DETAILED ACTION
Examiner acknowledges receipt of the reply filed 6/30/2026, in response to the non-final office action mailed 4/02/2026.
Claims 14, 53-55, 57, and 59-64 are pending. Claims 56 and 58 have been cancelled. Claims 59 and 60 remain withdrawn from further consideration for the reasons made of record.
Claims 14, 53-55, 57, and 61-64 are being examined on the merits in this office action. In reply to this office action, the status of claims 59 and 60 should be corrected to reflect their withdrawn status.
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 .
Examiner Comment
Upon further consideration, a second non-final office is warranted. The instant action is a second non-final.
Oath/Declaration
The Chen Declaration filed 6/30/2026 is acknowledged. The declaration establishes common ownership of cited reference Rom et al (U.S. 2021/0315963) under 35 USC §102(b)(2)(A).
Specification- withdrawn in part
The objection to the specification, with regard to the embedded hyperlink, is withdrawn in view of the amendment filed 6/30/2026.
Claim Objections- withdrawn
The objection of claims 14, 61, and 63 is withdrawn in view of the amendment filed 6/30/2026.
Claim Rejections - 35 USC § 112- withdrawn
The rejection of claims 14, 53-55, 57, 58, and 62-64 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in view of the amendment filed 6/30/2026.
Claim Rejections - 35 USC § 102- withdrawn
The rejection of claims 14, 53-55, 57, 58, and 62-64 under 35 U.S.C. 102(a)(2) as being anticipated by Rom et al (U.S. 2021/0315963; PGPUB of copending Appl. No 17/266897 (“the ‘897 application”- ODP rejection); parent of Appl No 18/163773- cited in ODP rejection), is withdrawn in view of the Chen declaration filed 6/30/2026 establishing common ownership of the Rom reference under 35 USC §102(b)(2)(A), thereby removing the reference as prior art.
Claim Rejections - 35 USC § 103- withdrawn
The rejection of claims 14, 53-55, 57, 58, and 61-64 under 35 U.S.C. 103 as being unpatentable over Rom et al (U.S. 2021/0315963), as applied to claims 14, 53-55, 57, 58, and 62-64 above, and further in view of Zhang et al (Current Medicinal Chemistry 19:1602-1618 (2012)) and Resh (Prog Lipid Res. 63:120–131 (2016)), is withdrawn in view of the Chen declaration filed 6/30/2026 establishing common ownership of the Rom reference under 35 USC 102(b)(2)(a).
The rejection of claims 14, 53-55, 57, 58, and 61-64 under 35 U.S.C. 103 as being unpatentable over Chen (WO2012109561 cited in IDS filed 7/09/2025) in view of Patel (Curr Diabetes Rev 2014;10(4):238-50), Bhatt (HepatoBiliary Surg Nutr 4(2):101-108 (2015)), Zhang et al (Current Medicinal Chemistry 19:1602-1618 (2012)) and Resh (Prog Lipid Res. 63:120-131 (2016)), is withdrawn following further consideration of the claims. A new 103 rejection further citing two new references is set forth herein.
Response to Arguments
Applicant’s amendment and declaration with respect to the withdrawn objections and rejections have been fully considered and are persuasive. The rejections have been withdrawn.
Applicant's arguments filed 6/30/2026 with respect to the maintained rejections have been fully considered but they are not persuasive.
Upon further consideration, a new ground(s) of rejection is made in view of the amendment filed 6/30/2026.
An action on the merits is set forth herein.
New Objection/Rejections
Claim Objections- New
Claim 61 is objected to because of the following informalities:
Claim 61 should be amended to recite “or a pharmaceutically acceptable salt thereof .
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 57 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. This is a new rejection necessitated by the amendment filed 6/30/2026.
Claim 57 depends from claim 14. Instant claim 14 recites “amino acid product to the subject in need thereof, wherein the N-acyl amino acid product has a fatty acid component and an amino acid component, wherein the amino acid component is glycine-glycine-leucine or glycine-glycine-D-leucine”.
