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 .
Claim Status
Claims 1, 2, 4-14, 16, 17, and 19 were previously pending.
A non-final rejection office action was mailed 21 May 2026.
In response to that 21 May 2026 office action, Applicant filed an Amendment/Request for Reconsideration on 21 August 2026.
In that 21 August 2026 Amendment/Request for Reconsideration, Applicant amended claims 13 and 19, cancelled claims 1, 2, 4-12, and 17, and added claims 21-26.
Therefore, claims 13, 14, 16, 19, and 21-26 are now pending and under examination.
Priority
Examiner acknowledges Applicant’s claim to the following priority:
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Withdrawn Claim Rejections
Applicant has amended the scope of now independent claim 13, further limiting the scope of the claimed liver diseases in the method of treatment. Therefore, all previous claim rejections are moot and hereby withdrawn.
New Claim Objections/Rejections
Applicant’s claim amendments have necessitated the following new claim objections/rejections:
Claim Objection - Warning
Applicant is advised that should claim 9 be found allowable, claim 24 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 13, 14, 19, and 21-26 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (cited in previous office action as US 2018/0186853 A1, published: 05 July 2018) in further view of Boland (“Resolution of NASH and hepatic fibrosis by the GLP-1R/GcgR dual-agonist Cotadutide via modulating mitochondrial function and lipogenesis,” published: 21 May 2020).
The teachings of Kim were previously presented. Specifically, Kim teaches:
Regarding claim 13 –
Kim discloses ‘General Formula 1’ represented by SEQ ID NO: 45 as pictured below:
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([0024]).
Kim discloses ‘General Formula 2’ represented by SEQ ID NO: 46. ‘General Formula 2’ is a narrower embodiment of ‘General Formula 1’ and depicted below:
Y-Aib-QGTF-X7-SD-X10-S-X12-Y-L-X15-X16-X17-R-A-X20-X21-F-V-X24-W-L-M-N-T-X30
([0158], emphasis added).
In the above formula, the bold areas represent locations that differ from the currently claimed General Formula 1 and require a wildcard selection to arrive at the currently claimed General Formula 1. However, the limitations of the wildcard selections include the choice of amino acid residue which allows arrival at the currently claimed General Formula 1.
Furthermore, Kim discloses a pharmaceutical composition for treating or preventing metabolic syndrome, which contains: i) a peptide including the amino acid sequence of General Formula 1, and ii) at least one compound or material having a therapeutic activity for metabolic syndrome ([0024]). Kim discloses the pharmaceutical composition contains a pharmaceutically acceptable carrier, excipient, or diluent ([0391]).
Finally, Kim discloses the metabolic syndrome treated by General Formula 1 can include nonalcoholic steatohepatitis (NASH) ([0156]).
Kim teaches administering the glucagon derivative to treat certain liver diseases, but Kim does not expressly teach administering the glucagon derivative to treat liver fibrosis. However, this limitation is made obvious in further view of Boland.
Boland teaches treatment of established NASH and hepatic fibrosis using Cotadutide, a dual GLP-1 receptor/glucagon receptor agonist (abstract, p. 1). Boland reports that Cotadutide reduces hepatic inflammation and fibrosis and further identifies a distinct therapeutic contribution of glucagon-receptor agonism to its hepatic effects (abstract, p. 2). Boland further reports that Cotadutide alleviates fibrosis to a greater extent than Liraglutide or Obeticholic acid despite adjustment of doses to achieve comparable weight loss (pp. 1 and 3).
In an ob/ob AMLN model of established NASH, Boland further demonstrates decreases in fibrosis-associated endpoints including hepatic collagen, α-SMA, picrosirius red staining, hydroxyproline, inflammatory/profibrotic gene expression, and histological fibrosis stage following Cotadutide administration (pp. 8-10).
