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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) were submitted on 9/23/2022, 9/25/2024, and 7/14/2025 before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 1-26 are pending, filed 9/7/2022. Claims 1-26 are under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 20 and 25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 20, claim 20 refers to Examples recited in the specification, without stating a figure or table. MPEP 2173.05(s) states: “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
It is not clear as to which examples claim 20 refers and furthermore, as described in MPEP 2173.05(s), claims should ideally be complete in themselves. Consequently, claim 20 is rejected.
Regarding claim 25, the phrase "for example" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Line 8 of claim 25 uses the phrase (e.g. cancer treatment) which is a stand-in for “for example”. Similarly, line 22 has various disorders listed after “brush border enzyme deficiencies” in parentheses. Line 24 has various disorders listed after “defects of membrane carriers”. Line 27 has various disorders listed after “enzyme deficiencies”. Line 28 has various disorders listed after “lipid/lipoprotein metabolism defects”. Line 29 has various disorders listed after “defects of enterocyte differentiation or cellular polarization”. Line 31 has various disorders listed after “defects of enteroendocrine cells”. All of these phrases are effective stand-ins for “for example” and it is unclear whether the limitations following the phrase are part of the claimed invention.
Regarding the term “diarrheal diseases” in claim 25, it is not clear whether it refers to “congenital diarrheal diseases” from the specification, or something else.
Claim 25 recites “diarrheal diseases” twice and “chronic diarrhoeal diseases”. It is not clear if this is the same group of diseases or if some difference is intended.
Claim 25 recites intestinal insufficiency more than once. It is not clear if this is the same group of diseases or if some difference is intended.
Claim 25 recites malabsorption disorders more than once. It is not clear if this is the same group of diseases or if some difference is intended.
Claim 25 recites intestinal failure more than once. It is not clear if this is the same group of diseases or if some difference is intended.
Claim 25 recites obesity more than once. It is not clear if this is the same group of diseases or if some difference is intended.
Claim 25 recites diabetes more than once. It is not clear if this is the same group of diseases or if some difference is intended.
Claim 25 recites inflammatory bowel disease more than once. It is not clear if this is the same group of diseases or if some difference is intended.
Claim 25 recites insulin resistance more than once. It is not clear if this is the same group of diseases or if some difference is intended.
Claim 25 recites celiac disease more than once. It is not clear if this is the same group of diseases or if some difference is intended
Therefore, claim 25 is rejected.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 25 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for promoting intestinal recovery and nutritional status of patients with malabsorption disorders, intestinal failure, intestinal insufficiency, improvement of mucosal barrier function, amelioration of gut inflammation, celiac disease, congenital and acquired digestion and malabsorption syndromes, mucosal damage, hyperglycemia during enteral and parenteral nutrition therapy in patients with intestinal failure, acid-induced intestinal injury, arginine deficiency, obesity, chemotherapy-induced enteritis, diabetes, fat malabsorption, steatorrhea, gastric ulcers, gastrointestinal barrier disorders, Parkinson’s disease, sepsis, bacterial peritonitis, bowel trauma, bowel ischemia, mesenteric ischemia, short bowel syndrome, necrotizing enterocolitis, neonatal feeding intolerance, NSAID-induced intestinal damage, total parenteral nutrition damage to the gastrointestinal tract, neonatal nutritional insufficiency, radiation-induced enteritis, radiation-induced damage to the intestines, mucositis, pouchitis, ischemia, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, insulin resistance, hyperglycemia, glucose intolerance, and brush border enzyme deficiencies, glucose-galactose-malabsorption, fructose malabsorption, Fanconi-Bickel syndrome, congenital chloride/sodium diarrhoea, Lysinuric protein intolerance, primary biliary malabsorption, cystic fibrosis, chylomicron retention disease, hypobetalipoproteinemia, abetalipoproteinemia, microvillous atrophy, Tufting enteropathy, trichohepatoenteric syndrome, congenital malabsorptive diarrhoea, anendocrinosis, and protein-convertase 1/3 deficiency, does not reasonably provide enablement for treatment of any possible gastrointestinal and metabolic disease, any possible diarrheal disease, any possible chronic inflammatory bowel disorder, any possible inflammatory disorder, any possible gastrointestinal injury, any possible autoimmune disease, any possible food allergy, any possible chemotherapy-associated tissue damage, necrotizing pancreatitis, Acrodermatitis enteropathica, hereditary pancreatitis, congenital pancreas lipase deficiency, familiar haemophagocytic lymphohistiocytosis type 5, any possible nutritional insufficiency, any possible defect of membrane carriers, any possible enzyme deficiencies, any possible lipid/lipoprotein metabolism defects, any possible defects of enterocyte differentiation or cellular polarization, any possible defect of enteroendocrine cells, or any possible congenital diarrheal disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
The broader members of the list are quite broad. Examples: any possible inflammatory disorder or any possible autoimmune disease.
