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
Applicant’s election of Group I, claims 1 – 11 and species: L-arginine (NO doner), nicotinamide (counter NO agent) and SEQ ID NO: 4 (neurotoxin) in the reply filed on November 7, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1 – 20 are pending; claims 12 – 20 are withdrawn; claims 1 – 11 have been examined insofar as they read on the elected species.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120 is acknowledged.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The instant application filed on July 13, 2023 is a CIP of PCT/IL2022/050056, filed on January 13, 2022 and has the earliest provisional filing date of January 15, 2021. Application No. PCT/IL2022/050056, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Specifically, a composition comprising an NO donor, a counter NO agent and at least one neurotoxin (claims 8 – 9) and a composition comprising an NO donor, a counter NO agent and one or more inhibitors of hyaluronidase (claim 10). The prior document discloses a composition comprising an NO donor and counter NO agent is administered concurrent with administration of a neurotoxin. However, no single composition comprising all three components is disclosed or described.
In addition, claims 3 and 5 – 7 recite various ranges and ratios that do not find support in the prior filed application. Specifically, about 6% to about 12% (claim 3); about 0.25% to about 10%, 0.25% to about 4% (claim 5); about [3.5] to about 100:1, about 2.5:1 to about 40:1 (claim 6); and about 2.5:1 to about 40:1, about 3.5 to about 100:1, about 2.5:1 to about 5:1 (claim 7).
Therefore, these claims are not afforded the earliest claimed priority date but the actual filing date of the instant application (MPEP 211.05(I)(B)). For the sake of clarity, the claims are afforded the following filing dates:
Claims 1 – 2, 4 and 11, January 15, 2021; and
Claims 3 and 5 - 10, July 13, 2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 9, 2023 and November 26, 2024 are is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
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 1 – 11 are 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(s) 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.
Claims 1, 2, 4 and 9 recite some variation of “analogs or derivatives thereof.” These claims and those depending therefrom are considered genus claims that encompass a wide array of analogs and derivatives. The specification fails to set forth a representative number of examples in order to reasonably verify possession of such a potentially enormous number of analogs and/or derivatives.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that the claims are broad generics, with respect to all analogs or derivatives that might result from a single and specific agent, any agent that acts as a nitric oxide (NO) donor, and/or any agent that functions to “balance” effects of NO donors. The specification fails to describe what function is required to “balance effects” of any given NO donor. Initially, NO donors are a diverse and extensive class of compounds with varying structure and functions beyond the function of donating NO. The specification fails to describe all of these compounds and all of their “effects” in the skin. In paragraph 0004 of the published application, NO is disclosed to exhibit particular effects such as involvement in ultraviolet induced melanogenesis, promoting wound healing by cellular proliferation and angiogenesis, antimicrobial properties against micro-organisms, play an important role in T-cell mediated diseases of the skin, and having both pro and anti-apoptotic properties depending on its concentration, cell type, and availability of other substrates. However, the specification fails to describe these effects attributed to any NO donor, let any NO donor is analog or derivative. Additionally, the specification fails to disclose any particular effect of any NO donor that must be “balanced” by the counter NO agent. Further, the specification fails to describe any function of any counter NO agent that “balances” any non-specific effect of the NO donor in the skin. For example, whether the counter NO agents function to remove NO from the environment, prevents NO from forming, or merely have an activity contrary to those disclosed in paragraph 0004. In this regard, the specification fails to describe all of the possible effects of NO donors and any counter NO agent that acts in a nonspecific way such that one would know what compounds qualifies as a counter NO agent as claimed. The possible variations of NO donors and counter NO agents are limitless with potentially millions of types of compounds, let alone any analog or derivative thereof.
Regarding the phrase “a counter-NO agent which balances the effect of the NO-donor in the skin,” without reciting the particular structure, materials or steps that accomplish the function or achieve the result, all means or methods of resolving the problem may be encompassed by the claim. Unlimited functional claim limitations that extend to all means or methods of resolving a problem is not adequately supported by the instant specification. It is noted that a single claim reciting a functional outcome covering every conceivable means for achieving the stated result fails to satisfy the written description requirement because the specification discloses only those means known to the inventor, and is not commensurate in scope with the claim. (MPEP 2173.05(g)).
