DETAILED ACTION
Examiner acknowledges receipt of the reply filed 7/07/2026, in response to the restriction requirement mailed 5/07/2026.
Claims 1-10 are pending and being examined on the merits in this office 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 .
Priority
The filing receipt dated 5/03/2024 has the following information:
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Election/Restrictions
Applicant’s election of Group 1 (claims 1-8) without traverse in the reply filed on 7/07/2026 is acknowledged.
Upon further consideration, the restriction between groups 1-3, as set forth in the office action mailed 5/07/2026, is withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Examiner acknowledges election of the following species:
PDSP: SEQ ID NO: 3
Buffer: histidine buffer
Claims 1-10 read on the elected species. Election was made without traverse in the reply filed on 7/07/2026.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure relates,” “The disclosure defined by this invention,” “The disclosure describes,” etc. Here, the abstract states “The present invention relates to”.
Claim Objections
Claims 1-8 and 10 are objected to because of the following informalities:
Claim 1 should be amended to recite “comprising[[:]] a PEDF-derived short peptide (PDSP), a stabilizer, and a buffer;[[,]] wherein the composition is in a liquid form, wherein a pH of the composition is in a range of 4-9;[[,]] wherein the stabilizer is a copolymer of vinylpyrrolidone and vinyl acetate; and[[,]] wherein the buffer is a citric acid buffering system…”
The acronym PEDF should be written out in full name in the first order of appearance in the claims.
Claim 2 should be amended to recite “selected from the group consisting of an osmolarity regulator, a bacteriostatic agent, and a suspension agent, or a combination thereof”.
Claim 3 should be amended to recite “combination thereof; and[[,]] wherein a concentration”.
Claims 4 and 6 should be amended to recite “combination thereof; and[[,]] wherein a concentration”.
Claim 5 should be amended to recite “range of 6-8; and[[,]] wherein”.
Claim 7 should be amended to recite “w/v[[, ]].”.
Claim 8 should be amended to recite “200mM[[, ]].”.
Claim 10 should be amended to recite “method of . aging, liver cirrhosis, and eye disease, or and [[a]] combination thereof”. Alternatively, the preamble should recite “a method of treating or preventing a disease”.
Appropriate correction is required.
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 1-5 and 7-10 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.
The metes and bounds of the claim term “PEDF-derived” are indefinite. The Derive, Free Online Medical Dictionary (accessed at URL medical-dictionary.thefreedictionary.com/derive, 2017) defines the term "derive" as to produce or obtain (a peptide in this instance) from another substance by chemical reaction. The term "derive" is generally defined as to obtain or receive from a source. The source of the PEDF is unclear- as to what organism (human, bovine, whale, avian) or variant thereof. Further the degree to which the claimed peptide is “derived” from PEDF is unclear. For instance, a peptide could be a fragment with 100% identity to a sequence from a PEDF protein or merely 10% sequence similarity. A peptide could be 5 amino acids total length yet only have 2 consecutive amino acids of a PEDF protein and the
another 3 non-analogous amino acids to give a total length of 5 amino acids.
Claim clarification is required for the term “PEDF-derived”.
Because claims 2-5 and 7-10 depend from indefinite claim 1 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b).
Claim 10 recites the limitation "the treatment". There is insufficient antecedent basis for this limitation in the claim.
The term “muscle damage” in claim 10 is a relative term which renders the claim indefinite. The term “muscle damage” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Specifically, the metes and bounds of the claim term and what constitutes “damage” is unclear from the claim and specification. For instance, muscle damage could encompass a sore back, blunt force trauma, or a muscle tear. It is unclear as to what conditions fall within the claim scope and those outside of the claim scope.
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 1-5 and 7-10 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.
The courts have stated:
“To fulfill the written description requirement, 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." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gostelli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618.
In the instant case, claim 1 is directed to a composition comprising: a PEDF-derived short peptide (PDSP), a stabilizer, and a buffer, wherein the composition is in a liquid form, wherein a pH of the composition is in a range of 4-9, wherein the stabilizer is a copolymer of vinylpyrrolidone and vinyl acetate, wherein the buffer is a citric acid buffering system, a phosphate buffering system, a boric acid buffering system, a histidine buffering system, or a combination thereof. Claim 6 recites the composition according to claim 1, wherein the PDSP is selected from SEQ ID NO: 1, 2, 3, 5, 6, 8, 9, or a combination thereof, wherein a concentration of PDSP is 0.001%-5% w/v.
