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 .
Status of Claims
Claims 1-5 and 11-25 are pending in the instant application.
Claims 6-10 have been canceled.
Priority
Acknowledgement is made of Applicant’s claim for foreign priority based on the KR10-2023-0166404 application filed in the Republic of Korea on November 27th, 2023.
Information Disclosure Statement
Applicant has submitted no Information Disclosure Statement (IDS) with this application. Applicant is reminded per 37 CFR 1.56, “Each individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability …”
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which Applicant may become aware of in the specification.
Drawings
The drawings are objected to because text in Figure 1 is illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 12, 14, and 25 are objected to because of the following informalities:
Claim 12 recites the limitation “A topical composition for preventing or ameliorating wet age-related macular degeneration comprising nicotinamide, or derivatives thereof, as an active ingredient.” Claim 14 recites “wherein the derivatives of nicotinamide is a compound of Formula 2, or Formula 3”. Recitation of the plural “derivatives” in Claim 12 implies multiple derivatives must be present. Claim 14, however, suggests a choice between a compound of Formula 2 and Formula 3 as a derivative of nicotinamide. This objection can be overcome by changing “derivatives” in Claim 12 to “a derivative” and changing “derivatives” in Claim 14 to “derivative”.
Claim 25 recites in the first line “wherein the wherein”. “The wherein” is redundant. This objection can be overcome by removing “the wherein”.
Appropriate correction is required.
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, 3-5, 11-12, 14-17, and 23-25 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 a composition comprising nicotinamide or a derivative thereof wherein the derivative is Formula 2 or Formula 3, does not reasonably provide enablement for a composition comprising any derivative of nicotinamide. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a composition comprising nicotinamide or a derivative thereof.
Breadth of the invention:
The scope of the claimed invention is very broad. The instant specification at Page 6, Paragraph [0024] defines “derivatives of nicotinamide” as “compounds that are formed by modifying a portion of the molecular structure of nicotinamide.” This includes a myriad of compounds readily envisaged by a person having ordinary skill in the art.
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
Applicant sufficiently discloses compositions comprising nicotinamide or a derivative of nicotinamide wherein the derivative is of Formula 2 or Formula 3. No examples have been provided, however, of compositions comprising derivatives of nicotinamide that are not of Formula 2 or Formula 3. Sufficient guidance has not been provided such that a person having ordinary skill in the art would readily understand which derivatives beyond Formula 2 or Formula 3 are suitable for use within the context of the instant invention, nor would it be readily understood based on the instant disclosure the benefits of selecting derivatives that are not Formula 2 or Formula 3.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP 608.01(p).
MPEP § 2164.01 (a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F. 2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for the breadth of compositions instantly claimed.
Claims 18-24 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 treating wet age-related macular degeneration comprising administering nicotinamide, or a derivative that is Formula 2 or Formula 3, does not reasonably provide enablement for prevention of wet age-related macular degeneration or for treatment of wet age-related macular degeneration comprising administering any derivative of nicotinamide. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a method of preventing or treating wet age-related macular degeneration comprising administering nicotinamide or a derivative thereof.
Breadth of the invention:
The scope of the claimed invention is very broad. The instant specification at Page 6, Paragraph [0024] defines “derivatives of nicotinamide” as “compounds that are formed by modifying a portion of the molecular structure of nicotinamide.” This includes a myriad of compounds readily envisaged by a person having ordinary skill in the art.
State of the prior art and predictability in the art:
With respect to prevention of age-related macular degeneration, Di Carlo et. al. (“Prevention of the Onset of Age-Related Macular Degeneration”, Journal of Clinical Medicine, 2021; hereinafter referred to as Di Carlo) represents the state of the prior art.
At the Abstract, Di Carlo states, “The current therapeutic options are only partially able to slow down the natural course of the disease, without being capable of stopping its progression. Therefore, better understanding of the possibilities to prevent the onset of the disease is needed.”
At Page 4, Fourth Paragraph, Di Carlo teaches nutritional supplementation has been shown to prevent progression of age-related macular degeneration, no data exists supporting the possibility to prevent the onset of age-related macular degeneration. At page 8, Second Paragraph, Di Carlo teaches increase in oxidative resistance as a result of moderate physical activity “might lead to AMD prevention.”
Taken together, Di Carlo establishes that the prevention of age-related macular degeneration is not known in the art, and efforts thereof are highly speculative.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
Applicant discloses working examples of administering nicotinamide, and the derivatives of Formula 2 and Formula 3 in the instant specification. No examples of administration of any derivative that is not Formula 2 or Formula 3 have been provided. No examples supporting the claim of prevention have been provided. Sufficient guidance has not been provided such that a person having ordinary skill in the art would readily understand which derivatives beyond Formula 2 or Formula 3 are suitable for use within the context of the instant invention, nor would it be readily understood based on the instant disclosure the benefits of selecting derivatives that are not Formula 2 or Formula 3.
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. As referenced above, a person having ordinary skill in the art would need to not only identify suitable derivatives for use within the context of the instant invention, but also to evaluate the efficacy of these derivatives in treating wet age-related macular degeneration, with no assurance of success.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
The specification fails to provide enough support for the broadly claimed prevention of wet age-related macular degeneration or for the treatment thereof with derivatives that are not of Formula 2 or Formula 3.
Genentech Inc. v Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person having ordinary skill in the art would have to engage in undue experimentation to determine suitable derivatives of nicotinamide for the treatment of wet age-related macular degeneration, with no assurance of success.
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 3, 14, and 20 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.
