DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
The claim listing filed 31 August 2023 is pending. Claims 1-10 are being examined on the merits in this office action.
Priority
The present application claims status as a 371 (National Stage) of PCT/KR2022/005662 filed 20 April, 2022, and claims priority under 119(a)-(d) to Korean Patent Application No. 10-2021-0050985 filed 20 April 2021.
Receipt is acknowledged of certified copies of papers submitted under 35 USC 119(a)-(d) for Korean Application No. 10-2021-0050985, which papers have been placed of record in the file. Please note that the application is in Korean and thus cannot be verified.
Please note that Applicants cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 31 August 2023 and 6 August 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statements are being considered by the examiner.
Claim Objections
Claim 5 is objected to because of the following informalities: The typographical error “NLRP3 inflmmasome” in the preamble. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1 and 2 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claim(s) recite(s) to “a peptide comprising any one amino acid sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 7.”. SEQ ID NOs: 1, 4, 6, and 7 are found in nature. The peptide segments detailed in the instant invention are not markedly different form the naturally occurring peptide. This judicial exception is not integrated into a practical application because the claim recites a product of nature “a peptide” and no additional limitation. Claim 2 does not include additional elements that are sufficient to amount to significantly more than the judicial exception because while claim 2 recites a function of the peptide, the peptide already had that function. For example, Touro College of Pharmacy (Touro College, Ozempic and Wegovy: What you need to know 2024) states Semaglutide was first developed to treat type 2 diabetes and managing bloods sugar levels, and then was approved for chronic weight management. Regardless of the initial use, Semaglutide always had the ability to manage weight (pg. 1 “Semaglutide, the active ingredient in Ozempic and Wegovy, was originally approved to treat type 2 diabetes mellitus as Ozempic, and later approved for treatment of obesity as Wegovy.”). “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. See MPEP §2112.01.
Note: SEQ ID NO: 2, 3, and 5 are excluded from this rejection because those specific SEQ ID NOs were not found in the prior art.
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)(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, 5-8, and 10 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Pal et al., hereafter “Pal” (“Inhibition of NLRP3 inflammasome activation by cell-permeable stapled peptides.” Sci Rep 9, 4913 (2019). https://doi.org/10.1038/s41598-019-41211-3.).
Regarding claim 1, Pal teaches a peptide comprising the instant SEQ ID NO: 1 (pg. 3, “Considering these factors, we chose residues 16–30 from helix 2 as our peptide template 16TAEELKKFKLKLLSV30 (Fig. 1B and Table 1).”).
Regarding claim 2, Pal teaches a peptide comprising the instant SEQ ID NO: 1 inhibiting NLRP3 inflammasome activation, showing that the peptides have the effect of suppressing the overexpression of IL-1β and IL-18, which induces inflammasome chronic inflammatory diseases, such as type 2 diabetes and obesity, through NLRP3 inflammasome signaling inhibition ([Abstract] “Interleukin-1β (IL-1β) is a major cytokine that initiates and enhances inflammatory responses. Excessive IL-1β production is a characteristic of most chronic inflammatory diseases, including atherosclerosis, type 2 diabetes, and obesity, which affect a large proportion of the global population. … The peptides were effectively internalized by human monocytic cells and efficiently suppressed the release of the inflammasome-regulated cytokines IL-1β and IL-18, following exogenous activation of the NLRP3 inflammasome. The peptides reduced ASC speck formation and caspase-1 processing thereby suppressing pro-IL-1β processing and release of active IL-1β. ”; pg. 2, “The resulting peptides were stable, could effectively enter cells and reduced inflammasome-mediated release of IL-1 cytokines from human monocytes in response to NLRP3 inflammasome activation. … Our study is the first to report peptide-based modulators as an effective alternative to small molecule inhibitors for disrupting immune-cell function in NLRP3-mediated inflammatory pathways. As the modular organization of NLRP3 and ASC is shared among several other proteins, our findings may serve as a framework for designing peptides that target other innate immune receptors.”).