Claim 57 recites “The method of claim 14 wherein the amino acid component is a peptide”. Claim 57 is deemed to not further limit claim 14 because claim 57 merely recites the term “peptide”, of which claim 14 recites 2 peptides; GGL and GGdL.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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) 14, 53-55, 57, and 61-64 are rejected under 35 U.S.C. 103 as being unpatentable over Chen (WO2012109561- previously cited) in view of Patel (Curr Diabetes Rev 2014;10(4):238-50- previously cited), Bhatt (HepatoBiliary Surg Nutr 4(2):101-108 (2015)- previously cited), Armstrong (Lancet 387:679-690 ((2016)), Zhang et al (Current Medicinal Chemistry 19:1602-1618 (2012)- previously cited), Resh (Prog Lipid Res. 63:120–131 (2016)- previously cited), and Burnstein (Mol Pharmacol 93:228-238 (2017)). This is a new rejection.
Chen teaches a method of treating obesity and metabolic syndrome in subjects comprising administering GGL (also referred to as diapin, see e.g., Example 2, abstract, claims 1-2). Chen teaches using animal models of obesity and diabetes (ob/ob and db/db). Chen specifically teaches that diapin stimulated GLP-1 secretion, insulin secretion and lowers blood glucose levels (see e.g. Figures 7-10). Chen teaches “The amount of the composition administered is therapeutically effective to achieve at least one of the following: reducing blood glucose levels, stimulating insulin secretion, stimulating GLP-1 secretion, reducing insulin resistance, and improving glycemic control” (e.g. para. [0066]).
Chen does not reduce to practice treating a subject with steatohepatitis.
Patel teaches that GLP-1 secretion promotes insulin production, glucose utilization and decreases triglycerides (see abstract). Furthermore, reduction in insulin resistance, glucose levels and improved glucose utilization will lower serum triglycerides.
Bhatt teaches that insulin resistance appears to be a critical contributing factor to NAFLD (e.g., p. 103). Bhatt teaches “Elevated circulating free fatty acid levels, in part related to diminished suppression of adipose tissue lipolysis by insulin, result in increased delivery of free fatty acids to the liver. The synthesis of excess triglyceride in the liver is driven by this supply of fatty acids and the accumulation of excess liver fat is further exacerbated by impaired hepatic fatty acid oxidation secondary to insulin resistance. When glucose levels are elevated in the context of prediabetes or overt diabetes, this provides further substrate for triglyceride synthesis. Additionally, impaired very low density lipoprotein (VLDL) secretion, which commonly occurs with insulin resistance, further contributes to hepatic fat accumulation. Insulin resistance is not only a factor in obesity and diabetes, but also may be an underlying mechanism for NAFLD even in non-obese individuals without diabetes, as noted in a euglycemic insulin clamp study” (see page 103, left column). Bhatt teaches that glucose control in diabetic patients resulted in improvement in hepatic fibrosis in patients with NAFLD (see page 105, right column, second paragraph). Bhatt teaches a study showed improved steatosis and NASH histology following GLP-1 agonist treatment of overweight obese subjects with diabetes (see page 105, left column, last paragraph).
Armstrong teaches use of Liraglutide (GLP-1 agonist) in patients with NASH and with or without diabetes (see Method, Abstract OC-016). Armstrong teaches that both patients with diabetes and without diabetes and NASH achieved the primary endpoint and resolution of NASH (see page 686, right column, second paragraph).
Although Chen teaches the tripeptide GGL, the reference does not expressly teach an N-acylated GGL [claimed N-acyl amino acid product].
Zhang et al teach that lipidation is a post-translational modification of proteins that is also found its use in designing peptide drugs. The presence of a lipid group in peptides modulates their hydrophobicity, secondary structures and self-assembling propensities while retaining their abilities to bind to target receptors. Lipidation improves peptides’ metabolic stability, membrane permeability, bioavailability, and changes peptides’ pharmacokinetic and pharmacodynamic properties (abstract; pp. 1602-1609). Zhang et al disclose lipidation strategies in peptide drug design, the effects of the chain length and anchor position of fatty acids in peptide lipidation, the physicochemical and biological properties or peptides, and the synthesis strategies for peptide lipidation. Id.
