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 – Status of the claims
Applicant’s election without traverse of the species of SEQ ID NO. 40 in the reply filed on October 10, 2025, is acknowledged.
Claims 1-13 and 15-18 are pending in the instant application; claim 4 is withdrawn as being directed to a non-elected species (a chemically derivatized peptide); and claims 1-3, 5-13, and 15-18, are the subject of the Office Action below.
Priority
This patent application claims priority from PCT Application No. PCT/EP2021/067203 filed June 23, 2021 which claims priority from European Patent Application No. 20382617.7 filed July 9, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 3, 2023, has been considered where initialed by the Examiner. The submission is in compliance with the provisions of 37 CFR 1.97.
Claim Rejections - 35 USC § 112
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 13 and 18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 13 is indefinite for the recitation of the phrase “dietary supplement” because one of ordinary skill in the art could not reasonably determine the metes and bounds of this limitation. Specifically, the recitation of this limitation is directed solely to broad and vague functional-descriptive matter without any specific or reasonable relation to chemical or compositional structure. The specification mentions this term on five particular instance, but provide neither a definition or reasonable examples for context. For example, it is not clear if water would be included or excluded, if fillers would meet this limitation even if they are devoid of nutritional content, or in what way something is considered “dietary”. For the purposes of examination, this limitation will include water.
Claim Rejections - 35 USC § 103
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.
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.
Claims 1-3, 11-13, 15, 17, and 18 are obvious over Bodington in view of Ramaiah, Zarate, and Cilia:
Claims 1-3, 11-13, 15, 17 and 18, is/are rejected under 35 U.S.C. 103 as being unpatentable over Bordington, U.S. Patent Publication No. 2014/0004130, published on January 2, 2014, in view of Ramaiah, U.S. Patent No. 9,457,064, issued on October 4, 2016, Zarate et al., 2009 International Nuclear Atlantic Conference, ISBN: 978-85-99141-03-8, and Cilia et al., J. Complementary and Integrative Med., 2018, pages 1-10 (cited in the IDS).
Applicants invention is directed towards compositions and methods for treating vitiligo in patients using certain peptide active agents in pharmaceutical formulations, such as, lotions and creams.
Claim 1 is directed towards a pharmaceutical composition comprising:
(a) a melanoma inhibitory activity protein (MIA) inhibitor peptide which has a sequence selected from the group consisting of SEQ ID NOs: 12-20 and 27-49, or is a derivative thereof, wherein derivative means that the peptide is acctylated at the N-terminus and/or amidated at the C-terminus;
(b) snail secretion; and
(c) at least one pharmaceutically acceptable excipient.
Claim 15 is directed towards a method for the prevention or treatment of vitiligo in a patient in need thereof comprising the step of applying a therapeutically effective amount of the composition according to any one of claims 1, 2 or 3.
Claims 2 and 3 further limit claim 1 to sequences including SEQ ID NO: 40. Claim 11 limits claim 1 to compositions suitable for topical use. Claim 12 is directed towards creams and gels.
Similar to the claimed invention, Bordington teaches modified peptides for treating patients suffering vitiligo, wherein the modified peptides serve as inhibitors to MIA:
“Peptides, modified peptides and antibody or antibody fragment, which inhibit the activity of MIA (Melanoma Inhibitory Activity), for detecting, preventing and curing vitiligo are disclosed.”
Bodington, Abstract.
Bodington also teaches the underlying mechanism of the peptides disclosed therein:
“[0024] MIA inhibitors represent a targeted therapy for non segmental vitiligo. Due to their specific binding to MIA, these molecules do not raise the side-effects commonly reported for actual therapies as cutaneous atrophy, pruritus, toxicity or oncogenetic potential.
[0026] Moreover, the inhibition of MIA, by avoiding damages towards melanocytes leads to re-pigmentation defiant of treated the anatomic area, thus implementing the treatment of difficult areas such as hands and feet.
[0027] The therapy-resistant site for vitiligo, such as hands and feet, are said to be due to the lack of melanocytes reservoir in these sites; our data shows a high presence of MIA against the melanocytes of these sites, probably due the continuous friction of these Zones. Inhibitors of MIA, by removing all molecules of MIA, successfully treat these areas.
[0028] Therefore peptides, modified peptides and antibody or antibody fragment inhibiting the activity of MIA can be used for treating vitiligo by inducing re-pigmentation.
[0029] Said compounds can also be used useful as early markers of vitiligo development and as tools for follow-up of vitiligo patients and also for preventing the appearance of vitiliginous patches.
[0030] Said compounds can also be used for making the already known therapies more effective. Is therefore object of the present invention the use of at least one peptide with sequence ID No. 1 to 49 for detecting, preventing and curing vitiligo.