Regarding claim 5, Pal teaches that the peptide-based modulators are an effective alternative for inhibitors disrupting immune cell function in in NLRP3-mediated pathways. (pg. 2, “Our study is the first to report peptide-based modulators as an effective alternative to small molecule inhibitors for disrupting immune-cell function in NLRP3-mediated inflammatory pathways. As the modular organization of NLRP3 and ASC is shared among several other proteins, our findings may serve as a framework for designing peptides that target other innate immune receptors.”).
One of ordinary skill in the art would take this teaching and come to the conclusion that the peptide disclosed by Pal is capable of inhibiting NLRP3 inflammasome activity, as Pal teaches that the peptide-based modulator is an effective alternative to a small molecule that inhibits NLRP3 pathways.
Regarding claim 6, Pal teaches excessive IL-1β production as being a characteristic of type 2 diabetes, a metabolic disease ([Abstract] “Excessive IL-1β production is a characteristic of most chronic inflammatory diseases, including atherosclerosis, type 2 diabetes, and obesity, which affect a large proportion of the global population.”).
Regarding claim 7, Pal teaches excessive IL-1β production as being a characteristic of obesity and type 2 diabetes mellitus, as required by the limitation set forth in claim 7 ([Abstract] “Excessive IL-1β production is a characteristic of most chronic inflammatory diseases, including atherosclerosis, type 2 diabetes, and obesity, which affect a large proportion of the global population.”).
Regarding claim 8, Pal teaches that NLRP3 inflammasome activity has been linked chronic inflammation in gout (pg. 2; “The NLRP3 inflammasome has also been linked to chronic inflammation in conditions such as gout , pulmonary inflammation, atherosclerosis and type 2 diabetes.”).
Claims 1, 2, 4 and 10 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Reed et al, hereafter, “Reed” (US 6953691 B2).
Regarding claim 1, Reed discloses a peptide that comprises the amino acid sequences EELKKFKLKLLSV (SEQ ID NO: 1) and DALDLTDKLVS (SEQ ID NO: 7), and additionally a peptide that comprises the amino acid sequence DVDLKKFKMHLED (SEQ ID NO: 4). See the peptides represented by SEQ ID NO: 8 (comprises instant SEQ ID NO: 4) SEQ ID NO: 9 (comprises instant SEQ ID NOs: 1 and 7); (col. 14 lines. 20-23; “Preferably, PAAD domain-containing functional fragments comprise 15 or more contiguous amino acids selected from the group consisting of SEQ ID NOS:1-14.”).
Regarding claim 2, with regard to the limitation of “downregulating interleukin 1β (IL-1β) and interleukin 18 (IL-18) by inhibiting NLRP3 inflammasome signaling”, the peptides of Reed comprise the amino acid sequences that are claimed to downregulate IL-1β and IL-18 and because a chemical composition and its properties are inseparable, a person of ordinary skill in the art would reasonably expect the peptide of Reed to also downregulate IL-1β and IL-18. MPEP 2112.01 (II).
Regarding claim 4, with regard to the limitation "a composition comprising the peptide according to claim 1”, Reed teaches that the present invention provides composition containing an isolated, purified PAAD domain containing mature protein (col. 15 lines. 45-47; “The present invention also provides compositions containing an acceptable carrier and any of an isolated, purified PAAD domain-containing mature protein…”).
Regarding claim 10, with regard to the limitation “the composition according to claim 4, which is a pharmaceutical composition”, Reed teaches the methods of administering the polypeptide can be in the form of a pharmaceutical composition (col. 16, lines. 15-17; “Methods of administering therapeutic polypeptides are well known to those skilled in the art, for example, in the form or a pharmaceutical composition.”).
Claims 1, 2, 4, and 10 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Vertino (US 6911306 B1).