Regarding claim 10, the claim recites “one or more inhibitors of hyaluronidase.” The instant specification fails to identify any single compound as an inhibitor of hyaluronidase. Without reciting the particular structure, materials or steps that accomplish the function or achieve the result, all means or methods of resolving the problem may be encompassed by the claim. Unlimited functional claim limitations that extend to all means or methods of resolving a problem is not adequately supported by the instant specification. It is noted that a single claim reciting a functional outcome covering every conceivable means for achieving the stated result fails to satisfy the written description requirement because the specification discloses only those means known to the inventor, and is not commensurate in scope with the claim. (MPEP 2173.05(g)). Please note that claim 9 recites non-elected species, delineated by a function only without any disclosure of any particular structure, which suffer from the same lack of description stated herein.
The purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by them. A patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that the inventor invented the claimed invention. Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." The specification lacks sufficient variety of species of NO donors, counter NO agents, analogs and derivatives thereof to reflect this variance in the genus since the specification does not provide any examples of such a genus of compounds. Accordingly, the specification fails to provide adequate written description for the genus of NO donor, counter NO donor, analogs or derivatives thereof and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed had possession of the entire scope of the claimed invention Moreover, the specification neither describes the complete structure of a representative number of species, nor describes a representative number of species in terms of partial structure and relevant identifying characteristics. Absent of such teachings and guidance as to the structure and function of these compounds, the specification does not describe the claimed in such full, clear, concise and exact terms so as to indicate that Applicant had possession of these compounds at the time of filing of the present application.
Thus, the written description requirement has not been satisfied.
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.
Claims 1 – 3, 5 – 11 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 1 and its dependents are drawn to a composition comprising “a counter-NO agent which balances the effect of the NO-donor in the skin.” When claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. While the specification discloses examples of counter NO agents in paragraphs 0016 – 0018 of the published application, the specification fails to define what specific function or structure is require to meet the claimed limitation. Further, since the claim recites “analogs, or derivatives thereof,” it is unclear what functions are required to determine comparable analogs and what structures are required to determine its derivative. As such, the claim fails to clearly set forth what applicant regards as the invention (MPEP 2173.05(g)).
Claims 3 and 5 – 7 recite multiple broad recitations in combination with narrower statements of the range/limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. MPEP 2173.05(c).
Claim 9 recites “an inhibitor of SNARE complex formation and catecholamine release, an antagonism of muscular nicotinic acetylcholine receptor, an inhibitor of the release of the acetylcholine (ACh) neurotransmitter into the synapse,” and “an antagonist at the acetylcholine postsynaptic membrane receptor.” These phrases are not clearly defined by the claim language or specification. When claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. While the specification discloses a single example of each of these inhibitors and antagonists, the specification fails to define what specific function or structure is require to meet the claimed limitation. As such, the claim fails to clearly set forth what applicant regards as the invention (MPEP 2173.05(g)).
Claim 2 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of NO donors is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The claimed NO donors do not share a single structural similarity. For example, nitrites are nitrous acid esters; molsidomine is a heterocyclic aromatic; arginine has a typical amino acid core structure of carbon, amino group and carboxyl group; isosorbide mononitrate has a bicyclic furofuran structure; mannitol hexanitrate is an ester derivative of a sugar; minoxidil is a pyrimidine N-oxide. Moreover, the various recited compounds do not have a recognized shared physical class, chemical class or art recognized class and are not considered to be functionally equivalent compounds.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 102
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.
Claims 1 – 7 and 10 – 11 are rejected under 35 U.S.C. 102a1 and 102a2 as being anticipated by Stofman et al. (US 2013/0210867) as evidenced by Okorukwu et al. (2003).
Regarding claim 1 -2 and 4, Stofman teaches topical compositions for application to skin, comprising L-arginine (NO donor), nicotinamide (counter NO agent) and pharmaceutical salts and derivatives (abstract, 0008, 0029, example 3, claims).
Regarding claim 3, the L-arginine may be included in any effective amount such as 1 - 100%, 10 - 95%, 20 - 95%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28% 29% 30% (0021).
Regarding claim 5, the nicotinamide may be included 1n any effective amount such as 0.001 - 100%, 0.001 - 1%, 0.005 - 0.2%, 0.09% - 3%, 2% - 5% (0024).
Regarding claims 6 and 7, the claimed ratios fall within the disclosed ranges of each L-arginine and nicotinamide (0021, 0024).
Regarding claim 10, the composition further includes ascorbic acid (an inhibitor of hyaluronidase as evidenced by Okorukwu) and glycerin (used by applicant, examples) (0017, example 3).
Regarding claim 11, the form may be a gel, ointment, foam, spray, cream, salve, lotion, liquid, emulsion or liposomal solution (0030).
The reference anticipates the claimed subject matter.