Regarding claim 14 –
Kim discloses a specific conjugate embodiment whereby a glucagon derivative is linked to a biocompatible material capable of increasing in vivo half-life, which correlates to Chemical Formula 1 X – L – F ([0136]). The instantly claimed invention can be formulated from the embodiments disclosed by Kim including:
X: a glucagon derivative represented by SEQ ID NO: 20 ([0130], [0131]) is 100% identical to SEQ ID NO: 20 of the instant application as shown below:
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L: the peptide of SEQ ID NO: 20 and an immunoglobulin Fc are linked by polyethylene glycol (PEG), which contains multiple repeating units of ethylene glycol ([0138]).
F: the peptide is linked to an immunoglobulin Fc region and the conjugate compound is termed a long-acting conjugate capable of extending the half-life of the peptide to which it is linked ([0136], [0140], [0151]).
Finally, Kim discloses the components of the embodiment can be covalently linked ([0371]).
Regarding claims 19, 24, and 26 –
Kim discloses the C-terminus of the peptide including the amino acid sequence of General Formulas 1 or 2 may be amidated ([0127], [0418]).
Regarding claim 21 –
Boland expressly evaluates hepatic inflammation by histopathological scoring and related inflammatory endpoints (pp. 48-49, Figure 6). Boland reports improvement in histological inflammation/NASH activity measures following Cotadutide administration and concludes from histological, biochemical, and transcriptional evidence that Cotadutide mitigates hepatic inflammation (pp. 52-53, Figure 8). Accordingly, reducing a liver inflammation score would have been an expected result/flowed naturally from administering the treatment suggested by Kim and Boland to a subject having fibrotic NASH. Therefore, the Office does not rely upon inherency based solely upon Kim’s weight-loss data; rather, Boland expressly teaches improvement in hepatic inflammatory pathology following dual GLP-1/glucagon receptor agonist therapy.
Regarding claim 22 –
Boland expressly measures liver hydroxyproline content as an endpoint of hepatic fibrosis and reports decreased hepatic hydroxyproline following Cotadutide treatment in an established NASH/fibrosis model (pp. 52-53, Figure 8(f)). Boland further identifies the reduced hydroxyproline, together with reduced collagen and other fibrotic markers, as evidence that Cotadutide improved hepatic fibrosis (p. 9). Thus, the additional limitation of claim 22 is expressly taught by Boland and need not be established through inherency.
Regarding claim 23 –
Boland expressly measures hepatic triglyceride concentration in NASH animals and reports that Cotadutide treatment reduces hepatic triglyceride levels. Figure 7(j) specifically evaluates terminal hepatic triglyceride concentration in the ob/ob AMLN NASH model, while the accompanying results state that hepatic triglyceride levels were reduced following treatment (pp. 7, 50-51). Accordingly, the additional limitation of claim 23 would have been expected from the combined teachings of Kim and Boland.
Regarding claim 25 –
Kim discloses the non-peptide linker, which includes PEG, has a molecular weight of 1 kDa to 100 kDa ([0355]). This range is identical to that which is instantly claimed.
It would have therefore been obvious, before the effective filing date of the claimed invention, to administer Kim’s glucagon receptor-active peptide, including the peptide comprising SEQ ID NO: 20, to a subject having liver fibrosis associated with NASH in order to obtain the known hepatic antifibrotic effect of glucagon-receptor agonist therapy taught by Boland.
One of ordinary skill would have had a reasonable expectation of success in doing so because Kim expressly teaches use of the claimed glucagon derivative for treatment of NASH, while Boland demonstrates that pharmacologic agonism, including the glucagon receptor in NASH, produces improvement in established hepatic fibrosis.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Kim and Boland as applied to claims 13, 14, 19, and 21-26 above, and further in view of Marzioni (“Exendin-4, a glucagon-like peptide 1 receptor agonist, protects cholangiocytes from apoptosis,” published: 01 October 2008) and Little (“Gut microbiome in primary sclerosing cholangitis: A review,” published: 07 June 2020).