Resh is a review article discussing fatty acylation of proteins. Proteins can be modified with fatty acids that range in length from eight to over twenty carbons. The predominant species acylated to proteins are saturated chain fatty acids, but monounsaturated and polyunsaturated fatty acids can also be attached (p. 121). Table 1 discloses lipids/fatty acids used in a peptide/protein fatty acylation. Lipids include but are not limited to myristate (C14), palmitate (C16), stearate (C18), and arachidonic acid (C20) (Table 1).
Burnstein teaches N-acyl amino acid conjugates and their therapeutic potential. The reference teaches that endogenous N-acyl amino acids include palmitoyl glycine (16:0), oleoyl glycine, and arachidonoyl glycine (Table 1). Of note, the most widely studied member is N-arachidonoyl glycine (NAGly) (abstract, Table 2- indicating functional activities, Fig 4, pp. 232-235). Examiner acknowledges that NAGly is a single amino acid. However, the teachings of Burnstein underscore that N-acylated glycine, particularly N-arachidonoyl glycine, was known in the prior art.
It would have been obvious before the effective filing date of the claimed invention to treat patients with steatohepatitis and obesity/diabetes/metabolic syndrome with the compositions of Chen. One of ordinary skill in the art would have been motivated to do so given that lowering glucose levels, improving glucose utilization and increasing GLP-1 secretion would be beneficial in treating patients with steatohepatitis. Chen teaches treatment of diabetes/obesity/metabolic syndrome with diapin (the peptide of the instant claims) and the peptide was capable of lowering blood sugar, improving glucose utilization, reducing insulin resistance and stimulating GLP-1 secretion all of which would be beneficial in treatment patients with steatohepatitis. Patel and Bhatt further taught the same subject population and shared/common conditions/symptoms associated with steatohepatitis, diabetes and/or obesity. Bhatt teaches that insulin resistance is a critical contributing factor to NAFLD (steatohepatitis), and that improving insulin sensitivity ameliorates hepatic steatosis and fibrosis. Bhatt explains that excess hepatic fat accumulation results from insulin resistance and impaired lipid handling. Armstrong teaches that treatment with a GLP-1 agonist liraglutide, improved NASH outcomes and achieved resolution of NASH in patients. Thus, GLP-1 pathway modulation improved insulin sensitivity and improved NAFLD/NASH. Given that Chen's GGL peptide stimulates GLP-1 secretion (i.e., the same metabolic GLP-1 pathway as taught by Armstrong) improves insulin secretion, and reduces insulin resistance, a person of ordinary skill in the art would have had a reasonable expectation of success in using GGL or GGdL to treat NASH or NAFLD in subjects with similar beneficial results.
The skilled artisan would further have understood that Zhang taught methods of improving pharmacokinetic and pharmacodynamic properties of the peptides of Chen, e,g. lipidation comprising an N-acyl group. As taught by Zhang, incorporation of a fatty acid at the N-terminus could improve metabolic stability, membrane permeability, and bioavailability. Table 1 of Resh provided a list of fatty acids that were known and used in protein acylation in the prior art. The skilled artisan would have had a reasonable expectation of success in preparing an N-acylated GGL peptide because Zhang and Resh taught methods as well as specific fatty acids, e.g., N-arachidonoyl, that could be used in a lipidation method. The skilled artisan would further have a reasonable expectation of success of incorporating N-arachidonoyl into GGL or GGdL to yield a functional therapeutic for treating steatohepatitis because Burnstein taught that N-arachidonoyl glycine (NAGly) was known. Thus, incorporating NAGly at the N-terminus of GGL or GGdL would be expected to retain functional utility of GGL or GGdL tripeptide, as taught by Chen.
Accordingly, administering an effective amount of an N-acylated GGL peptide [reads on N-acyl amino acid product] to a subject with steatohepatitis, in order to treat the steatohepatitis is rendered obvious (instant claims 14 and 57).