Claim 10 is directed to a method for the treatment and/or prevention of a disease, comprising administering to a subject in need thereof the composition according to claim 1, wherein the disease is selected from the group consisting of muscle damage, alopecia and/or hair depigmentation, osteoarthritis, skin aging, liver cirrhosis, eye disease, and a combination thereof.
The specification states: the term "PEDF-derived short peptide (PDSP)" refers to peptides derived from PEDF and having varying numbers of amino acid residues, such as peptides having 5 to 40 amino acid residues (para [0009]). Table 1 discloses specific peptides SEQ ID NOs:1-9. SEQ ID NOs 1-2, 5, 6, 5, and 9 share an overlapping core sequence (bold font). Table 1:
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Examples 1-8 teach compositions comprising SEQ ID NO:3, PVPV A64, and histidine buffer. Examples 11-15 teach compositions comprising SEQ ID NO:3, PVPV A64, and citric acid buffer. Comparative example 1 discloses a composition comprising SEQ ID NO:3 and histidine (no PVP/PVA). Comparative example 2 discloses a composition comprising SEQ ID NO:3, nicotinamide, and histidine (no PVP/PVA). Comparative example 3 discloses a composition comprising SEQ ID NO:3, boric acid, and glycerin (no PVP/PVA). Comparative example 4 discloses a composition comprising SEQ ID NO:3, boric acid, and sorbitol (no PVP/PVA). Comparative example 5 discloses a composition comprising SEQ ID NO:3, nicotinamide, histidine and sorbitol (no PVP/PVA). Examples 16-17 assessed stability and turbidity of the formulations (Table at pp 18-19 and 20-21). Formulation 6 had improved stability (p. 21). Example 18 assessed dry eye syndrome in a mouse model. Formulations 1-15 [limited to SEQ ID NO:3] were assessed in Ex 18 (p 22-23).
Thus, the examples are limited to formulations/compositions comprising SEQ ID NO:3 (29mer peptide).
Examiner refers applicant to the separate 112(b) rejection set forth herein which indicates ambiguities in the term “PEDF-derived”.
The specification does not provide ample written description for the compounds since the claims do not describe a single structural feature. The specification does not clearly define or provide examples of what qualify as “PEDF-derived short peptides” of the claimed invention.
As stated earlier, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. As noted above, the PDSP peptides are 5-40 amino acids in length. The term “PEDF-derived” is not expressly defined.
The possible structural variations are limitless to any class of peptide that can form peptide bonds, and make up the class of PEDF peptide. It must not be forgotten that the MPEP states that if a peptide is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. Here, though the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond compounds disclosed in the examples in the specification. Moreover, the specification lack sufficient variety of species to reflect this variance in the genus since the specification does not provide any examples what amino acids are required to have the function of PEDF peptide. Table 1 lists peptides with overlapping sequences. The examples are limited to formulations comprising SEQ ID NO:3 The specification does not provide any guidance as to the identity of critical amino acid positions for PEDF peptide functionality. Additionally, no peptides of 5 amino acids in length were reduced to practice. There is no guidance as to criticality of amino acid content/sequence or length.
Peptides that are construed as “PEDF-derived” may not have functionality. Yampolsky et al (Genetics, 2005, 170: 1459-1472) teach the effect of an amino acid exchange/mutation on a peptide (see for example, Table 3). Thus, the identity of amino acids are not only in amino acid sequence order but also in conformational/structural order can be critical to the overall function of the peptide.