Regarding claim 16 –
As previously discussed, Kim teaches glucagon derivative peptides, including the peptide of SEQ ID NO: 20, and long-acting conjugates thereof. Kim expressly teaches that its glucagon derivatives may be used for prevention or treatment of metabolic syndrome, including NASH. Kim specifically describes a long-acting derivative of SEQ ID NO: 20 in which the glucagon derivative is linked through polyethylene glycol to an immunoglobulin Fc region. Kim therefore teaches the peptide-conjugate platform recited by the underlying claims and its administration in the context of liver-associated metabolic disease.
Kim does not expressly teach administration of the glucagon derivative for the treatment of primary sclerosing cholangitis (PSC).
Boland teaches that Cotadutide, a dual GLP-1 receptor/glucagon receptor agonist, improves established NASH and hepatic fibrosis. Boland demonstrates reductions in hepatic fibrosis and inflammatory pathology, and further concludes that dual GLP-1/glucagon receptor agonism provides direct hepatic therapeutic effects beyond those attributable merely to weight loss. Therefore, Boland teaches that pharmacologic activation of the GLP-1 and glucagon receptor pathways can ameliorate inflammatory and fibrotic pathology of diseased liver tissue.
Marzioni teaches the use of the GLP-1 receptor agonist exendin-4 in cholestatic biliary injury (p. 990). Marzioni explains that progression of chronic cholestatic disorders toward ductopenia results from dysregulation of cholangiocyte survival, that cholangiocytes express GLP-1 receptors, and that activation of the GLP-1 receptor enhances the proliferative response to cholestasis (p. 990, 995). Marzioni administered exendin-4 to bile duct-ligated animals subjected to additional hepatobiliary injury and found that exendin-4 prevented the increase in apoptotic cholangiocytes and prevented loss of bile ducts (p. 992). Marzioni concluded that exedin-4 may be effective in slowing progression of cholangiopathies to ductopenia (abstract, p. 990).
Little teaches primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by biliary inflammation and stricturing (abstract). Little further discusses the pathogenesis of PSC as involving inflammatory processes in the liver and biliary tree and describes inflammatory processes that can ultimately lead to fibrosis (p. 2769).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to administer the peptide therapy taught by Kim to a subject having PSC, as identified by Little, in view of the therapeutic teachings of Boland and Marzioni. Little establishes that PSC is a chronic cholestatic liver disease characterized by biliary inflammation and stricturing. Marzioni demonstrates that activation of the GLP-1 receptor in an experimental model of cholestatic biliary injury protects cholangiocytes from apoptosis and preserves bile duct mass, thereby providing evidence that agonist therapy directed to this hormone signaling pathway can ameliorate pathological processes characteristic of cholangiopathies. Boland additionally demonstrates that simultaneous GLP-1 and glucagon receptor agonism produces anti-inflammatory and antifibrotic effects in diseased liver tissue.
Accordingly, one of ordinary skill in the art would have had reason to employ Kim’s glucagon derivative peptide in a subject having PSC in order to obtain the hepatic anti-inflammatory and antifibrotic effects taught by Boland together with the cholangiocyte protective effects taught by Marzioni. The combination would have provided a reasonable expectation of therapeutic benefit because the prior art collectively teaches that PSC is a cholestatic inflammatory biliary disease, that GLP-1 receptor agonism protects cholangiocytes during cholestatic injury, and that dual GLP-1/glucagon receptor agonism improves inflammatory and fibrotic liver pathology.
Response to Applicant’s Arguments
Applicant argues that Kim is limited to treatment of metabolic syndrome and that Kim’s experimental evidence, involving body weight, liver fat, and cholesterol in high-fat-diet-induced obesity models, does not provide a reasonable expectation of success for treatment of liver fibrosis (Remarks, p. 7). Applicant further argues that Kim fails to measure hepatic inflammation, hydroxyproline, or triglyceride content and that such results cannot presumed to be inherent (Remarks, p. 9).