Claims 3, 14, and 20 are rendered indefinite due to the recitation of a compound of Formula 3 wherein Formula 3 is:
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This renders the claim indefinite because Formula 3 is recited as a compound, but the structure is not charge-neutral. Based on the instantly recited limitations, a person having ordinary skill in the art would not be able to reasonably ascertain the metes and bounds of a compound of Formula 3, as a counterion is not recited.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 4-5, and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Richer (WO 2020/185515 A1; hereinafter referred to as Richer).
For clarity of the record, the examiner notes that recitation of “for preventing or treating wet age-related macular degeneration” is a statement of intended use. Per MPEP 2111.02, II., “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020).” Therefore, in the instant case, Claim 1 is drawn to a pharmaceutical or food composition comprising nicotinamide or a derivative thereof as an active ingredient.
At Page 8, Paragraph [0035], Richer teaches niacinamide is another name for nicotinamide.
At Page 3, Paragraph [0013], Richer states “The resent disclosure enhances the current “Standard of Care” (e.g., the existing commercial 750 mg AREDS II gel capsules or the “AREDS II formulation” or “AREDS II”) and is based on the discovery and development of an enhanced AREDS II formulation, which when combined with widely available and inexpensive low dose nutrients, can more effectively slow the progression of AMD.” Further, at Page 8, Paragraph [0035], Richer teaches the enhanced AREDS II formulation includes niacinamide.
At Figure 1B, Richer teaches a gel capsule formulation including 25 mg of niacinamide.
Taken together, Richer teaches a composition formulated as a gel capsule comprising nicotinamide. This reads on the limitation of Claim 11, as Richer teaches the aforementioned composition formulated as a gel.
Claims 1-2, 4-5, 12-13, and 15-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ashkani Esfahani et. al. (“Topical Nicotinamide Improves Tissue Regeneration in Excisional Full-Thickness Skin Wounds: A Stereological and Pathological Study”; hereinafter referred to as Ashkani Esfahani).
At the first page, at Objectives, Ashkani Esfahani teaches the goal of the study is to determine the effects of topical administration of nicotinamide. Additionally, at the First Page, under “3.1 Preparation of Nicotinamide Gel”, Ashkani Esfahani teaches the production of a gel containing nicotinamide. At Page 2, under “3.2 Animals and Excision of Wound Model”, Ashkani Esfahani teaches topical administration of this gel.
Claims 1, 3-5, 11-12, and 14-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Deren-Lewis et. al. (WO 2015/066382 A1; hereinafter referred to as Derren-Lewis).
At the Abstract, Derren-Lewis teaches compositions containing nicotinamide riboside (NR). At Page 6, Paragraph [0031], Derren-Lewis teaches the structure of nicotinamide riboside is:
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This is the same structure as provided as Formula 3 as recited at Claims 3 and 14.
Regarding Claims 1, 3-5, and 11, Derren-Lewis teaches at Page 8, Paragraph [0042] oral formulations comprising nicotinamide riboside as a pharmaceutical or nutraceutical composition. At Page 11, Paragraph [0054], formulations are taught to include gels, and at Paragraph [055], gels include gums.
Regarding Claims 12 and 14-17, Derren-Lewis teaches at Page 8, Paragraph [0041] topical compositions comprising nicotinamide riboside. At Page 10, Paragraph [0051], it is taught that the topical pharmaceutical compositions can be in the form of an ointment.
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.
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.
Claims 18-19, 21-23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Richer (WO 2020/185515 A1; hereinafter referred to as Richer) in view of Westenskow (“Nicotinamide: a novel treatment for age-related macular degeneration?”, Stem Cell Investigation, 2017; hereinafter referred to as Westenskow).
As stated above, at Page 8, Paragraph [0035], Richer teaches niacinamide is another name for nicotinamide.
At Page 3, Paragraph [0013], Richer states “The resent disclosure enhances the current “Standard of Care” (e.g., the existing commercial 750 mg AREDS II gel capsules or the “AREDS II formulation” or “AREDS II”) and is based on the discovery and development of an enhanced AREDS II formulation, which when combined with widely available and inexpensive low dose nutrients, can more effectively slow the progression of AMD.” Further, at Page 8, Paragraph [0035], Richer teaches the enhanced AREDS II formulation includes niacinamide.
More directly, at Page 1, Paragraph [002], Richer teaches the instant disclosure relates to prevention and treatment of age-related macular degeneration (AMD).
Regarding Claim 21, at Page 15, Paragraph [0062], Richer teaches the aforementioned formulation inhibits angiogenesis. At Figure 1B, niacinamide is taught to have senolytic synergy with resveratrol. At Page 12, Paragraph [0050], resveratrol is taught to inhibit angiogenesis.
Regarding Claim 22, at Page 5, Paragraph [0049], Richer teaches the aforementioned formulation augments anti-neovascular properties, critical for treating AMD associated with scarring.
Regarding Claim 25, Richer teaches at Page 5, Paragraph [0025] that the aforementioned formulation can be administered in daily doses formulated as capsules.
Richer is silent with respect to treatment of wet age-related macular degeneration.
Westenskow states at Page 5, First Paragraph of Second Column, “nicotinamide might be best employed as a therapy for wet AMD”.
Applying KSR exemplary rationale G, it would have been obvious for a person having ordinary skill in the art to attempt treating wet age-related macular degeneration, as it was known in the prior art based on the teachings of Richer, above, that nicotinamide is useful in treating age-related macular degeneration, supported by the teaching of Westenskow that nicotinamide is well-suited for treating wet age-related macular degeneration.
Taken together, Claims 18-19, 21-23, and 25 would have been practiced with reasonable expectation of success.
Conclusion
Claims 1-5 and 11-25 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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/D.J.B./Examiner, Art Unit 1624
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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