The specification does not define what amino acids are required to have the same function as the instant PEDF-derived short peptides. The specification is limited to the fully defined peptide sequences of Table 1. OF these peptides, compositions of the instant claims are limited to SEQ ID NO:3. For example, there are varying lengths, varying amino acid compositions, and numerous distinct qualities that make up the genus. There is not sufficient amount of examples provided to encompass the numerous characteristics of the whole genus claimed.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
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 10 is 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 the treatment of muscle regeneration, tendon regeneration, arteriogenesis, alopecia, hair depigmentation, osteoarthritis, liver cirrhosis, or dry eye disease; or ameliorating skin aging with the peptides of SEQ ID NOs 1-3, 5, 6, 8, and 9 (core sequence- per Table 1), does not reasonably provide enablement for treatment of all recited diseases encompassed by muscle damage and eye disease, much less prevention of any disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed more recently in Liebel-Flarsheim Co. v. Medrad, Inc., 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
With regard to enablement of a claim drawn generally to treatment of impairment of a body organ’s functions, see In re Schmidt, 153 USPQ 640, 653.
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: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
(1) Breadth of claims. Claim 1 is directed to a composition comprising: a PEDF-derived short peptide (PDSP), a stabilizer, and a buffer, wherein the composition is in a liquid form, wherein a pH of the composition is in a range of 4-9, wherein the stabilizer is a copolymer of vinylpyrrolidone and vinyl acetate, wherein the buffer is a citric acid buffering system, a phosphate buffering system, a boric acid buffering system, a histidine buffering system, or a combination thereof. Claim 6 recites the composition according to claim 1, wherein the PDSP is selected from SEQ ID NO: 1, 2, 3, 5, 6, 8, 9, or a combination thereof, wherein a concentration of PDSP is 0.001%-5% w/v.
Claim 10 is directed to a method for the treatment and/or prevention of a disease, comprising administering to a subject in need thereof the composition according to claim 1, wherein the disease is selected from the group consisting of muscle damage, alopecia and/or hair depigmentation, osteoarthritis, skin aging, liver cirrhosis, eye disease, and a combination thereof.
The specification states: the term "PEDF-derived short peptide (PDSP)" refers to peptides derived from PEDF and having varying numbers of amino acid residues, such as peptides having 5 to 40 amino acid residues (para [0009]). Table 1 discloses specific peptides SEQ ID NOs:1-9. SEQ ID NOs 1-2, 5, 6, 5, and 9 share an overlapping core sequence (bold font). Table 1:
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The specification states at para [0043]: Preferably, the eye disease is selected from dry eye disease and symptoms related to dry eye disease (such as ocular surface damage and ocular surface inflammation caused by dry eye disease).
(2) The nature of the invention and predictability in the art: The invention is directed toward 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).
It is noted that pharmaceutical and biological art is generally unpredictable, requiring each embodiment to be individually assessed for physiological activity. Given this fact, historically the development of new drugs has been difficult and time- consuming. There is no absolute predictability, even in view of the high level of skill in the art.
(3) Direction or Guidance: That provided is very limited. Results are limited to a 29mer peptide derived from PEDF (SEQ ID NO:3). The instant claims require a peptide “derived” from PEDF that is 5-40 amino acids in length. The term “derived” is not defined. It is unclear as to the exact relationship between the claimed peptides and a PEDF protein sequence. For instance, a peptide could be a fragment with 100% identity, or only have 10% sequence similarity. Please see the separate but related written description (112a) and indefinite (112b) rejections.
The only disease/disorder assessed relates to desiccation induced corneal damage e.g., dry eye disease. The instant claim scope is much broader and encompasses all forms of muscle damage, alopecia and/or hair depigmentation, osteoarthritis, skin aging, liver cirrhosis, eye disease, and a combination thereof. The diseases further encompass blunt force trauma, cancer, genetic disorders, and infectious diseases. The specification has not provided any guidance as to how a disease can be prevented by the claimed PDSPs.
(4) State of the Prior Art: the following is a selection of articles relating to the instant claim scope of diseases. The following is not deemed to be a comprehensive listing.
Emerson et al. (Biodrugs 21:245-257 (2007)) is a review article that discusses various treatments for diabetic macular edema and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) (e.g., Table 1). Both of these diseases are the leading causes of vision loss in the industrialized world (abstract). One form of treatment is thermal laser photocoagulation (Sections 1.1 and 2.1). Photodynamic therapy with verteporfin (a photosenstitizing agent) has been shown to be useful for treating AMD (Section 1.2). Anti-vascular endothelial growth factor (VEGF)-A therapies (e.g., pegaptanib, ranibizumab, and bevacizumab) have been shown to improve vision in clinical trials ((Sections 1.3 and 2.3). Additionally, small interfering RNA (siRNA) to inhibit VEGF production and VEGF receptor production have also been implicated as potentially useful approaches (Section 1.4). Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME (Section 2.2).