Regarding claim 1, Vertino discloses a peptide that comprises the amino acid sequence MGRARDAILD (SEQ ID NO: 6). See the peptide represented by SEQ ID NO: 6; (col. 10, lines. 35-38; “The TMS1 N-terminal polypeptide may comprise an amino acid sequence selected from the group consisting of SEQ ID NO:6…”).
Regarding claim 2, with regard to the limitation of “downregulating interleukin 1β (IL-1β) and interleukin 18 (IL-18) by inhibiting NLRP3 inflammasome signaling”, the peptides of Reed comprise the amino acid sequences that are claimed to downregulate IL-1β and IL-18 and because a chemical composition and its properties are inseparable, a person of ordinary skill in the art would reasonably expect the peptide of Reed to also downregulate IL-1β and IL-18. MPEP 2112.01 (II).
Regarding claim 4, with regard to the limitation "a composition comprising the peptide according to claim 1”, Vertino teaches that the present invention provides composition containing an isolated, purified PAAD domain containing mature protein (col. 15 lines. 45-47; “The present invention also provides compositions containing an acceptable carrier and any of an isolated, purified PAAD domain-containing mature protein…”).
Regarding claim 10, with regard to the limitation “the composition according to claim 4, which is a pharmaceutical composition”, Vertino teaches the invention being made into a pharmaceutical composition (col. 54, lines. 58-60; “The invention further embraces pharmaceutical preparations or compositions useful for treating subjects having or at risk of having the disorders described herein.”).
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.
Claim 3, 4 and 10 is rejected under 35 U.S.C. 103 as being unpatentable over Reed et al, hereafter, “Reed” (US 6953691 B2), as applied to claim 1 above, and in further view of Takeshima et al., hereafter “Takeshima” (“Translocation of analogues of the antimicrobial peptides magainin and buforin across human cell membranes.” J Biol Chem. 2003 Jan 10;278(2):1310-5. doi: 10.1074/jbc.M208762200. Epub 2002 Nov 1. PMID: 12417587."), cited in the IDS filed 31 August 2023.
Claim 3 is drawn to a fusion peptide in which the peptide according to claim 1 and a cell-penetrating peptide (CPP) are conjugated.
Reed teaches a peptide that comprises the amino acid sequences EELKKFKLKLLSV (SEQ ID NO: 1) and DALDLTDKLVS (SEQ ID NO: 7), and additionally a peptide that comprises the amino acid sequence DVDLKKFKMHLED (SEQ ID NO: 4). See the peptides represented by SEQ ID NO: 8 (comprises instant SEQ ID NO: 4) SEQ ID NO: 9 (comprises instant SEQ ID NOs: 1 and 7); (col. 14 lines. 20-23; “Preferably, PAAD domain-containing functional fragments comprise 15 or more contiguous amino acids selected from the group consisting of SEQ ID NOS: 1-14.”).
Reed does not teach a fusion peptide comprising the peptide of claim 1 and a cell-penetrating peptide.
Takeshima teaches a peptide comprising the TAT peptide (YGRKKRRQRRR) that is able to penetrate cells (pg. 1310; “In this study, we investigated the translocation of fluorescent-labeled analogues of magainin 2 and buforin 2 across human cell membranes in comparison with the Tat-(47–57) peptide (Table I), a representative Arg-rich cell-penetrating peptide.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Reed's taught peptide by combining it with the TAT peptide taught by Takeshima in order to facilitate intracellular administration of the peptide claimed in the instant invention. This modification of the art takes a known peptide and a known method of penetrating a cell, and combines the two techniques.
One would have had a reasonable expectation of success because the well-established function of TAT as a cell penetrating peptide is used in the art to facilitate intracellular transport of cells under KSR rationale D. (See MPEP 2143 (l)(D)).