Regarding claims 53-55, Zhang et al and Resh taught polyunsaturated fatty acids (PUFA), as well as omega 3 fatty acids, and metabolites thereof, e.g., myristate, palmitoleate, stearate, and oleate, and the polyunsaturated fatty acids arachidonate and eicosapentanoate (e.g., Resh at Table 1, pp 8-11, Zhang at Table 1, pp. 1603-1606, 1609-1614).
Regarding claim 61, a peptide of N-arachidonoyl-Gly-Gly-Leu is rendered obvious in view of the teachings of the cited references. Chen teaches that the tripeptide GGL lowers blood sugar, improves glucose utilization, reduces insulin resistance and stimulates endogenous GLP-1 secretion. GLP-1 secretion promotes insulin production, glucose utilization and decreases triglycerides (see abstract). Furthermore, reduction in insulin resistance, glucose levels and improved glucose utilization will lower serum triglycerides (Patel). Bhatt teaches that insulin resistance is a critical contributing factor to NAFLD (steatohepatitis), and that improving insulin sensitivity ameliorates hepatic steatosis and fibrosis. Bhatt explains that excess hepatic fat accumulation results from insulin resistance and impaired lipid handling. Armstrong teaches that treatment with a GLP-1 agonist liraglutide, improved NASH outcomes and achieved resolution of NASH in patients. Thus, GLP-1 pathway modulation improved insulin sensitivity and improved NAFLD/NASH. The skilled artisan would have understood that GGL of Chen stimulates GLP-1 secretion (i.e., the same metabolic GLP-1 pathway as taught by Armstrong) improves insulin secretion, and reduces insulin resistance, a person of ordinary skill in the art would have had a reasonable expectation of success in using GGL or GGdL to treat NASH or NAFLD in subjects with similar beneficial results. Zhang et al and Resh teach lipidation (e.g., N-acyl with a fatty acid), and Resh further teaches specific fatty acids, including arachidonoyl. Burnstein further indicates that arachidonoyl at the N-terminus of glycine was known in the prior art. Thus, the skilled artisan would have had a reasonable expectation of success in preparing N- arachidonoyl-GGL (methods of Zhang and Patel) and using N- arachidonoyl-GGL to treat NASH or NAFLD in subjects with similar beneficial results.
Regarding claim 62, Bhatt teaches that steatohepatitis includes non-alcoholic steatohepatitis (NASH) (e.g., p. 101-102).
Regarding claim 63, Bhatt teaches that steatohepatitis is associated with inflammation and cell injury, as well as fatty liver, elevated triglycerides and cholesterol (p. 101-103). Patel discloses an association with atherosclerosis (abstract). Thus, the skilled artisan would have recognized that treating steatohepatitis with the claimed N-acyl amino acid product there would have been a reasonable expectation of success in also reducing the physical symptoms associated with steatohepatitis, e.g., liver fat, inflammation and injured hepatocytes, and atherosclerotic plaques.
Regarding claim 64, Bhatt teaches that patients with NASH are much more likely to progress to clinically significant cirrhosis, portal hypertension, and liver failure. When cirrhosis develops in the context of NAFLD, there also is a several-fold increased risk of hepatocellular carcinoma (p. 101). Thus, the skilled artisan would have recognized that treatment with the claimed N-acyl amino acid product would help treat/delay/mitigate development of cirrhosis and/or hepatocellular carcinoma.
Accordingly, claims 14, 53-55, 57, and 61-64 are rendered obvious in view of the teachings of the cited references.
Response to Arguments- as relating to the previous 103 rejection, withdrawn herein
Examiner notes the new 103 rejection set forth in this action further includes the Armstrong reference.
Applicant traversed the rejection at pp. 10-12 of the reply filed 6/30/2026. Applicant asserts that Chen discloses administering the unmodified tripeptide Gly-Gly-Leu and related peptides to treat prediabetes, diabetes, obesity, high blood pressure, and metabolic syndrome (p. 10). Applicant asserts that Chen discloses acetylation (2 carbon acyl group) but no disclosure of attaching a long-chain or polyunsaturated fatty acids the tripeptide (reply at p. 10). Applicant asserts that Patel and Bhatt do not cure the alleged deficiencies of Chen. Id. Applicant asserts that Zhang and Resh are review articles addressed to peptide lipidation in general, and the references do not teach N-acylation a tripeptide, or mention steatohepatitis, NAFLD, or NASH (pp. 10-11).