Duh et al. (Am J Ophthalmol 137:668 – 674 (2004)) teach that pigment epithelium derived factor (PEDF) has been demonstrated to suppress ocular angiogenesis in several animal models (abstract). High levels of immunoreactive PEDF are present in the vitreous of individuals with or without ocular neovascularization, but PEDF levels are significantly higher in patients with active PDR compared with patients with choroidal neovascularization or non-neovascular retinal diseases (pp. 671- 672).
Fernandes et al. (ARVO annual meeting abstract, Investigative Ophthalmology & Visual Science 56:335 (June 2015)) teach that corneal epithelium derived PEDF is reduced in a murine model of dry eye disease (DED) suggesting its potential immunoregulatory role in the homeostasis of the ocular surface.
Hereditary optic neuropathy’s result from genetic defects that cause of vision loss and occasionally cardiac or neurologic abnormalities. There is no effective treatment (Hereditary Optic Neuropathies, Merck Manuals, accessed 3/27/2017 at URL merckmanuals.com/professional/eye-disorders/optic-nerve-disorders/hereditary-optic-neuropathies). Leber’s hereditary optic neuropathy is a maternally transmitted disorder involving a mitochondrial DNA (mtDNA) abnormality that affects cellular respiration. Although mitochondrial DNA throughout the body is affected, vision loss is the primary manifestation. Id. Most cases (80 to 90%) occur in males. Id. Diagnosis is mainly clinical and molecular genetic testing can confirm mutations responsible for the disorder. Id. There is no effective treatment for the hereditary optic neuropathy. Id. Low-vision aids (e.g., magnifiers, large-print devices, talking watches) may be helpful. Id.
Wilkinson (Biochemical Society Transactions 49:1013–1026 (2021)) teaches that Serpins (serineproteinase inhibitors) are an ancient superfamily of structurally similar proteins, the majority of which use an elegant suicide inhibition mechanism to target serine proteinases (abstract). SerpinF1 is perhaps better known as pigment epithelium-derived factor (PEDF). Devoid of inhibitory activity, this serpin has anti-angiogenic, neurotrophic and differentiation-inducing properties (p. 1018). SerpinF1 has been reported to be increased in OA cartilage [45], and a recent study demonstrated that SerpinF1 deficiency reduces cartilage damage in an age-dependent manner in the murine monoiodoacetamide OA model, and overexpression in chondrocytes enhances cytokine-induced expression of catabolic MMPs. Id.
The instant claims further encompass blunt force trauma to the eye.
Tsao et al (U.S. 9884012) teach that PEDF peptides of SEQ ID NOs: 1-3, 5, 6, 8, and 9 can be administered to promote muscle regeneration, tendon regeneration, or arteriogenesis in a subject suffering from muscle tissue damage. SEQ ID NO:3 has 100% identity with instant SEQ ID NO:3.
Tsao et al (U.S. 9938328) teach that PEDF peptides of SEQ ID NOs: 1-3, 5, 6, 8, and 9 can be administered to treat alopecia or hair depigmentation in a subject. SEQ ID NO:3 has 100% identity with instant SEQ ID NO:3.
Tsao et al (U.S. 9815878) teach that PEDF peptides of SEQ ID NOs: 1-3, 5, 6, 8, and 9 can be administered for ameliorating skin aging in a subject. SEQ ID NO:3 has 100% identity with instant SEQ ID NO:3.
Tsao et al (U.S. 9777048) teach that PEDF peptides of SEQ ID NOs: 1-3, 5, 6, 8, and 9 can be administered for treating osteoarthritis in a subject. SEQ ID NO:3 has 100% identity with instant SEQ ID NO:3.
Shih et al (U.S. 8507446) teach that PEDF peptides of SEQ ID NOs: 1-3, 5, 6, 8, and 9 can be administered for treating liver cirrhosis in a subject. SEQ ID NO:3 has 100% identity with instant SEQ ID NO:3.
