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 .
DETAILED ACTION
Claims 8-17 are pending
Claim 11 is withdrawn from consideration
Claims 8-10 and 12-17 and are under consideration in the instant office action.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 8 (in part), 9-10 12 and 13-17) and the following species in their response dated 06/08/2026 is acknowledged.
Specie 1 Applicants elect the following compound of formula IV, Claims 8 and 13-17 read on the elected compound
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Upon further consideration, the election of specie requirement is withdrawn and the claims 8-10 and 12-17 are examined for all he species they encompass.
Examination of the claims are conducted to the extent they read on the elected species. Claims 8 (in part) , 11 and claims 14-17 (in part) drawn to the method of using compound of formula (II) is withdrawn from examination as being drawn to a nonelected specie.
Claims 8-10 and 12-17 are under examination and the requirement for restriction is made final.
Priority
This application is a U.S. National phase application under 35 U.S.C 371 of PCT application PCT/US2022/038905, filed 7/29/2022, which claims priority under 35 U.S.C 119 (e) from provisional application serial No. 63227926 filed 7/30/2021.
Claim Rejections - 35 USC § 112
The following is a quotation of the second paragraph of 35 U.S.C. 112:
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 8 and 12 are rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 8 and 12 are vague and indefinite because the claim as written is not clear and it is impossible to ascertain the metes and bounds of the limitations in the claim as there is a discrepancy between compounds of formula (III) as recited in claim 8 which are thenopyridinones shown below.
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And the exemplified compounds of formula (III) in claim 12 which are thiazolopyrimidinones as follows:
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. Accordingly, applicants are recommended to amend the claims to clarify their invention.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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 8-10 and 12-17 are rejected under 35 U.S.C. 112, first paragraph, , because the specification, while being enabling for the method of inhibiting SLC26A3 gene with the specific three compound of formula (I) recited in claim 10, specific 2 compounds of formula (III) recited in instant claim 12 and specific 3 compounds of formula (IV) recited in claim 13 is (I) not enabled for the method of treatment of each and every condition, disorder or disease associated with SLC26A3-mediated anion exchange in a subject by administration of each and every compound that is encompassed by the general formulas of (I), (III) and (IV) and (II) not enabled for prevention of any and every condition, disorder or disease associated with SLC26A3-mediated anion exchange including constipation and hyperoxaluria exchange in a subject by administration of each and every compound that is encompassed by the general formulas of (I), (III) and (IV)
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention:
The rejected invention is drawn to a method of preventing or treating a condition, disease, or disorder associated with SLC26A3 -mediated anion exchange in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I), (III) and (IV)
Breadth of claims:
The claims are drawn to methods of preventing and treating a patient suffering from any disease, condition or disorder associated with LC26A3 -mediated anion exchange with various compounds which fall under the general formulas of (I) (III) or (IV)
. First with regards to the formulas recited in instant claim 8, Each of these formulas of (I), (III) and (IV) t encompasses a large number of possible structural components for each variable of the compound of formula recited in instant claim 8 and as such combinations of the various variables recited in the claims would yield many thousands of compounds.
Secondly the term conditions, diseases and disorders associated with SLC26A3 anion exchange is very broad. Mutations in SLC26A3 causes a congenital chronic diarrhea which is an autosomal recessive disorder, a rare disease which can be fatal. It is also involved in Inflammatory bowel disease which includes crohn’s disease , irritable bowel syndrome and ulcerative colitis, they SLC26A3 is also involved in intestinal symptoms of cystic fibrosis. As instantly claimed, the conditions include chronic idiopathic constipation (CIC), opioid-induced constipation (OIC), constipation-predominant irritable bowel syndrome (IBS-C), CF-associated constipation, meconium ileus, distal intestinal obstruction syndrome, calcium oxalate kidney stone disease, enteric hyperoxaluria, or primary hyperoxaluria. Instant claims are drawn to preventing and treating any of these conditions in addition to constipation and hyperoxaluria.
The instant claims are drawn to preventing any and every disease disorder or condition which are mediated by SLC26A3 anion exchange. . The term "prevention' can be construed broadly as either prevention of the increase in clinically evident condition, disease or disorder associated with SLC26A3 anion exchange or preventing the onset of a preclinically evident stage of any of these conditions in individuals at risk. In other words, the instant claims are drawn to a method of preventing all preclinical stages of any and all stages of condition, disease or disorder associated with SLC26A3 anion exchange which includes any undetectable stages of the condition, As mentioned above some of these conditions are congenital and is impossible to be prevented.