Applicant alleges “Examiner's rationale addresses only why a person of ordinary skill might lipidate a peptide generally to improve pharmacokinetic properties” (reply at p. 12). Applicant asserts the instant claims are directed to treating steatohepatitis, not merely a lipidated form of the Chen tripeptide. Applicant alleges that the cited references provide no reasonable expectation that such N-acylation would produce compounds having the claimed therapeutic activity against steatohepatitis (p. 11). Applicant asserts that the rejection does not provide a reason to expect that the modified peptide would acquire therapeutic efficacy against steatohepatitis. Id.
Applicant asserts that “The Examiner’s position that the simple modification of one known element for another is not supported”; e.g., acetyl group of Chen with a fatty acid) (reply at p, 12). Examiner expressly notes that this argument was never raised in the instant rejection. Applicant appears to refer to the separate/different 103 rejection (Rom et al (U.S. 2021/0315963), in view of Zhang et al (Current Medicinal Chemistry 19:1602-1618 (2012)) and Resh (Prog Lipid Res. 63:120–131 (2016)- withdrawn herein).
With regard to claim 61, applicant asserts that Table 1 lists numerous lipids used for peptide acylation and “nothing in Resh or in the combination directs a person of ordinary skill to select arachidonoyl, or to pair it with GGL, for the treatment of steatohepatitis (p. 12). Applicant asserts hindsight analysis based on applicant’s disclosure. Id.
The new 103 rejection herein more clearly sets forth the rationale for treating steatohepatitis comprising administering an N-acyl GGL or GGdL peptide.
Regarding Applicant’s comments relating to PPARα activity and the cited references not teaching such activity, it is noted that the features upon which applicant relies are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Examiner expressly notes that the matter of simple modification as relating to an acetylation group was never raised in the instant rejection (Applicant reply at p. 12). Applicant appears to refer to the separate/different 103 rejection (Rom et al (U.S. 2021/0315963), in view of Zhang et al (Current Medicinal Chemistry 19:1602-1618 (2012)) and Resh (Prog Lipid Res. 63:120–131 (2016), withdrawn herein.
Regarding the Resh reference and “numerous peptides”, Table 1 recites 8 fatty acids commonly used in protein acylation, ranging in length from 8 carbons to 20 carbons. Eight (8) fatty acids is not deemed to constitute a “numerous” quantity.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Maintained
Specification- maintained, in part
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. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Response to Arguments
Applicant did not address this part of the objection in the reply filed 6/30/2026.
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 all will the boy 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 14, 53-55, 57, and 61-64 remain/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 37, 38, 41, 42, and 50-53 of copending Application No. 17266897 (hereinafter referred to as “the ‘897 application”), in view of Zhang et al (Current Medicinal Chemistry 19:1602-1618 (2012)- previously cited) and Resh (Prog Lipid Res. 63:120–131 (2016)- previously cited). The rejection is maintained from the office action mailed 4/02/2026, but has been amended to reflect claims filed 6/30/2026.
This is a provisional nonstatutory double patenting rejection.
The instant application claims are drawn to a method of treating steatohepatitis in a subject in need thereof, comprising administering a pharmaceutically effective amount of at least one N-acyl amino acid product to the subject in need thereof, wherein the N-acyl amino acid product has a fatty acid component and an amino acid component, wherein the amino acid component is glycine-glycine-leucine or glycine-glycine-D-leucine (claim 14). The instant application further claims wherein the fatty acid component is an omega 3 fatty acid (claim 53); metabolite of an omega 3 fatty acid (claim 54); the amino acid component is a peptide (claim 57); amino acid component is GGL or GGdL; specific N-acyl amino acid products, e.g., N-oleoyl GGL (claim 61); the steatohepatitis is nonalcoholic or alcoholic, or alcoholic liver disease (claim 62); decreases liver fat, decreases inflammatory status, decreases injured hepatocytes, and decreases atherosclerotic plaques (claim 63); and trading mitigates one or more of cirrhosis and hepatocellular carcinoma (claim 64).
