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 .
Nucleotide and/or Amino Acid Sequence Disclosures – objection withdrawn
In view of the amendment filed December 19, 2025, this application is in compliance with the sequence rules.
Claim Rejections - 35 USC § 112(b) - withdrawn
The rejection of claims 1-11 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the amendment to the claims filed December 19, 2025.
Claim Rejections - 35 USC § 112(d) - withdrawn
The rejections of claims 8 and 10-11 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, are withdrawn in view of the amendment to the claims filed December 19, 2025.
Claim Rejections - 35 USC § 102 - withdrawn
The rejection of claims 10-11 under 35 U.S.C. 102(1)(a) as being anticipated by Jiang et al. (EP 3447067 A1) is withdrawn in view of the amendment to the claims filed December 19, 2025.
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.
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.
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.
Claims 1 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al. (EP 3447067 A1) in view of Fallowfield et al. (“Pathogenesis and treatment of hepatic fibrosis: is cirrhosis reversible?” Clinical Medicine 2011, Vol 11, No 2: 179–83). This rejection is modified to reflect the amendment filed December 19, 2025.
1. Scope and contents of the prior art
Jiang et al. teach a method of treating hepatic fibrosis comprising administering GLP-1R/GCGR dual target agonist polypeptides (¶¶ [0012], [0013], [0016], [0025], [0027]; Figures 1-3, 6; Examples 2-4). The GLP-1R/GCGR dual target agonist polypeptide derivatives have amino acid sequences that are identical to those recited in instant claim 1. For example, Jiang et al. teach (p. 7):
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which is a GLP-1R/GCGR dual target agonist polypeptide derivative identical to instant compound 1 (SEQ ID NO: 1).
In addition, Jiang et al. teach (p. 13):
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which is a GLP-1R/GCGR dual target agonist polypeptide derivative identical to instant compound 17 (SEQ ID NO: 17).
In addition, Jiang et al. teach (p. 13):
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which is a GLP-1R/GCGR dual target agonist polypeptide derivative identical to instant compound 18 (SEQ ID NO: 18).
In addition, Jiang et al teach (p. 13):
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196
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which is a GLP-1R/GCGR dual target agonist polypeptide derivative identical to instant compound 19 (SEQ ID NO: 19).
In addition, Jiang et al. teach (p. 14):
Compound 37 (SEQ ID NO: 37):
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which is a GLP-1R/GCGR dual target agonist polypeptide derivative identical to instant compound 20 (SEQ ID NO: 20).
2. Ascertaining the differences between the prior art and the claims at issue.
Jiang et al. do not teach that the hepatic fibrosis is caused by viral hepatitis.
3. Resolving the level of ordinary skill in the pertinent art.
Fallowfield et al. review the pathogenesis and treatment of hepatic fibrosis. The authors describe the dangers of hepatitis fibrosis that occur independent of the underlying cause (p. 179, col 1):
Fibrosis, or scarring, of the liver is a generic wound healing response to chronic liver disease regardless of aetiology. Progressive fibrosis eventually evolves to cirrhosis, with fibrotic bands, parenchymal nodules and vascular distortion leading to liver cell dysfunction, portal hypertension (PHT), hepatocellular carcinoma (HCC) and premature death.
The risks of progressive fibrosis, which include death, underscore the need for treating this condition.
Fallowfield et al. teach that liver fibrosis caused by viral hepatitis can be reversed by targeting the underlying infection with antivirals. However, Fallowfield et al. teach that for some patients, especially those who fail to respond to antiviral therapy, there is a need to target the fibrosis directly (p. 181, col 2-3):
However, for patients in whom specific treatment is not possible or successful (e.g. antiviral non-responders), therapies that can slow or reverse fibrosis are necessary (Table 2). In practical terms, the potential to achieve stasis or lack of progression of fibrosis in the face of continued liver injury would be clinically meaningful if liver function was preserved, complications of decompensated cirrhosis reduced or the need for liver transplantation delayed or averted.
Fallowfield et al. teach that anti-fibrosis therapies may include inhibitors of hepatic stellate cell (HSC) activation (Figure 2).
It would have been obvious to apply the method of treating hepatic fibrosis comprising administering GLP-1R/GCGR dual target agonist polypeptides taught by Jiang et al. to hepatic fibrosis caused by viral hepatitis. One of ordinary skill in the art would have been motivated to do so given that Jiang et al. demonstrate that GLP-1R/GCGR dual target agonist polypeptides can significantly inhibit activation of human hepatic stellate cells in vitro, suggesting that active polypeptides have excellent in vitro anti-hepatic fibrosis effect (Example 2). This specific activity would motivate one of ordinary skill in the art to apply the GLP-1R/GCGR dual target agonist polypeptides to viral hepatitis fibrosis because Fallowfield et al. suggests that inhibitors of HSC activation can be used to treat fibrosis regardless of cause including fibrosis caused by viral hepatitis (Figure 2). There would have been a reasonable expectation of success given that Jiang et al. demonstrate that the polypeptides can significantly inhibit CCl4-induced hepatic fibrosis in mice (Example 3).
The resulting method would satisfy all of the limitations of instant claim 1.
Regarding claim 9, Fallowfield et al. teach HPV and HCV (p. 181, col. 2).
Response to Arguments
Applicant's arguments filed December 19, 2025, have been fully considered but they are not persuasive. Applicant traverses the rejection on the grounds that there would have been no reasonable expectation of success to treat hepatic fibrosis caused by hepatitis with the claimed GLP-1R/GCCR dual agonists because 1) Jiang teaches fibrosis caused by NAFLD not by hepatitis, 2) the etiologies and mechanisms of NAFLD and hepatitis-related fibrosis are different, 3) there is no known drug in clinical use that treats both types of fibrosis, and 4) treatment of hepatic fibrosis caused by hepatitis is complex.
The differences between Jiang and Fallowfield and the complexity of the art are acknowledged. However, there is specific teaching in these references that addresses the points raised by Applicant.
Fallowfield et al. corroborates Applicant’s argument that liver fibrosis caused by viral hepatitis is primarily treated and reverses with antiviral therapy. However, Fallowfield et al. go on to state that for some patients, a therapy that targets the fibrosis directly is required (p. 181, col 2-3): “However, for patients in whom specific treatment is not possible or successful (e.g. antiviral non-responders), therapies that can slow or reverse fibrosis are necessary (Table 2). Fallowfield et al. teach that anti-fibrosis therapies may include inhibitors of hepatic stellate cell (HSC) activation (Figure 2). Jiang et al. demonstrate that GLP-1R/GCGR dual target agonist polypeptides have this very mechanism of action. That is, Jiang et al. teach that GLP-1R/GCGR dual target agonist polypeptides can significantly inhibit activation of human HSCs in vitro (Example 2). Therefore, despite the differences between the etiology of NAFLD and hepatitis-related fibrosis and the complexity in the art, there is a specific teaching in the prior art that supports a reasonable expectation of success. The ability of the GLP-1R/GCGR dual target agonist polypeptides to inhibit HSC activation taught by Jiang et al. suggests that these peptides would have an anti-hepatic fibrosis effect because Fallowfield et al. teach that HSC activation inhibitors can be used to treat this condition.
For these reasons, the rejection is maintained.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 7 am - 3 pm.
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/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654