Lee et al (U.S. 11760784) teach that that PEDF peptide fragment consisting of the sequence of S-X-X-A-X-Q/H-X-X-X-X I/V-I-X-R (SEQ ID NO:1) wherein each X is independently any naturally-occurring amino acid can be administered for treating dry eye disease in a subject.
(5) Working Examples: Examples 1-8 teach compositions comprising SEQ ID NO:3, PVPV A64, and histidine buffer. Examples 11-15 teach compositions comprising SEQ ID NO:3, PVPV A64, and citric acid buffer. Comparative example 1 discloses a composition comprising SEQ ID NO:3 and histidine (no PVP/PVA). Comparative example 2 discloses a composition comprising SEQ ID NO:3, nicotinamide, and histidine (no PVP/PVA). Comparative example 3 discloses a composition comprising SEQ ID NO:3, boric acid, and glycerin (no PVP/PVA). Comparative example 4 discloses a composition comprising SEQ ID NO:3, boric acid, and sorbitol (no PVP/PVA). Comparative example 5 discloses a composition comprising SEQ ID NO:3, nicotinamide, histidine and sorbitol (no PVP/PVA).
Examples 16-17 assessed stability and turbidity of the formulations (Table at pp 18-19 and 20-21). Formulation 6 had improved stability (p. 21). Example 18 assessed dry eye syndrome in a mouse model. Formulations 1-15 [limited to SEQ ID NO:3] were assessed in Ex 18 (p 22-23).
No diseases/disorders other than dry eye syndrome were assessed. No examples of preventing any disease/disorder was set forth.
(6) Skill of those in the art:
MPEP 2141.03 states (in part)" A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. V. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. At 1396, 82 USPQ2d at 1396. The "hypothetical person having ordinary skill in the art' to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art." Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner's definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
(7) The quantity of experimentation needed: given the fact that, historically, the development of new drugs has been difficult and time consuming, and especially in view of factors 1-6, the quantity of experimentation needed is expected to be substantial and undue.
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.
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 1-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (U.S. 2019/0248859; issued as Pat No 11760784, ODP rejection), and further in view of Popov et al (U.S. 20150125539).
Lee et al teach pharmaceutical compositions for treating an ophthalmic disease in a subject includes a peptide and a pharmaceutically acceptable excipient, wherein the peptide contains the sequence of SEQ ID NO: 1: S-X-X-A-X-Q/H-X-X-X-X-I/V-I-X-R, wherein each X is independently any amino acid (abstract, claim 1) . Peptides include SEQ ID NO:4 which has 100% identity with instant SEQ ID NO:3 (eg paras [0049], [0054], [0060]). Lee et al teach that the pharmaceutical compositions can be used to treat dry eye disease (e.g., paras [0008]-[0011], [0066]-[0088]; claims 7, 11, and 13). Lee teach that the composition is in the form of a solution [reads on liquid form].
Lee et al do not expressly teach that composition comprises a copolymer of vinylpyrrolidone and vinyl acetate, buffer, or pH.
Popov et al teach particles, compositions, and methods that aid transport of therapeutic agents across mucosal membrane (e.g., eyes) for ophthalmic applications (abstract, para [0003], [0090], [0241]-[0243], [0246]). The particles can include suitable polymers [stabilizers] such as poly(vinyl acetate) and polyvinylpyrrolidone, and co-polymers thereof (paras [0161], [0186]-[0204], [0213]). Popov et al further teach buffers such as citric acid and phosphate (e.g., paras [0011], [0133]-[00135], [0168]-[0169], [0249], [0324]-[0326], [0491]). Popov teach that the pH of the composition can be physiological pH (paras [0218], [0301]). The composition can be in the form of a solution, eg eye drops (paras [0252], [0266], [0312]). The compositions can be used to treat dry eye syndrome (eg paras [0333]-[0337]).
It would have been obvious to one of ordinary skill in the art to incorporate a peptide of Lee et al into the ophthalmic particles of Popov et al. Popov taught that the particles could be used to deliver therapeutic agents across mucosal membranes, including the eye (abstract, para [0003], [0090], [0241]-[0243], [0246]). Popov further taught copolymers of polyvinyl acetate and vinylpyrrolidone, buffer (citric acid or phosphate), and pH (physiological). The skilled artisan would have had a reasonable expectation of success because Popov taught methods of preparing the compositions, as well as successful administration to the eye. Popov taught that the composition can be in the form of a liquid, e.g. eyedrops. Accordingly, instant claim 1 is rendered obvious.