Claim 1 – 2, 4 and 8 – 11 are rejected under 35 U.S.C. 102a1 and 102a2 as being anticipated by Santhanam et al. (US 2018/0353407) as evidenced by Ron et al. (US 2023/0355493) and Okorukwu et al. (2003).
Regarding claims 1 – 2 and 4, Santhanam teaches topical compositions for application to skin comprising arginine (NO donor), (niacinamide (nicotinamide, counter NO agent) and pharmaceutical salts and derivatives (abstract, 0079).
Regarding claims 8 – 9, the composition may further include Pentapeptide-3, or SEQ ID NO: 4, KTTKS (see Ron et al., 0085).
Regarding claim 10, the composition may further include ascorbic acid or glycerin (inhibitors of hyaluronidase (see Okorukwu and applicant’s examples) (101, 105).
Regarding claim 11, the form may be a lotion, cream, serum, spray, ointment, essence, gel, paste, mask, stick or foam (0129).
The reference anticipates the claimed subject matter.
Double Patenting
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.
Claims 1 – 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3 – 8, 10 of copending Application No. 18/221,515 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they claim the same compositions.
The co-pending applicant claims a topical composition comprising at least 6% 1-arginine or cosmetically or pharmaceutically acceptable salts, isomers, analogs, or derivatives thereof (claim 1); wherein the concentration of 1-arginine is selected from the group consisting of about 6% to about 25%, about 6% to about 12%, about 6% to about 8%, about 8% to about 10%, about 10% to about 14%, about 14% to about 18%, and about 18% to about 25% (claim 3); further comprises nicotinamide, a salt, an isomer, an analog, or a derivative thereof (claim 4); at a concentration of about 0.25% to about 10%, about 0.25% to about 4%, about 1% to about 2%, about 2% to about 4%, about 4% to about 6%, about 6% to about 8%, or about 8% to about 10% (claim 5); wherein the ratio between the arginine and nicotinamide in the topical composition is selected from the group consisting of about 3:5 to about 100:1, about 2.5:1 to about 40:1, about 1:2 to about 8:1, about 1:2 to about 1:1, about 1:1 to about 2:1, about 2:1 to about 4:1, and about 4:1 to about 8:1 (claim 6); further includes at least one neurotoxin-mimetic agent selected from the group consisting of an inhibitor of SNARE complex formation and catecholamine release, an antagonism of muscular nicotinic acetylcholine receptor, an inhibitor of the release of the acetylcholine (ACh) neurotransmitter into the synapse, acetyl hexapeptide-3, the peptide AC-gly glu-met-gln-arg-arg-NH2, Tripeptide-3, beta-Ala-Pro-Dab-NH-benzyl×2AcOH, acetyl hexapeptide-1, an antagonist at the acetylcholine postsynaptic membrane receptor, Pentapeptide-3, Lys-Thr-Thr-Lys-Ser; and derivatives, analogs or salts thereof (claim 8); and is in a form selected from the group consisting of a liquid, a solution, an emulsion, a lotion, a cream, a gel, a foam, a stick, a lipstick, a mask, and a serum (claim 10).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 – 7 and 10 – 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 34 – 35 and 37 – 38 of copending Application No. 18/272,163 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are drawn to the same composition.
The reference application claims a topical composition for application to the skin, comprising l-arginine and nicotinamide, or cosmetically or pharmaceutically acceptable salts, isomers, analogs and derivatives thereof; wherein the concentration of l-arginine is selected from the group consisting of about 6% to about 25%, about 6% to about 8%, about 8% to about 10%, about 10% to about 14%, about 14% to about 18%, and about 18% to about 25%; and wherein the concentration of nicotinamide is selected from the group consisting of about 1% to about 2%, about 2% to about 4%, about 4% to about 6%, about 6% to about 8%, and about 8% to about 10% (claim 34); has a ratio between the arginine and nicotinamide in the topical composition is selected from the group consisting of about 4:1 to about 6:1, about 6:1 to about 8:1, about 8:1 to about 10:1, about 10:1 to about 14:1, about 8:1 to about 10:1, about 14:1 to about 18:1, and about 18:1 to about 25:1 (claim 35); includes an agent that slows down or eliminates the enzymatic degradation of injected hyaluronic acid, or inhibitor of hyaluronidase (claim 37); and is in a form selected from the group consisting of a liquid, a solution, an emulsion, a lotion, a cream, a gel, a foam, a stick, a lipstick, a mask and a serum (claim 38).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
No claims are allowed.
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/RUTH A DAVIS/ Primary Examiner, Art Unit 1699