Regarding claim 4, with regard to the limitation "a composition comprising the peptide according to claim 1 or a fusion peptide comprising the peptide and a cell-penetrating peptide (CPP) conjugated thereto”, the combined teachings of Reed and Takeshima as applied above read on this limitation.
Regarding claim 10, with regard to the limitation “the composition according to claim 4, which is a pharmaceutical composition”, Reed teaches the methods of administering the polypeptide can be in the form of a pharmaceutical composition (col. 16, lines. 15-17; “Methods of administering therapeutic polypeptides are well known to those skilled in the art, for example, in the form or a pharmaceutical composition.”).
Claims 3, 4 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Vertino (US 6911306 B1) as applied to claim 1 above, and in further view of Takeshima et al., hereafter “Takeshima” (“Translocation of analogues of the antimicrobial peptides magainin and buforin across human cell membranes.” J Biol Chem. 2003 Jan 10;278(2):1310-5. doi: 10.1074/jbc.M208762200. Epub 2002 Nov 1. PMID: 12417587.").
Claim 3 is drawn to a fusion peptide in which the peptide according to claim 1 and a cell-penetrating peptide (CPP) are conjugated.
Vertino teaches a peptide that comprises the amino acid sequence MGRARDAILD (SEQ ID NO: 6). See the peptide represented by SEQ ID NO: 6; (col. 10, lines. 35-38; “The TMS1 N-terminal polypeptide may comprise an amino acid sequence selected from the group consisting of SEQ ID NO:6…”).
Vertino does not teach a fusion peptide comprising the peptide of claim 1 and a cell-penetrating peptide.
Takeshima teaches a peptide comprising the TAT peptide (YGRKKRRQRRR) that is able to penetrate cells (pg. 1310; “In this study, we investigated the translocation of fluorescent-labeled analogues of magainin 2 and buforin 2 across human cell membranes in comparison with the Tat-(47–57) peptide (Table I), a representative Arg-rich cell-penetrating peptide.”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Vertino’s taught peptide by combining it with the TAT peptide taught by Takeshima in order to facilitate intracellular administration of the peptide claimed in the instant invention. This modification of the art takes a known peptide and a known method of penetrating a cell, and combines the two techniques.
One would have had a reasonable expectation of success because the well-established function of TAT as a cell penetrating peptide is used in the art to facilitate intracellular transport of cells under KSR rationale D. (See MPEP 2143 (l)(D)).
Regarding claim 4, with regard to the limitation "a composition comprising the peptide according to claim 1 or a fusion peptide comprising the peptide and a cell-penetrating peptide (CPP) conjugated thereto”, the combined teachings of Vertino’s peptide and Takeshima’s TAT peptide as applied above read on this limitation.
Regarding claim 10, with regard to the limitation “the composition according to claim 4, which is a pharmaceutical composition”, Vertino teaches the invention being made into a pharmaceutical composition (col. 54, lines. 58-60; “The invention further embraces pharmaceutical preparations or compositions useful for treating subjects having or at risk of having the disorders described herein.”).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Pal et al., hereafter “Pal” (“Inhibition of NLRP3 inflammasome activation by cell-permeable stapled peptides.” Sci Rep 9, 4913 (2019). https://doi.org/10.1038/s41598-019-41211-3.), as applied to claim 6 above, and in further view of Van Gorp et al., hereafter “Van Gorp”, (“Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation”, Proc. Natl. Acad. Sci. U.S.A. 113 (50) 14384-14389, https://doi.org/10.1073/pnas.1613156113 (2016)).
Claim 9 is drawn to “The method according to claim 6, wherein the autoinflammatory disease is Muckle-Wells syndrome (MWS), latent autoimmune diabetes in adults (LADA), familial cold autoinflammatory syndrome (FCAS), cryopyrin-associated periodic syndrome (CAPS), neonatal-onset multisystem inflammatory disease (NOMID), chronic infantile neurologic cutaneous and articular (CINCA) syndrome, familial Mediterranean fever (FMF), systemic juvenile idiopathic arthritis (SJIA), systemic juvenile idiopathic rheumatoid arthritis, or rheumatoid arthritis.”.
