DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Acknowledgement is made of original (1-2, 9, 12, 15, 19, 51), amended (4, 10-11, 18, 24, 37, 39, 41, 52-53, 55-56, 62), cancelled (3, 5-8, 13-14, 16-17, 20-23, 25-36, 38, 40, 42-50, 54, 57-61, 63-64), claims filed on April 18, 2024. Claims 1-2, 4, 9-12, 15, 18-19, 24, 37, 39, 41, 51-53, 55-56, 62 are pending in instant application.
Priority
The instant application is a 371 National Stage Entry of PCT/US2022/023481 filed on April 5, 2022 which claims benefit to domestic provisional application No. 63/171,342 filed on April 6, 2021.
Information Disclosure Statement
The information disclosure statements filed on November 6, 2023; January 18, 2024; April 18, 2024 have been considered except where lined through.
Claim Rejections - 35 USC § 112
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.
Claims 53, 55, 62 are 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 inhibiting GPR119 in vitro, does not reasonably provide enablement for any condition or disorder involving the gut-brain axis associated with GPR119 activity. 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.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the nature of the invention,
2- the breadth of the claims,
3- the state of the prior art,
4- the predictability of the art,
5- the amount of direction or guidance provided
6- the presence or absence of working examples,
7- the quantity of experimentation necessary, and
8- the relative skill of those in the art.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Undue experimentation is required by one skilled in the art to determine enablement of the instant disclosure as claimed due to the following:
The nature of the invention (1) and the breadth of the claims (2)
The nature of the invention and breadth of claim(s) 53 is the treatment of a condition or disorder involving the gut-brain axis associated with GPR119 activity broadly in a subject (claim 53) or those diseases specifically listed in claim 56.
The specification does not define “treatment”. The broadest reasonable interpretation includes simply not worsening.
The specification does not define what conditions or disorders involving the gut-brain axis associated with GPR119 activity are encompassed or excluded, but merely lists lengthy potential embodiments covering a diverse range of pathologies (see instant spec. at p. 1 ¶[0002] and p. 8 ¶[0017]):
“central nervous system (CNS) disorders including mood disorders, anxiety, depression, affective disorders, schizophrenia, malaise, cognition disorders, addiction, autism, epilepsy, neurodegenerative disorders, Alzheimer' s disease, and Parkinson's disease, Lewy Body dementia, episodic cluster headache, migraine, pain; metabolic conditions including diabetes and its complications such as chronic kidney disease/diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, and cardiovascular disease, metabolic syndrome, obesity, dyslipidemia, and nonalcoholic steatohepatitis (NASH); eating and nutritional disorders including hyperphagia, cachexia, anorexia nervosa, short bowel syndrome, intestinal failure, intestinal insufficiency and other eating disorders; inflammatory disorders and autoimmune diseases such as inflammatory bowel disease, ulcerative colitis, Crohn' s disease, psoriasis, celiac disease, and enteritis, including chemotherapy-induced enteritis or radiation-induced enteritis; necrotizing enterocolitis; diseases/disorders of gastrointestinal barrier dysfunction including environmental enteric dysfunction, spontaneous bacterial peritonitis; functional gastrointestinal disorders such as irritable bowel syndrome, functional dyspepsia, functional abdominal bloating/distension, functional diarrhea, functional constipation, and opioid-induced constipation; gastroparesis; nausea and vomiting; disorders related to microbiome dysbiosis, and other conditions involving the gut-brain axis.”
Notably, encompassed in the list are pathologically opposing conditions (e.g. obesity and anorexia).
Page 75 of the specification says “subject” encompasses mammals, and does not define in finite terms what is included or excluded as a subject. The broadest reasonable interpretation includes a patient population of anything, including cells.
The state (3) and predictability (4) of the art
MPEP § 2164.05(a) states if a publication demonstrates that those of ordinary skill in the art would not find that a particular invention was not enabled years after the filing date, the publication would be evidence that the claimed invention was not possible at the time of filing.
In regards to treating specific diseases with GPR119 agonists, Jones1 teaches GPR 119 agonists are viable candidates for treating type 2 diabetes (see Jones at Abstract) see instant spec. at p. 1 ¶[0002] “type 2 diabetes”). Overton2 teaches a GPR119 agonist for treating obesity (see Overton at Abstract) (see instant spec. at p. 1 ¶[0002] “obesity”).
In regards to treating any metabolic disorder associated with GRP119, Cornall3 teaches activating GRP119 results in weight loss (see Cornall at p. 491 at Figure 2). The prior art does not reasonably inform an artisan how a GRP119 agonist could treat anorexia, a disease encompassed by claims 53, 55 see instant spec. at p. 1 ¶[0002] “anorexia”).
In regards to non-enabled conditions or disorders encompassed, Scott4 teaches GPR119 agonists can induce seizures (see instant spec. at p. 1 ¶[0002], “seizures”) in mice (see Scott at Abstract), which would not lead an artisan to believe they are a viable class of drugs for treating epilepsy, a condition known in the art to be characterized by seizures.
Further, regarding claim 53, a method of treating any condition or disorder involving the gut-brain axis associated with GPR119 activity includes diseases and conditions not yet discovered and not yet discovered to be responsive to an agonist of GRP119. It would certainly require undue experimentation to discover the enabled embodiments encompassed by claim 53.
The prior art provides enablement for treating diseases of instant claim 56 with a GPR119 agonist, recognizing high unpredictability in the art.
The amount of direction or guidance provided (5) and the presence or absence of working examples (6)
The specification provides the following embodiments:
Activation Assay – tests all 115 claimed species in hGRP119 expressing cells (see instant spec at pp. 139-141 Table 2)
The specification provides enablement for inhibiting GRP119.