The arguments have been fully considered but are not persuasive against the rejection as presently formulated. The present rejection does not rely upon Kim’s reduction of body weight or hepatic fat as inherently establishing treatment of fibrosis. Rather, Kim expressly teaches administration of the claimed glucagon receptor agonist, including the peptide of SEQ ID NO: 20, for treatment of nonalcoholic steatohepatitis. Boland independently teaches that glucagon receptor agonist therapy in established NASH improves hepatic inflammation and fibrosis, and further demonstrates reductions in collagen-related endpoints, hepatic hydroxyproline, histologic fibrosis, and hepatic inflammatory pathology.
Boland further teaches that Cotadutide alleviated fibrosis to a greater extent than Liraglutide or Obeticholic acid even when dosing was adjusted to achieve similar weight loss, and attributes a distinct hepatic therapeutic contribution to glucagon receptor signaling. Thus, the relied upon antifibrotic teaching of Boland is not merely a consequence inferred from weight reduction.
One of ordinary skill, having been taught by Kim to administer the presently recited glucagon derivative for NASH and by Boland that dual GLP-1/glucagon receptor agonist therapy improves established NASH-associated hepatic fibrosis, would have had reason to employ Kim’s glucagon derivative in a subject having liver fibrosis. One of ordinary skill would have had a reasonable expectation of obtaining therapeutic improvement in the fibrotic liver pathology.
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.
US Patent 10,696,725 B2 (date of patent: 30 June 2020)*
*The published application of US Patent 10,696,725 B2, US 2018/0186853, was used as prior art in the 35 USC 103 claim rejections as discussed above
Claims 13, 14, 19, and 21-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 13, and 14 of U.S. Patent No. 10,696,725 B2 (hereinafter ‘725) in further view of Boland (cited above). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
US 10,696,725 Claims
Instant Claims
Reasoning
1, 13, 14
13, 14, 19, and 21-26
General Formula 2 of ‘725 and the possible wildcard embodiments are identical to General Formula 1 of instant claim 14. Furthermore, ‘725 discloses the peptide of General Formula 1 is used in a method to treat liver disease (nonalcoholic steatohepatitis).
SEQ ID NO: 33 of ‘725 is identical to instant SEQ ID NO: 33
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SEQ ID NO: 44 of ‘725 is identical to instant SEQ ID NO: 44
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Claims 1, 13, and 14 of ‘725 are drawn to a peptide used to treat liver disease and further embodiments as discussed above. In view of Boland, as discussed above in the previous rejection, the claims of ‘725 render obvious instant claims 13, 14, 19, and 21-26.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 13, and 14 of U.S. Patent No. 10,696,725 B2 (hereinafter ‘725) in further view of Boland, Marzioni, and Little (cited above).
The teachings of Boland, Marzioni, and Little are discussed above. One of ordinary skill in the art would have had reason to employ the glucagon derivative peptide of ‘725 in a subject having PSC in order to obtain the hepatic anti-inflammatory and antifibrotic effects taught by Boland together with the cholangiocyte protective effects taught by Marzioni. The combination would have provided a reasonable expectation of therapeutic benefit because the prior art collectively teaches that PSC is a cholestatic inflammatory biliary disease, that GLP-1 receptor agonism protects cholangiocytes during cholestatic injury, and that dual GLP-1/glucagon receptor agonism improves inflammatory and fibrotic liver pathology.
US Patent 11,135,271 B2 (date of patent: 05 October 2021)
Claims 13, 14, 19, and 21-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,135,271 B2 (hereinafter ‘271) in further view of Kim and Boland (cited above). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
Claim of US 11,135,271
Instant Claims
Reasoning
1-10
13, 14, 19, and 21-26
‘271, in claims 1-10, is drawn to a peptide comprising the amino acid sequence of General Formula 1. ‘271 is further drawn to the peptide of General Formula 1 represented by SEQ ID NOs: 16 and 17, which is identical to instant SEQ ID NOs: 16 and 17 respectively as shown below:
SEQ ID NO: 16
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SEQ ID NO:17
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‘271 claims only a composition and not the method of treating liver disease.