Claim 37 of the ‘897 application is drawn to a method for treating liver disease in a mammalian subject in need thereof comprising administering to the subject at least one tripeptide selected from Gly-Gly-Leu or Gly-Gly-dLeu, or a pharmaceutically acceptable salt thereof, wherein the mammalian subject does not have diabetes, and wherein the mammalian subject has liver disease and wherein the liver disease is fatty liver, steatohepatitis, non-alcoholic fatty liver disease (NAFLD), or non-alcoholic steatohepatitis (NASH), wherein the administering reduces the abundance of Clostridium in the gut microbiota of the subject and reduces hepatic expression of CCL5. Claim 38 of the ‘897 application recites the treatment is for fatty liver or the prevention, delay, or reduction of a condition caused by the fatty liver, selected from angina, myocardial infraction, stroke, arteriosclerosis, and pancreatitis. The claims recite that the treatment decreases hepatic TG cholesterol levels (claims 41-42). Claims 50 and 51 of the ‘897 application recite that the method comprises stabilization/production of the NAFLD activity score (NAS) in a subject; slowing the progression of, stabilizing, or reducing the steatosis component of NAS, slowing the progression of, stabilizing, or reducing the lobular inflammation component of NAS, slowing the progression of, stabilizing, or reducing the hepatocyte ballooning component of NAS, or any combination thereof. Claim 53 of the ‘897 application recites the method further comprises administering ace second therapeutic agent recite from a Markush grouping.
Although the claims of the co-pending ‘897 application recite administering Gly-Gly-Leu or Gly-Gly-dLeu to treat steatohepatitis, the claims do not expressly recite a N-fatty acid component.
Zhang et al (Current Medicinal Chemistry 19:1602-1618 (2012)) teach that lipidation is a post-translational modification of proteins that is also found its use in designing peptide drugs. The presence of a lipid group in peptides modulates their hydrophobicity, secondary structures and self-assembling propensities while retaining their abilities to bind to target receptors. Lipidation improves peptides’ metabolic stability, membrane permeability, bioavailability, and changes peptides’ pharmacokinetic and pharmacodynamic properties (abstract; pp. 1602-1609). Zhang et al disclose lipidation strategies in peptide drug design, the effects of the chain length and anchor position of fatty acids in peptide lipidation, the physicochemical and biological properties or peptides, and the synthesis strategies for peptide lipidation. Id.
Resh is a review article discussing fatty acylation of proteins. Table 1 discloses lipids used in a peptide/protein fatty acylation. Lipids include but are not limited to myristate, palmitate, stearate, and arachidonic acid (Table 1).
It would have been obvious to one of ordinary skill in the art to improve pharmacological and pharmaceutical properties of the Gly-Gly-Leu or Gly-Gly-dLeu peptides of the ‘897 application, using the lipidation strategies taught by Zhang et al. The skilled artisan would have recognized that Resh taught fatty acids that could be used in the acylation methods of Zhang et al.
Accordingly, instant claims 14, 57, and 61 are rendered obvious., e.g., N-arachidonoyl-Gly-Gly-Leu.
Regarding claims 53-55, Zhang et al and Resh taught polyunsaturated fatty acids (PUFA), as well as omega 3 fatty acids, and metabolites thereof.
Regarding claim 62, claim 37 of the ‘897 application recites that the liver disease is nonalcoholic steatohepatitis. Regarding claims 63 and 64, claims 38, 41, 42, 50, and 51, recite treatment of the fatty liver, decreases in cholesterol and triglyceride levels, and stabilizing/reducing steatosis and intralobular inflammation.
Accordingly, claims 14, 53-55, 57, and 61-64 are rendered obvious.
Response to Arguments
Applicant did not traverse the rejection. Instead, applicant requested that the rejection be held in abeyance (reply filed 6/30/2026 at p 12).
While a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP 714.02). Until a proper Terminal Disclaimer is filed and approved by the Office, the rejection is maintained.
