leads to increased cell growth (see 0086). Huan teaches that “a media formulation of the present invention that has been shown to have beneficial effects on metabolic balance, cell growth, and/or viability or on expression of polypeptide or protein comprise hypotaurine, Gamma-Aminobutyric Acid (GABA), and/or beta-alanine or the combination of choline with hypotaurine, GABA, and/or beta-alanine. One of ordinary skill in the art will understand that the media formulations of the present invention encompass both defined and non-defined media” (see 0165). Therefore it would have been obvious to persons having skill in the art before the effective filing date to use beta-alanine or the cell culture medium taught by Huan in the invention taught by Al-Qahtani because as Huan teaches this can have beneficial effects on metabolic balance, cell growth and viability. Regarding claims 14-16, pertaining to wherein the inhibition of the wrinkle is due to in dermal cells, a promotion of type I collagen component (COL1A1), inhibition of type I collagenase, promotion of elastin synthesis, promotion of microfibrillar associated protein (MFAP4), inhibition of elastase, promotion of hyaluronic acid synthase, or inhibition of hyaluronidase, would be inherent to the application of the prior art teaching of growing cultured muscle cells in cell culture medium substituted with beta-alanine as taught by Huan and Al-Qahtani and using the culture product especially the secreted exosomes for treating wrinkles. Al-Qahtani already teaches culture products of muscle cells for use in treating wrinkles and substituting Huan’s culture medium would have been prima facie obvious because one would want to increase viability and growth of the cultured cells. Additionally, Al-Qahtani teaches wherein the composition can positively influence production of collagen and elastin. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACOB ANDREW BOECKELMAN whose telephone number is (571)272-0043. The examiner can normally be reached Monday-Friday 8am-5pm. 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, Terry McKelvey can be reached at 571-272-0775 . 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. JACOB A BOECKELMAN Examiner, Art Unit 1655 /ANAND U DESAI/ Supervisory Patent Examiner, Art Unit 1655 Application/Control Number: 18/456,798 Page 2 Art Unit: 1655 Application/Control Number: 18/456,798 Page 3 Art Unit: 1655 Application/Control Number: 18/456,798 Page 4 Art Unit: 1655 Application/Control Number: 18/456,798 Page 5 Art Unit: 1655 Application/Control Number: 18/456,798 Page 6 Art Unit: 1655 Application/Control Number: 18/456,798 Page 7 Art Unit: 1655 Application/Control Number: 18/456,798 Page 8 Art Unit: 1655 Application/Control Number: 18/456,798 Page 9 Art Unit: 1655 Application/Control Number: 18/456,798 Page 10 Art Unit: 1655 Application/Control Number: 18/456,798 Page 11 Art Unit: 1655 Application/Control Number: 18/456,798 Page 12 Art Unit: 1655