(B) The nature of the invention;
The invention is an oral GLP receptor agonist.
(C) The state of the prior art;
GLP-1 agonists are an extremely well-studied and well-understood family of molecules. GLP-1 agonists are known to have efficacy against a wide spectrum of diseases, conditions, and disorders. Brown et al. (Brown, et al. Peptides 100: 61-67 (2018)), for example, discloses a wide variety of physiological effects, including insulin regulation, glucagon regulation, appetite regulation, gastrointestinal motility, and blood pressure regulation (Brown et al., page 62, Table 1). GLP-1 agonists have been shown to efficacy for conditions that would be hard to predict a priori such as Parkinson’s as discussed by Hölscher et al. (Hölscher, et al. Neuropharmacology 136: 251-259 (2018), Abstract) or healing mucosal damage as disclosed by Bang-Berthelsen et al. (Bang-Berthelsen, et al. Inflammatory Bowel Diseases 22.9: 2078-2097 (2016), page 2090, col. 2, para. 3). A review of the available literature yielded the above enabled conditions.
(D) The level of one of ordinary skill;
A person of ordinary skill in the art in the field of fusion proteins is usually at least a Master’s level education.
(E) The level of predictability in the art;
Protein-protein interactions are generally unpredictable. Compounds that target metabolic processes frequently have off-target effects.
(F) The amount of direction provided by the inventor and the existence of working examples and the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Applicant provides many structural examples and data that shows their efficacy as GLP-1 or GLP-2 agonists. However, this data in and of itself does not show enablement for all the recited conditions and disorders. Consequently, the prior art is relied upon to show enablement for treating the recited conditions and disorders. Given the time and cost of a drug trial for treatment of a condition, a large amount of experimentation is required to show enablement for the conditions not enabled by the prior art.
As noted in the above analysis, Applicant relies upon the prior art to supply enablement for the conditions and disorders recited by claim 25. While many of these conditions did appear in a survey of the prior art, such broad topics as any possible inflammatory disorder, any possible gastrointestinal injury, any possible autoimmune disease, any possible food allergy, etc., were not found to be supported by the prior art. Consequently, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims and claim 25 is rejected.
Regarding claim 26, this claim reduces the treatment target to Tufting enteropathy, against which GLP-1 agonists are enabled. Consequently, claim 26 is not included in this rejection. Claim 26 is allowable because it is directed to a novel and non-obvious compound of claim 1 for use in a method for treating an disorder for which the compound is enabled.
Closest Prior Art
Claim 1 of the present application recites the following formulae:
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As compared to the available prior art, these formulae have three primary points of novelty. First, is the “R” group located on the N-terminal end of the formula. R is further disclosed to be:
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Such a ring “Q”, located at the N-terminal of the peptide, is not disclosed by the available prior art.
Second, the identity of the residues in positions AA10a and AA11a for formula 1a and positions AA11 and AA14 for formula 2a. In the prior sequences, such as those disclosed by Wisniewski et al. (Wiśniewski, et al. Journal of Medicinal Chemistry 59.7: 3129-3139 (2016)), this region is typically “LAAR”. In the case of formula 1a, AA10a is Lys or Glu, not Leu, Wa is Ala Ala as normal, but AA11a is Aib, Lys, Glu, or Asp, not Arg. In the case of formula 1b, AA11 is LysR or Glu, not Leu, AA12 and AA13 are both Ala as normal, but AA14 is Aib or Lys, not Arg. Consequently, the prior art sequences do not read on these positions, nor provide a person of ordinary skill in the art reasoning to make such mutations.
Third, prior art regarding GLP-1 agonists do not make use of lactam bridges as required by Applicant claim 1. The properties of lactam bridges were well-understood in the prior art as described by Taylor et al. (Taylor, et al. Peptide Science: Original Research on Biomolecules 66.1: 49-75 (2002). However, the prior art does not provide guidance on which residues of the GLP-1 peptide should be targeted for bridging, and therefore does not disclose various bridges recited by Applicant’s claims.
Allowable Subject Matter
Claims 1-19 and 21-24 are directed towards compounds that are free of the prior art as described above in “Closest Prior Art”. The specification discloses a representative number of examples and activity claimed in claims such 22 is fully enabled by said examples. Therefore, these claims are allowable as currently claimed. Claim 26 is allowable because it is directed to a novel and non-obvious compound of claim 1 for use in a method for treating an disorder for which the compound is enabled.
Conclusion
Claims 20 and 25 are rejected.
Claims 1-19 and 21-24 are allowable.
Claim 26 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to David Paul Bowles whose telephone number is (571)272-0919. The examiner can normally be reached Monday-Friday 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID PAUL BOWLES/Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654
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