Claims 14, 53-55, 57, 58, 61, and 63 remain/are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 28, 30, and 38-41 of copending Application No. 18163773 (hereinafter referred to as “the ‘773 application”), in view of in view of Zhang et al (Current Medicinal Chemistry 19:1602-1618 (2012)) and Resh (Prog Lipid Res. 63:120–131 (2016)). The rejection is maintained from the office action mailed 4/02/2026, but has been amended to reflect claims filed 6/30/2026.
The ‘773 is a CON of Application No. 17266897 (the ‘897 application).
This is a provisional nonstatutory double patenting rejection.
The instant application claims are drawn to a method of treating steatohepatitis in a subject in need thereof, comprising administering a pharmaceutically effective amount of at least one N-acyl amino acid product to the subject in need thereof, wherein the N-acyl amino acid product has a fatty acid component and an amino acid component, wherein the amino acid component is glycine-glycine-leucine or glycine-glycine-D-leucine (claim 14). The instant application further claims wherein the fatty acid component is an omega 3 fatty acid (claim 53); metabolite of an omega 3 fatty acid (claim 54); the amino acid component is a peptide (claim 57); amino acid component is GGL or GGdL; specific N-acyl amino acid products, e.g., N-oleoyl GGL (claim 61); the steatohepatitis is nonalcoholic or alcoholic, or alcoholic liver disease (claim 62); decreases liver fat, decreases inflammatory status, decreases injured hepatocytes, and decreases atherosclerotic plaques (claim 63); and trading mitigates one or more of cirrhosis and hepatocellular carcinoma (claim 64).
Claim 38 of the ‘773 application is drawn to a method of treating atherosclerosis, the method comprising administering to a subject in need thereof, and therapeutically effective amount of a glycine-containing tripeptide molecule Gly-Gly-Leu or Gly-Gly-dLeu, or a pharmaceutically acceptable salt thereof, wherein the mammalian subject has atherosclerosis and does not have diabetes ore prediabetes, wherein the administering increases hepatic expression of fatty acid oxidation genes comprising PPARα and CPTI1a relative to baseline, wherein the administering reduces plasma LDL cholesterol levels, wherein the administering reduces hepatic triglyceride content and hepatic total cholesterol levels in the subject. Claim 30 of the ‘773 application recites wherein the subject has a complication of atherosclerosis e.g., myocardial infarction, arteriosclerosis, … or chronic kidney disease. Claim 38 of the ‘897 application recites the method further comprises administering ace second therapeutic agent recite from a Markush grouping. The method increased expression of ABCG5 and ABCG8 (claim 39); reduces plasma MCP-1 (claim 40); and suppresses NF-KB signaling (claim 41).
Although the claims of the co-pending ‘773 application recite administering Gly-Gly-Leu or Gly-Gly-dLeu to treat atherosclerosis (also reducing hepatic triglyceride content, cholesterol levels), the claims do not expressly recite a N-fatty acid component.
The teachings of Zhang et al and Resh are set forth above.
Accordingly, instant claims 14, 57, and 61 are rendered obvious., e.g., N-arachidonoyl-Gly-Gly-Leu.
Regarding claims 53-55, Zhang et al and Resh taught polyunsaturated fatty acids (PUFA), as well as omega 3 fatty acids, and metabolites thereof.
Regarding claim 63, claim 28 of the ‘773 application recites administering GGL or GGdL reduces atherosclerotic plaque burden, reduces plasma LDL cholesterol levels, reduces hepatic triglyceride content and cholesterol levels.
Accordingly, claims 14, 53-55, 57, 61, and 63 are rendered obvious.
Response to Arguments
Applicant did not traverse the rejection. Instead, applicant requested that the rejection be held in abeyance (reply filed 6/30/2026 at p 12).
While a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP 714.02). Until a proper Terminal Disclaimer is filed and approved by the Office, the rejection is maintained.
Conclusion
No claims are allowed.
Claims 14, 53-55, 57, and 59-64 are pending. Claims 59 and 60 are withdrawn.
Claims 14, 53-55, 57, and 61-64 are rejected.
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/KRISTINA M HELLMAN/ Examiner, Art Unit 1654
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