Regarding claims 2 and 3, the compositions can include tonicity agents [reads on osmolarity regulator] such as glycerin, lactose, mannitol, dextrose, sodium chloride, sodium sulfate, or sorbitol (e.g., Popov at paras [0282]-[0285]). Popov further teach concentrations of the tonicity agent. Id. Example 11 teaches 0.1-1% sodium chloride.
Regarding claim 4, the compositions can include an antimicrobial agent [reads on bacteriostatic], including parabens and benzalkonium chloride (BAC) (e.g., Popov at paras [0279]-[0281]). Popov further teach concentrations of the antimicrobial agent. Id. Example 11 teaches 0.001-0.05% BAC. Regarding claim 5, Popov teach that the pH of the composition can be physiological pH (paras [0218], [0301]). The composition can be in the form of a solution, eg eye drops (paras [0252], [0266], [0312]). Lee et al teach that the composition can be in the form of a solution (e.g., paras [0008], [0062], claims 9 and 15). Regarding claim 6, SEQ ID NO:4 of Lee has 100% identity with instant SEQ ID NO:3. Regarding claim 7, Popov teaches eg 0.01-2% of a stabilizer (Example 11). Regarding claim 8, Popov teach buffers including citric acid or phosphate, including 50 mM phosphate (e.g., paras [0011], [0133]-[00135], [0168]-[0169], [0249], [0324]-[0326], [0491]).
Regarding claims 3-9, Popov taught methods for preparing mucus-penetrating particles comprising a therapeutic agent and delivery of the pharmaceutical agent to the eye (Exs 1-8, 11). Popov taught suitable polymers [stabilizers] for the particles, including poly(vinyl acetate) and polyvinylpyrrolidone, and co-polymers thereof (paras [0161], [0186]-[0204], [0213]). The optimization of known effective amounts of known active agents to be administered is considered well in the competence level of an ordinary skilled artisan and pharmaceutical science, involving merely routine skill in the art. It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients and excipients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980). It is also noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The rationale to support a conclusion that the claims would have been obvious is that all the claimed elements were taught by the cited references and one skilled in the art could have combined the elements as claimed by known methods (same components and therapeutic application, treating dry eye) with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395; Sakraida V. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson's-Black Rock, Inc. V. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969).
Regarding claim 10, the compositions can be used to treat dry eye syndrome (Popov eg at paras [0333]-[0337]); Lee at paras [0008]-[0011], [0066]-[0088]; claims 7, 11, and 13).
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 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11760784 (hereinafter referred to as “the ‘784 patent”), in view of Popov et al (U.S. 2015/0125539).
Regarding claim 1, claim 9 of the ‘784 patent recites a method treating dry eye disease, comprising administering to a subject in need thereof a composition comprising a peptide and a pharmaceutically acceptable excipient, wherein the peptide comprises the sequence of S-X-X-A-X-Q/H-X-X-X-X-I/V-I-X-R (SEQ ID NO:1), wherein each X is independently any naturally-occurring amino acid. Claim 14 the ‘784 patent recites said peptide comprises the sequence of SLGAEQRTESIIHR (SEQ ID NO:2) or SLGAEHRTESVIHR (SEQ ID NO:3). Claim 16 recites that the peptide is 29 amino acids in length. SEQ ID NO:4 has 100% identity with instant SEQ ID NO:3. Claims 7 and 12 recite that the composition is the form of a solution [reads on liquid].
The claims of the ‘784 patent do not expressly teach a composition comprising the recited copolymer, buffer, or pH.
Popov et al teach particles, compositions, and methods that aid particle transport of therapeutic agents across mucosal membrane (e.g., eyes) for ophthalmic applications (abstract, para [0003], [0090], [0241]-[0243], [0246]). The particles can include suitable polymers [stabilizers] such as poly(vinyl acetate) and polyvinylpyrrolidone, and co-polymers thereof (paras [0161], [0186]-[0204], [0213]). Popov et al further teach buffers such as citric acid and phosphate (e.g., paras [0011], [0133]-[00135], [0168]-[0169], [0249], [0324]-[0326], [0491]). Popov teach that the pH of the composition can be physiological pH (paras [0218], [0301]). The composition can be in the form of a solution, eg eye drops (paras [0252], [0266], [0312]). The compositions can be used to treat dry eye syndrome (eg paras [0333]-[0337]).