The teachings of Pal, as applied to claim 6, are described and applied above.
Pal does not teach the autoinflammatory disease being Muckle-Wells syndrome (MWS), latent autoimmune diabetes in adults (LADA), familial cold autoinflammatory syndrome (FCAS), cryopyrin-associated periodic syndrome (CAPS), neonatal-onset multisystem inflammatory disease (NOMID), chronic infantile neurologic cutaneous and articular (CINCA) syndrome, familial Mediterranean fever (FMF), systemic juvenile idiopathic arthritis (SJIA), systemic juvenile idiopathic rheumatoid arthritis, or rheumatoid arthritis.
Van Gorp teaches that mutation in inflammasomes causes autoinflammatory diseases, including but not limited to cryopyrin-associated periodic syndrome (CAPS) and familial Mediterranean fever (FMF) (pg. 1;“ Inflammasomes are multiprotein complexes that culminate in processing of caspase-1, thereby promoting maturation of proIL-1β and proIL-18 into their active forms. … Conversely, mutations in genes coding for inflammasome components and regulators cause debilitating systemic autoinflammatory diseases, of which cryopyrin-associated periodic syndromes (CAPS; NLRP3 mutations), autoinflammation with infantile enterocolitis (AIFEC; NLRC4 mutations), hyperimmunoglobulinemia syndrome (HIDS; MVK mutations) and familial Mediterranean fever (FMF; MEFV mutations) are notable examples.”).
It would have been obvious before the effective filing date of the claimed invention for one of ordinary skill in the art to have combined the teachings of Pal, as applied to claim 6, in view of Van Gorp to have arrived at the claimed invention. Pal teaches a peptide-based modulator that is an effective alternative to a small molecule that inhibits NLRP3 pathways. Van Gorp teaches that CAPS and FMF are autoinflammatory diseases that can be caused by mutations in genes coding for inflammasome components, specifically CAPS being associated with NLRP3 mutations. It would have been obvious to the ordinary artisan to combine the teachings of Pal and Van Gorp because Pal teaches that the peptide-based modulator is an effective alternative to inhibit NLRP3 pathways.
Therefore, it would have been prima facie obvious to the artisan of ordinary skill in the art at the time before the effective filling date of the claimed invention.
Allowable Subject Matter
The following is a statement of reasons for the indication of allowable subject matter: SEQ ID NOs: 2, 3, and 5, as recited in claim 1, were not taught in the art with 100% sequence identity. The closest sequence match to the instant SEQ ID NO: 2 is a segment of the nucleotide sequence described in Brown et al. (“Unusual biology across a group comprising more than 15% of domain Bacteria.” Nature 523, 208–211 (2015). https://doi.org/10.1038/nature14486) with 81% sequence similarity, as seen below. The closest sequence match to the instant SEQ ID NO: 3 is a segment of the nucleotide sequence disclosed in Mintz et al. (US 7745391 B2) with 74.6% sequence similarity to SEQ ID NO: 1029122, as seen below. The closest sequence match to the instant SEQ ID NO: 5 is a segment of the nucleotide sequence described in Wu et al. (US 9029636 B2) with 70.1% sequence similarity to SEQ ID NO: 159528, as seen below.
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Summary
Claim 5 is objected to. Claims 2-10 are rejected under 35 U.S.C. 112(b). Claims 1 and 2 are rejected under 35 U.S.C. 101. Claims 1, 2, 4-8, and 10 are rejected under 35 U.S.C. 102(a)(2). Claims 3, 4, and 9-10 is rejected under 35 U.S.C. 103.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Daliyah M. Brown whose telephone number is (571)272-0136. The examiner can normally be reached Monday-Thursday 9:00 am - 4:30 pm.
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/Daliyah M. Brown/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654