[0031] In a further object of the present invention, in said peptides one or more amino acid is Substituted by a natural amino acid or a non-natural amino acid.
[0032] In a further object of the present invention, the non natural amino acid is a modified natural amino acid wherein the modification is a Substitution of one or more atoms with a functional group comprising 1 to 12 atoms selected from C, H, N, S, O, P, F, Cl, Br, I, Se.
[0051] Are further objects of the present invention the phar
maceutical composition comprising at least one of the above
peptides and/or at least one of the above anti-MIA antibodies
solubilized and/or vehicle by pharmaceutically acceptable
excipients and/or diluents.”
Bodington, page 2, paragraphs 0023-0032, and 0051.
Bodington also teaches a peptide with a sequence identical to the elected sequence of SEQ ID NO. 40 of the instant application, which also has the same sequence identifier number:
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Bodington, paragraph 0045.
Bodington also claims methods for treating vitiligo and pharmaceutical compositions, comprising peptides and excipients, for doing the same (see claims 1 and 11).
Although Bodington teaches and claims the aforementioned methods and compositions, he does not teach the claimed pharmaceutical composition of claim 1, such as a lotion, having a snail secretion. However, one of ordinary skill in the art would have had a reasonable expectation of success in utilizing snail secretion in a lotion because: 1) peptide-based therapeutics are known to be an advantage in the treatment of the skin in patients affected with vitiligo via a topical application such as a lotion; and 2) snail secretions have many beneficial effects to the health and well-being of the human skin when applied in lotions carrying and active agent. For example, see Ramaiah, Zarate, and Cilia.
Ramaiah teaches the use of certain peptides for the treatment of vitiligo in a pharmaceutical lotion:
“Synergistic therapies for the treatment of vitiligo are provided, in which basic fibroblast growth factor peptide(s) lotion was developed as a new mode of therapy for the treatment of vitiligo. It went through various phases of successful clinical trials in India and is marketed by the drug controller general (India). It is effective in 80% of stable and segmental vitiligo. Data are provided which demonstrate that combinatorial treatment of vitiligo by local application of bFGF peptide(s) lotions in association with psoralens and UV-A, or steroids or surgical procedures, produce a synergistic response in which the rate of repigmentation increases synergistically and more efficacious results are obtained than with any one of them alone. Any combinatorial therapy comprising the local application of bFGF peptide(s) lotion on the vitiligo patch in combination with any other therapies for the treatment of vitiligo also may act synergistically.”
Ramaiah, Abstract (emphasis added).
Zarate teaches that snail secretions are beneficial in the use of cosmetics and topical applications to the skin, and a method for providing the extract/secretion free of microbial contamination:
“The snail (Helix aspersa muller) secretion or its filtrating is an emerging raw material utilized to elaborate different cosmetics products in Chile. This secretion has properties such as regeneration and healing of tissues, elimination of spots in the body, among others. All of them are associated to some of its own components, like the glycolic acid and alantoine. However, working ·with the secretion has not been free of complications nor sanitary difficulties due to the great manipulation to which it is exposed to, making it vulnerable to microbiological contaminations and causing it not to qualify according to the sanitary criteria stated by cosmetics laboratories, resulting in the material loss for the producer.”
Zarate, Abstract (emphasis added).
Cilia is similar in that they teach dermatological compositions with multiple skin health benefits that have snail secretions, including their antioxidant components and healing capabilities:
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Cilia, page 2, second paragraph.
Accordingly, at the time the invention was filed, one of ordinary skill in the art would have determined the claimed invention to be prima facie obvious.
Claims are further rejected in view of Mancini, Comune and Narsireddy:
Claims 5-10, 16 and 17, are rejected under 35 U.S.C. 103 as being unpatentable over Bordington, U.S. Patent Publication No. 2014/0004130, published on January 2, 2014, in view of Ramaiah, U.S. Patent No. 9,457,064, issued on October 4, 2016, Zarate et al., 2009 International Nuclear Atlantic Conference, ISBN: 978-85-99141-03-8, and Cilia et al., J. Complementary and Integrative Med., 2018, pages 1-10 (cited in the IDS) as applied to claims 1-3, 11-13, 15, 17 and 18 above, in further view of Mancini et al., WO 2015/075116, published on May 28, 2015; Comune et al., Journal of Controlled Release, 262 (2017) 58-71; and Narsireddy et al., International Journal of Pharmaceutics, 471 (2014) 421-429.
The limitations of claims 1-3, 11-13, 15, 17 and 18, as well as the teachings of the prior art, are found in the rejection above and are hereby incorporated to the instant rection.