Kim also discloses a peptide of General Formula 1 that is used to treat a liver disorder. Kim further discloses the peptide of SEQ ID NOs: 16 and 17, also identical to both ‘271 and the instant application SEQ ID NOs: 16 and 17, is used to treat liver disorders including NASH.
Claims 1-10 of ‘271 are drawn to a peptide used to treat liver disease and further embodiments as discussed above and in further view of the express teachings of Kim. Therefore, instant claims 13, 14, 19, and 21-26 are made obvious by claims 1-10 of the ‘271 patent in further view of Kim.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,135,271 B2 (hereinafter ‘271) in further view of Kim, Boland, Marzioni, and Little (cited above).
The teachings of Boland, Marzioni, and Little are discussed above. One of ordinary skill in the art would have had reason to employ the glucagon derivative peptide of ‘271 in a subject having PSC in order to obtain the hepatic anti-inflammatory and antifibrotic effects taught by Boland together with the cholangiocyte protective effects taught by Marzioni. The combination would have provided a reasonable expectation of therapeutic benefit because the prior art collectively teaches that PSC is a cholestatic inflammatory biliary disease, that GLP-1 receptor agonism protects cholangiocytes during cholestatic injury, and that dual GLP-1/glucagon receptor agonism improves inflammatory and fibrotic liver pathology.
US Patent 11,142,559 B2 (date of patent: 12 October 2021)
Claims 13, 14, 19, and 21-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 13-18 of U.S. Patent No. 11,142,559 B2 (hereinafter ‘559) in further view of Kim and Boland (cited above). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
US 11,142,559 Claims
Instant Claims
Reasoning
1-8 and 13-18
13, 14, 19, and 21-26
General Formula 2 of ‘559 and the possible wildcard embodiments are identical to General Formula 1 of instant claim 14. Claimed embodiments of the ‘559 peptide, represented by SEQ ID NOs: 2-11, 13-15, and 18-44, are identical to those sequences currently claimed in the instant application.
‘559 additionally claims the peptide of General Formula 1 is covalently linked to an immunoglobulin Fc region by polyethylene glycol.
However, ‘559 claims the composition is used to treat congenital hyperinsulinism not liver disease.
In view of Kim, who discloses an identical General Formula, identical sequences, and an identical conjugate (peptide – linker – immunoglobulin Fc region) to both ‘559 and the currently claimed invention is used to treat liver disease (NASH), and Boland, as discussed above, the composition of ‘559 renders obvious that which is claimed in instant claims 13, 14, 19, and 21-26.
Claims 1-8 and 13-18 of ‘559 are drawn to a peptide used to treat liver disease and further embodiments as discussed above and in further view of the express teachings of Kim and Boland. Therefore, instant claims 13, 14, 19, and 21-26 are made obvious by claims 1-8 and 13-18 of the ‘559 patent in further view of Kim and Boland.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 13-18 of U.S. Patent No. 11,142,559 B2 (hereinafter ‘559) in further view of Kim, Boland, Marzioni, and Little (cited above).
The teachings of Boland, Marzioni, and Little are discussed above. One of ordinary skill in the art would have had reason to employ the glucagon derivative peptide of ‘559 in a subject having PSC in order to obtain the hepatic anti-inflammatory and antifibrotic effects taught by Boland together with the cholangiocyte protective effects taught by Marzioni. The combination would have provided a reasonable expectation of therapeutic benefit because the prior art collectively teaches that PSC is a cholestatic inflammatory biliary disease, that GLP-1 receptor agonism protects cholangiocytes during cholestatic injury, and that dual GLP-1/glucagon receptor agonism improves inflammatory and fibrotic liver pathology.