The State and Predictaility in the art, and relative skill of those in the art:
“[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.” As discussed above, the instantly claimed invention pertains to method of treating bacterial infection with compounds of formula I which are alleged by the Specification to be useful for that purpose. At the time the instant application was filed, it would have been known by those of ordinary skill in the art that due in large part to the strict requirement of complementarity between a compound and its corresponding binding site on a target receptor or enzyme - compounds, in the vast majority of cases, demonstrate a remarkably high correlation between their structure, specificity and ability to produce a pharmacological effect. At the same time, it would have also been generally assumed that two compounds with similar chemical properties would exhibit similar biological effects. Thus, given a series of compounds that are shown to exert an activity of interest (or given a target of interest), the ordinarily skilled artisan would have expected that a limited genus of related compounds (e.g., compounds exhibiting near equal molecular shapes and volumes, approximately the same distribution of electrons, and similar physical properties such as hydrophobicity, etc.) would interact with the given target to elicit a related biological response. The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicants’ invention would generally be an oncologist or cancer researcher. That factor is outweighed, however, by the unpredictable nature of the art. It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.), Nationwide Chemical Corporation, et al. v. Wright, et al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances), Ex parte Sudilovsky 21 USPQ 2d 1702 (Appellant's invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable).
Once a compound has been identified by ligand based and/or structure based drug design methods as potentially binding to the target molecule, it must be evaluated. However, as discussed by Anderson (Chem and Biol 10:787-797, 2003), “it is important to consider that the ranking assigned by the scoring function is not always indicative of a true binding constant, since the model of the target:ligand interaction is inherently an approximation. Usually, several molecules which scored well during the docking run are evaluated in further tests since even the top scoring molecule could fail in vitro assays… Finally, leads are brought into the wet lab for biochemical evaluation” (Page 794, Column 1). By that point, as noted by Thiel (Nature Biotechnol 2:513-519, 2004), “libraries are small and hit rates are on the order of one in ten” (Page 517, Column 2). This low level of predictability is not surprising considering that even minor structural changes can, and frequently will, drastically alter or eradicate a parent compound’s ability to modulate the activity of a specific receptor or enzyme. Indeed, modifying even a single atom in a compound can dramatically change the compound’s overall structure and - even though complementarity in one portion of the compound might be improved by the chemical revision - the overall binding or activity might be severely compromised. With regards to SLC26A3 mediated disease, the main condition mediated by mutation in this gene is congenital chloride diarrhea. As taught by Wedenoja et al. (Human Mutation, Vol.32, no 7, 715-722, 2011). , Congenital chloride diarrhea (CLD) is an autosomal recessive disorder caused by mutations in the solute carrier family 26 member 3 (SLC26A3) gene disrupting the epithelial Cl_/HCO3 transport in the ileum and colon (abstract). They disclose that In addition to colon cancer, reducedSLC26A3 expression may play a role in the pathogenesis of ulcerative colitis, and reduction of SLC26A3 promoter activity by the inflammatory mediator interferon-gamma (IFN-g) may contribute to the pathogenesis of intestinal inflammation (page 716, col.1, 3rd para). Therefore in terms of preventing and treating every condition, disease or disorder mediated by this gene with any single agents is not known in the art and is highly unpredictable.
The skilled artisan would view the synthesis of every possible variation of the compounds encompassed by formula and treatment and prevention of every SLC26A3-mediated diseases, condition or disorder as requiring much experimentation.
Amount of guidance/Existence of working examples:
More importantly, there are only data showing that specific compounds of formula (I). (III) and (IV) as recited in claims 10, 12 and 13 in the method of inhibiting the SLC26A3 gene. Of the compounds instantly claimed, there is activity of two of the compounds (demonstrating extracellular action of these inhibitors) and data showing the blockage of intestinal oxalate absorption with just one of compound A270 (not encompassed by the instantly claimed formulas). There is no data demonstrating the possible treatment of any of the instantly claimed SLC26A3 diseases, disorders or conditions associated with SLC26A3-anion exchange, let alone data demonstrating the prevention of any of these conditions, diseases or disorders.
Absence of working examples is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP 2164.
The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, one of skill in the art would not accept the assertion that a majority of the compounds encompassed by the claims would be effective in treating any and every disease, disorder or conditions mediated by SLC26A3-anion exchange, or that the explicitly disclosed compounds would be effective in treating or preventing any of these diseases.
Genentech Inc. vs. Nova Nordisk 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" (42 USPQ 2d 1001, Fed. Circuit 1997).
Accordingly, the instant claims 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 reasonable assurance of success
Conclusion
Claims 8-10 and 12-17 are rejected. No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7 am to 4 pm..
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAVITHA M RAO/ Primary Examiner, Art Unit 1691
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