Claim 5 further limits claim 1 by requiring that the peptide be encapsulated within a carrier nanoparticle, or encapsulated within a carrier nanoparticle. Claim 6 requires the surface of the carrier nanoparticle to be derivatized with a MC1 receptor agonist. Claim 7 further limits claim 5 by linking the peptide to a gold nanoparticle. Claims 8-10 are directed to different weight percentages of the peptides and snail secretion.
Although the art cited in the previous rejection does not explicitly teach the aforementioned limitations, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the invention with claimed nanoparticle and various amounts because: 1) each of Mancini and Comune and demonstrate certain peptide-derivatized nanoparticles (PLGA and gold) having various densities/amounts of peptide; and 2) Narsireddy teaches use of peptide transdermal therapies in conjunction with phototherapy for selective controlled release in target specific areas of the skin.
Mancini discloses targeted delivery of skin whitening compounds facilitated by MC1 agonist peptides:
One of the possible combinations of the peptide of formula (I) and the skin whitening compound is by forming a capsule, that may be a microcapsule or a nanocapsule, which encapsulates the skin whitening agent and wherein the peptide of formula (I) is coupled to the outer surface of the capsule which allows targeting the MCR1 receptors on the melanocyte, i.e. the inventors have developed targeted capsules for the delivery of skin whitening compounds, which improve the whitening effect of the skin whitening compounds. These are surprising results as the peptide of formula (I) is a MC1 receptor agonist, and not a MC1 R receptor inhibitor which are normally used in the art for the effect of improving the activity of the tyrosinase inhibitor, i.e. skin whitening compound, in the treatment of dark spots on the skin, e.g. Melanostatine ®5 and Sepiwhite MSH.
Mancini, page 3, and materials such as PLGA for construction of the nanoparticles.
Comune teaches the use of gold nanoparticles derivatized with therapeutic peptides through transdermal administration:
“Topical therapies that combine antimicrobial and pro-regenerative effects are of great potential in the context of skin wound healing [1]. Antimicrobial peptides (AMPs) act as a first line of defense in the human body against bacteria, virus and fungi [2,3], and some of them modulate regeneration processes [4].”
Comune, page 58; and:
Here, we investigated the wound healing potential of LL37-conjugated NPs both in vitro (migration of keratinocytes) and in vivo (skin wound healing). These NPs have a gold (Au) core and a hydrophilic cationic LL37 peptide shell. We have selected Au NPs because it is relatively easy the modification of their properties (e.g. size), the immobilization of high concentrations of AMPs per surface area [13], and they have a biomedical track [22]. LL37-conjugated NPs were prepared by a one step procedure [13]. Initially, the physico-chemical properties of LL37-Au NPs were characterized. To show the unique properties of LL37-Au NPs we have evaluated their pro-migratory properties against keratinocytes, an important player in the context of skin healing, and evaluated their mechanism relatively to LL37 peptide. Finally, we have evaluated in vivo the regenerative potential of LL37 and LL37-Au NPs in a splinted mouse full thickness excisional model. Overall our results indicate that LL37-conjugated NPs have enhanced wound-healing properties than LL37 peptide because they prolong in time the biological activity of the peptide.
Comune, page 59.
Narsireddy teaches photodynamic therapy with peptide therapeutics for selective targeting:
In targeted photodynamic therapy (tPDT), photosensitizers (PS) are targeted to disease tissue to reduce the dosage of PS and in addition to reduce the photo damage to the non-target tissue. We synthesized iron oxide nanoparticles (NP) armored with tumor targeting peptide and PS for targeted PDT. Chitosan covered Fe3O4 NPs (30 nm) were deposited with gold NPs to generate two distinct chemical surfaces. To the gold particles PS was attached with a lipoic acid linker. Human epidermal growth factor receptor (hEGFR)-specific peptide was also attached to the same particles via a nickel-nitrilotriacetic acid linker attached to the chitosan. Using these nanoparticles, peptide specific uptake and PDT mediated cell death of the SK-OV-3 cells (Her2+ positive cells) were demonstrated by confocal microscopy, T2 imaging and viability assays. Peptide mediated preferential distribution of these NPs into tumor tissue was also shown in a xenograft tumor model. After one intravenous injection and one PDT dose, peptide bound NPs retarded tumor growth significantly compared to dark controls or treatments with NPs without peptide. The tumor retardation by targeted NPs was achieved at a PS concentration of 3.9 nmol/animal, whereas similar effect was seen with free PS at 220 nmol/animal. Therapeutic potential of these peptide containing NPs would be a useful in targeted PDT and in imaging the target tissue.
Narsireddy, Abstract
Accordingly, the claimed invention was prima facie obvious at the time it was invented.
Conclusion and Inquiries
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/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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