US Patent 11,261,227 B2 (date of patent: 01 March 2022)
Claims 13, 14, 19, and 21-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,261,227 B2 (hereinafter ‘227) in further view of Kim and Boland (cited above). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
US 11,261,227 Claims
Instant Claims
Reasoning
1-6
13, 14, 19, and 21-26
Claimed embodiments of the ‘227 peptide, represented by SEQ ID NOs: 20, 22, and 27, are identical to those sequences currently claimed in the instant application.
‘227 and instant SEQ ID NO: 20:
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‘227 and instant SEQ ID NO: 22:
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‘227 and instant SEQ ID NO: 27
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‘227 additionally claims the peptide of claim 1 is linked to an immunoglobulin Fc region by polyethylene glycol.
However, ‘227 claims a composition and not a method of treating liver disease.
In view of Kim, who discloses identical peptides and an identical conjugate (peptide – linker – immunoglobulin Fc region) to both ‘227 and the currently claimed invention is used to treat liver disease (NASH), and Boland, as discussed above, the composition of ‘227 renders obvious that which is claimed in instant claims 13, 14, 19, and 21-26.
Claims 1-6 of ‘227 are drawn to a peptide used to treat liver disease and further embodiments as discussed above and in further view of the express teachings of Kim and Boland. Therefore, instant claims 13, 14, 19, and 21-26 are made obvious by claims 1-6 of the ‘227 patent in further view of Kim and Boland.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,261,227 B2 (hereinafter ‘227) in further view of Kim, Boland, Marzioni, and Little (cited above).
The teachings of Boland, Marzioni, and Little are discussed above. One of ordinary skill in the art would have had reason to employ the glucagon derivative peptide of ‘227 in a subject having PSC in order to obtain the hepatic anti-inflammatory and antifibrotic effects taught by Boland together with the cholangiocyte protective effects taught by Marzioni. The combination would have provided a reasonable expectation of therapeutic benefit because the prior art collectively teaches that PSC is a cholestatic inflammatory biliary disease, that GLP-1 receptor agonism protects cholangiocytes during cholestatic injury, and that dual GLP-1/glucagon receptor agonism improves inflammatory and fibrotic liver pathology.
US Patent 11,667,688 B2 (date of patent: 06 June 2023)
Claims 13, 14, 19, and 21-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,667,688 B2 (hereinafter ‘688). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
US 11,667,688 Claims
Instant Claims
Reasoning
1-7
13, 14, 19, and 21-26
The peptides used in the method of treating liver disease (NASH) in ‘688 claim 1 are identical to what is currently claimed.
‘688 and instant SEQ ID NO: 20
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‘688 and instant SEQ ID NO: 22
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‘688 and instant SEQ ID NO: 27
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‘688 and instant SEQ ID NO: 37
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Claims 1-7 of ‘688 are drawn to a peptide used to treat liver disease and further embodiments as discussed above. Therefore, instant claims 113, 14, 19, and 21-26 are made obvious by claims 1-7 of the ‘688 patent and in further view of Kim and Boland.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,667,688 B2 (hereinafter ‘688) in further view of Kim, Boland, Marzioni, and Little (cited above).
The teachings of Boland, Marzioni, and Little are discussed above. One of ordinary skill in the art would have had reason to employ the glucagon derivative peptide of ‘688 in a subject having PSC in order to obtain the hepatic anti-inflammatory and antifibrotic effects taught by Boland together with the cholangiocyte protective effects taught by Marzioni. The combination would have provided a reasonable expectation of therapeutic benefit because the prior art collectively teaches that PSC is a cholestatic inflammatory biliary disease, that GLP-1 receptor agonism protects cholangiocytes during cholestatic injury, and that dual GLP-1/glucagon receptor agonism improves inflammatory and fibrotic liver pathology.
Copending application 17/927,150*
*notice of allowance issued 14 July 2026 and issue fee payment was made 31 August 2026, but patent number has not been assigned.