Nowhere in the specification is it explained how such conditions or diseases listed in claims 53 or 55-56 are to be prevented through the administration of the claimed compounds. Also, it is not explained in the art or applicant’s disclosure how the following diseases (including encompassed pathologically opposing diseases) are ameliorated or their symptoms reduced by the method of claim 53:
central nervous system (CNS) disorders including mood disorders, anxiety, depression, affective disorders, schizophrenia, malaise, cognition disorders, addiction, autism, epilepsy, neurodegenerative disorders, Alzheimer' s disease, and Parkinson's disease, Lewy Body dementia, episodic cluster headache, migraine, pain; metabolic conditions including chronic kidney disease/diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, and cardiovascular disease, , obesity, dyslipidemia,; eating and nutritional disorders including hyperphagia, cachexia, anorexia nervosa, and other eating disorders; inflammatory disorders and autoimmune diseases such as inflammatory bowel disease, ulcerative colitis, Crohn' s disease, psoriasis, celiac disease, and enteritis, including chemotherapy-induced enteritis or radiation-induced enteritis; necrotizing enterocolitis; diseases/disorders of gastrointestinal barrier dysfunction including environmental enteric dysfunction, spontaneous bacterial peritonitis; functional gastrointestinal disorders such as irritable bowel syndrome, functional dyspepsia, functional abdominal bloating/distension, functional diarrhea, functional constipation, and opioid-induced constipation; gastroparesis; nausea and vomiting; disorders related to microbiome dysbiosis, and other conditions involving the gut-brain axis.
Therefore, the full scope of treatment in the methods of claim 53, 55, 62 are not enabled.
The quantity of experimentation necessary (7) and the relative skill of those in the art (8)
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. Because of the unknown predictability in the art (as discussed above) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that compounds of Formula I could be used as GRP119 agonists for treating diseases specifically listed in claims 53, 55, 62
Brenner v. Manson states "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent protection' is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" (Brenner v. Manson 383 U.S. 519, 536, 148 USPQ 689, 696 (1966), cited in Genentech Inc. vs. Nova Nordisk 42 USPQ 2d 1001, Fed. Circuit 1997).
As noted above, little experimentation provided is drawn to treatment of conditions listed in claims 53, 55, 62. A review of the state of the art fails to GPR119 agonists are useful as therapeutic treatment as claimed (e.g. all metabolic disorders associated with GPR119). Determining if compounds of Formula I would be therapeutic for any particular disease state would require careful analysis and replicability of a composition comprising a compound of Formula I, formulation into a suitable dosage form, assay testing to correlate clinical efficacy, identifying off-targets, determining if which species are capable of crossing the blood-brain barrier for relevant diseases (e.g. for Alzheimer’s or Parkinson’s), subjecting to animal trials, and subjecting to clinical trials.
All this is undue experimentation given the limited guidance and direction provided by Applicants.
Conclusion
Accordingly, the inventions of claims 53, 55, 62 do not comply with the enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Suggested Amendment
Examiner suggests amending claim 53 to include the limitations of claim 56.
Allowable Subject Matter
Claim 56 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.
Claims 1-2, 4, 9-12, 15, 18-19, 24, 37, 39, 41, 51-53, 55-56, 62 appear to be free of the prior art.
The closest prior art appears to be WO 2013074388 A1 to Edmondson5 or WO 2010/004347 A1 to Bertam6.
Edmondson teaches structurally similar GPR119 agonists (see Edmondson at Abstract) to instant Formula I, but notably lack the Y-K limitations required by instant Formula I (not bicyclic heterocycles, monocyclic heterocycles do not contain 2 Ns, K structural limitations not met or no substituent even present). Bertram teaches compound 28 (see Bertram at p. 41) which corresponds with instant Formula I when W is 6-membered monocyclic heteroaryl specifically pyrimidine substituted with one Re and Re is halogen specifically chlorine, R4-R11 are hydrogen, r is 3, R1-R2 are hydrogen, X is -O-, A is phenyl, n is 2, and both Ra are C1-6 alkyl specifically methyl, but notably differs in a missing CH2 between instant A and C=O, and the identity of Y.
Edmondson
Claim 19
Bertram
Compound 28
Instant App
Formula I
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88
188
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130
122
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148
310
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No reasonable suggestion or motivation was found to modify a prior art species to arrive at an instantly claimed compound or compound of instant Formula I.
Conclusion
Claims 53, 55, 62 are rejected.
Claim 56 is objected to.
Claims 1-2, 4, 9-12, 15, 18-19, 24, 37, 39, 41, 51-52 are allowed.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Jones et. al. "GPR 119 agonists for the treatment of type 2 diabetes" Expert Opin Ther Patents 2009, 19, 10, 1339-1359. DOI: 10.1517/13543770903153878. Hereinafter Jones.
2 Overton et. al. "Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents" Cell Metabolism 2006, 3, 3, 167-175. DOI: 10.1016/j.cmet.2006.02.004. Hereinafter Overton.
3 Cornall, L. "Is GPR119 agonism an appropriate treatment modality for the safe amelioration of metabolic diseases?" Expert Opinion on Investigational Drugs 2013, 22, 4, 487-498. DOI: 10.1517/13543784.2013.775245. Hereinafter Cornall.
4 Scott et. al. "Circumventing seizure activity in a series of G protein coupled receptor 119 (GPR119) agonists" J Med Chem 2014, 57, 21, 8984-8998. DOI: 10.1021/jm5011012. Hereinafter Scott.
5 Published May 23, 2013. Cite 158 on the IDS filed 11/6/23. Hereinafter Edmondson.
6 Published January 14, 2010. Cite No. 073 in the IDS filed 11/6/23. Hereinafter Bertram.
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