It would have been obvious to one of ordinary skill in the art to incorporate a peptide of the ‘784 patent into the ophthalmic particles of Popov et al. Popov taught that the particles could be used to deliver therapeutic agents across mucosal membranes, including the eye (abstract, para [0003], [0090], [0241]-[0243], [0246]).
Popov further taught copolymers of polyvinyl acetate and vinylpyrrolidone, buffer (citric acid or phosphate), and pH (physiological). The skilled artisan would have had a reasonable expectation of success because Popov taught methods of preparing the compositions, as well as successful administration to the eye. Popov taught that the composition can be in the form of a liquid, e.g. eyedrops. Accordingly, instant claim 1 is rendered obvious.
Regarding claims 2 and 3, the compositions can include tonicity agents [reads on osmolarity regulator] such as glycerin, lactose, mannitol, dextrose, sodium chloride, sodium sulfate, or sorbitol (e.g., Popov at paras [0282]-[0285]). Popov further teach concentrations of the tonicity agent. Id. Example 11 teaches 0.1-1% sodium chloride.
Regarding claim 4, the compositions can include an antimicrobial agent [reads on bacteriostatic], including parabens and benzalkonium chloride (BAC) (e.g., Popov at paras [0279]-[0281]). Popov further teach concentrations of the antimicrobial agent. Id. Example 11 teaches 0.001-0.05% BAC.
Regarding claim 5, Popov teach that the pH of the composition can be physiological pH (paras [0218], [0301]). The composition can be in the form of a solution, eg eye drops (paras [0252], [0266], [0312]). Lee et al teach that the composition can be in the form of a solution (e.g., paras [0008], [0062], claims 9 and 15).
Regarding claim 6, claim 9 of the ‘784 patent method treating dry eye disease, comprising administering to a subject in need thereof a composition comprising a peptide and a pharmaceutically acceptable excipient, wherein the peptide comprises the sequence of S-X-X-A-X-Q/H-X-X-X-X-I/V-I-X-R (SEQ ID NO:1), wherein each X is independently any naturally-occurring amino acid. Claim 14 the ‘784 patent recites said peptide comprises the sequence of SLGAEQRTESIIHR (SEQ ID NO:2) or SLGAEHRTESVIHR (SEQ ID NO:3). Claim 16 recites that the peptide is 29 amino acids in length. SEQ ID NO:4 has 100% identity with instant SEQ ID NO:3.
Regarding claim 7, Popov teaches eg 0.01-2% of a stabilizer (Example 11).
Regarding claim 8, Popov teach buffers including citric acid or phosphate, including 50 mM phosphate (e.g., paras [0011], [0133]-[00135], [0168]-[0169], [0249], [0324]-[0326], [0491]).
Regarding claims 3-9, Popov taught methods for preparing mucus-penetrating particles comprising a therapeutic agent and delivery of the pharmaceutical agent to the eye (Exs 1-8, 11). Popov taught suitable polymers [stabilizers] for the particles, including poly(vinyl acetate) and polyvinylpyrrolidone, and co-polymers thereof (paras [0161], [0186]-[0204], [0213]). The optimization of known effective amounts of known active agents to be administered is considered well in the competence level of an ordinary skilled artisan and pharmaceutical science, involving merely routine skill in the art. It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients and excipients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980). It is also noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The rationale to support a conclusion that the claims would have been obvious is that all the claimed elements were taught by the cited references and one skilled in the art could have combined the elements as claimed by known methods (same components and therapeutic application, treating dry eye) with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395; Sakraida V. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson's-Black Rock, Inc. V. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969).
Regarding claim 10, claims 1 and 9 of the ‘784 patent recite that the peptide is useful in a method of treating dry disease.
Conclusion
No claims are allowed.
Claims 1-10 are pending and are rejected.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654
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