Claims 13, 14, 19, and 21-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32, 35-36 and 42 of copending Application No. 17/927,150 (hereinafter ‘150) in further view of Kim and Boland (cited above). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
17/927,150 Claims
Instant Claims
Reasoning
32, 35-36 and 42
13, 14, 19, and 21-26
Claimed embodiments of the ‘150 peptide, represented by SEQ ID NOs: 2-11 and 13-45, are identical to those sequences currently claimed in the instant application.
For instance, ‘150 and instant SEQ ID NO: 37
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‘150 Formula 1 is identical to Chemical Formula 1 of the instant application.
However, ‘150 claims a composition and not a method of treating liver disease.
In view of Kim, who discloses identical peptides and an identical conjugate (peptide – linker – immunoglobulin Fc region) to both ‘150 and the currently claimed invention is used to treat liver disease (NASH), and Boland, as discussed above, the composition of ‘150 renders obvious that which is claimed in instant claims 13, 14, 19, and 21-26.
Claims 32, 35-36 and 42 of ‘150 are drawn to a peptide and peptide conjugate used to treat liver disease as discussed above and in further view of the express teachings of Kim and Boland. Therefore, instant claims 13, 14, 19, and 21-26 are made obvious by claims 32, 35-36 and 42 of the ‘150 patent application in further view of Kim and Boland.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32, 35-36 and 42 of copending Application No. 17/927,150 (hereinafter ‘150) in further view of Kim, Boland, Marzioni, and Little (cited above).
The teachings of Boland, Marzioni, and Little are discussed above. One of ordinary skill in the art would have had reason to employ the glucagon derivative peptide of ‘150 in a subject having PSC in order to obtain the hepatic anti-inflammatory and antifibrotic effects taught by Boland together with the cholangiocyte protective effects taught by Marzioni. The combination would have provided a reasonable expectation of therapeutic benefit because the prior art collectively teaches that PSC is a cholestatic inflammatory biliary disease, that GLP-1 receptor agonism protects cholangiocytes during cholestatic injury, and that dual GLP-1/glucagon receptor agonism improves inflammatory and fibrotic liver pathology.
Copending application 18/285,753
Claims 13, 14, 19, and 21-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, and 14-15 of copending Application No. 18/285,753 (hereinafter ‘753) in further view of Kim and Boland (cited above). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
18/285,753 Claims
Instant Claims
Reasoning
1-5, 8, and 14-15
13, 14, 19, and 21-26
Claimed embodiments of the ‘753 peptide and peptide conjugate, represented by SEQ ID NOs: 13-25, 27, 29, 31, 33, and 35-45, are identical in structure and identification number to those sequences currently claimed in the instant application.
‘753 claims the peptide is represented by General Formula 1, which includes potential embodiments of the currently claimed General Formula 1. ‘753 further claims the peptide of General Formula 1 is part of a conjugate represented by Formula 1. ‘753 Formula 1 is identical to Chemical Formula 1 of the instant application.
However, ‘753 claims a composition and not a method of treating liver disease.
In view of Kim, who discloses identical peptides and an identical conjugate (peptide – linker – immunoglobulin Fc region) to both ‘753 and the currently claimed invention is used to treat liver disease (NASH), and Boland, as discussed above, the composition of ‘753 renders obvious that which is claimed in instant claims 13, 14, 19, and 21-26.
Claims 1-5, 8, and 14-15 of ‘753 are drawn to a peptide and peptide conjugate used to treat liver disease as discussed above and in further view of the express teachings of Kim and Boland. Therefore, instant claims 13, 14, 19, and 21-26 are made obvious by claims 1-5, 8, and 14-15 of the ‘753 patent application in further view of Kim and Boland.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, and 14-15 of copending Application No. 18/285,753 (hereinafter ‘753) in further view of Kim, Boland, Marzioni, and Little (cited above).
The teachings of Boland, Marzioni, and Little are discussed above. One of ordinary skill in the art would have had reason to employ the glucagon derivative peptide of ‘753 in a subject having PSC in order to obtain the hepatic anti-inflammatory and antifibrotic effects taught by Boland together with the cholangiocyte protective effects taught by Marzioni. The combination would have provided a reasonable expectation of therapeutic benefit because the prior art collectively teaches that PSC is a cholestatic inflammatory biliary disease, that GLP-1 receptor agonism protects cholangiocytes during cholestatic injury, and that dual GLP-1/glucagon receptor agonism improves inflammatory and fibrotic liver pathology.
Copending application 18/723,147
Claims 13, 14, 19, and 21-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 12, 13, 16-19, and 21-23 of copending Application No. 18/723,147 (hereinafter ‘147) in further view of Kim and Boland (cited above). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
18/723,147 Claims
Instant Claims
Reasoning
1, 2, 12, 13, 16-19, and 21-23
13, 14, 19, and 21-26
Claimed embodiments of the ‘147 peptide and peptide conjugate, represented by SEQ ID NOs: 13, 15, 19, 33, and 36-45, are identical in structure and identification number to those sequences currently claimed in the instant application.
‘147 claims the peptide is represented by General Formula 2, which includes potential embodiments of the currently claimed General Formula 1. ‘147 further claims the peptide of General Formula 2 is part of a conjugate represented by Chemical Formula 1. ‘147 Chemical Formula 1 is identical to Chemical Formula 1 of the instant application.
However, ‘147 claims a method for treating disease requiring drug action in the liver, not specifically a liver disease.
In view of Kim, who discloses identical peptides and an identical conjugate (peptide – linker – immunoglobulin Fc region) to both ‘147 and the currently claimed invention is used to treat liver disease (NASH), and Boland, as previously discussed, the composition of ‘147 renders obvious that which is claimed in instant claims 13, 14, 19, and 21-26.
Claims 1, 2, 12, 13, 16-19, and 21-23 of ‘147 are drawn to a peptide and peptide conjugate used to treat liver disease as discussed above and in further view of the express teachings of Kim and Boland. Therefore, instant claims 13, 14, 19, and 21-26 are made obvious by claims 11, 2, 12, 13, 16-19, and 21-23 of the ‘147 patent application in further view of Kim and Boland.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims claims 1, 2, 12, 13, 16-19, and 21-23 of copending Application No. 18/723,147 (hereinafter ‘147) in further view of Kim, Boland, Marzioni, and Little (cited above).
The teachings of Boland, Marzioni, and Little are discussed above. One of ordinary skill in the art would have had reason to employ the glucagon derivative peptide of ‘147 in a subject having PSC in order to obtain the hepatic anti-inflammatory and antifibrotic effects taught by Boland together with the cholangiocyte protective effects taught by Marzioni. The combination would have provided a reasonable expectation of therapeutic benefit because the prior art collectively teaches that PSC is a cholestatic inflammatory biliary disease, that GLP-1 receptor agonism protects cholangiocytes during cholestatic injury, and that dual GLP-1/glucagon receptor agonism improves inflammatory and fibrotic liver pathology.
Response to Applicant’s Arguments
Applicant argues the prior rejection does not establish treatment of the instantly claimed liver diseases. Applicant’s argument has been considered but is not persuasive against the rejection as presently formulated. The present rejection does not rely solely on Kim to bridge the gap between Kim’s express teachings and treatment of liver disease.
Further, Applicant argues the nonstatutory double patenting rejections be deferred. MPEP § 804 explains that a provisional nonstatutory double patenting rejection should be made and maintained until the rejection has been obviated or is no longer applicable. A complete response to such a rejection requires either a showing that the rejected claims are patentably distinct from the reference claims or the filing of an appropriate terminal disclaimer. The MPEP further states that, because such a response is necessary for further consideration of the rejection, the matter should not be held in abeyance.
Conclusion
Claims 13, 14, 16, 19, and 21-26 are rejected. No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JULIA A. ROSSI/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
