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 .
This action takes into consideration discussions with Attorney (Interview summary filed 9/11/2025) and subsequent request from Attorney for office action.
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 1-11, 15 and 13-14 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for few possibilities of the claimed formula (I) (herein after formula), does not reasonably provide enablement for large number of possibilities for the formula. For example, it is not seen where in the specification enabling disclosure is found for compounds wherein R1 is not 2-amino-4-pyrimidinyl or R7 is other than H. Also there is no disclosure on how to make solvates of the formula. As discussed further below, these are only examples. 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.
The determination that "undue experimentation" would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the relevant factual considerations.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4) amount of direction provided by the inventor; (5) the level of predictability in the art; (6) the existence of working examples; (7) quantity of experimentation needed to make or use the invention based on the content of the disclosure; and (8) relative skill in the art.
All of the factors have been considered with regard to the claims, with the most relevant factors discussed below.
The claimed formula contains large number of variables layered with substituents layered on substituents encompassing wide variety and number of conceivable structures that find little support in the specification. These substituents and hence the compounds of given formula are drawn to species that vary widely in physical and chemical properties such as size, molecular weight, stereochemistry, logP, acidity, basicity, etc. These factors are known in the art (see multiple references cited below) to greatly influence biological properties, for example, binding interaction between target protein and small molecule and art recognized concepts relating to productive small molecule-macromolecule interaction. Working examples with respect to ‘how to make and use’ aspects of the invention are consistent with this art-acknowledged concepts.
Consider for example, the variable R1. All working example with respect to m in
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and the position of attachment to R1 to rest of the molecule is such that R1 is 2-amino-4-pyrimidinyl and m is 0. The generic scheme at page 21 and the working example at pages 46-47 (Pd catalyzed Stille coupling) is limited to the use of previously known starting materials (for 2-amino-4-pyrimidinyl R1 with m being 0). The specification is silent with respect to starting materials needed for other possibilities such as 2-amino-5-pyrimidinyl with m = 1, 2 or 3. The mechanistic details of Stills coupling also limit what R groups in
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are feasible, because for example R = any halogen such as Br would be incompatible with the Pd insertion step in Stille coupling. This is consistent with the disclosure in the specification as the working examples are limited to R = F, because C-F is normally not-susceptible to, oxidative addition of Pd that cleaves C-halogen bond needed to make the discrete C-Pd intermediate.
Likewise, the only working example for X variable compounds contains
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(made by a reductive amination reaction), not any and all
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Similarly there is no working example for R7 or R6 being other than H. It is not that any combination of R groups recited cannot be made, rather the issue is whether undue effort would be needed to make (and predictably use; see more on the use aspect below) While numerous chemistry Text Books do give the impression that organic chemical reactions proceed smoothly, in real-life, organic chemical reactions are capricious. The unpredictability in organic chemical art is high in spite of the high skill level in the area. The state of the art of organic chemical synthesis is closer to what is described by Dorwald, who states, “..Even the most experienced chemist will not be able to foresee all potential pitfalls of a synthesis, especially so if multifunctional, structurally complex intermediates must be prepared.… the outcome of organic reactions is highly dependent on all structural features of a given starting material, and unexpected products may readily be formed...” Dorwald F. A. Side Reactions in Organic Synthesis, 2005, Wiley: VCH, Weinheim pg. IX of Preface pg. 1-15.
As to use prong of 112-1 requirement: The biological data for the few tested compounds are disclosed at page 85. While all are deemed active as per Table 1, at page 82, the actual % inhibition data (last column) for similar compounds do vary. Also the large number of disease-states (see claims 13 and 15 as well as the use of laundry list of additional agents as per claim 15) just do find support in the specification. This is consistent with the fact that biological properties are unpredictable and are ultimately tide to the chemical structures. See “Role of the Development Scientist in Compound Lead Selection and Optimization” by Venkatesh, J. Pharm. Sci. 89, 145-154 (2000) (p. 146, left column). Likewise, J. G. Cannon, Chapter Nineteen in Burger's Medicinal Chemistry and Drug Discovery, Fifth Edition, Volume I: Principles and Practice, Wiley-Interscience 1995, pp. 783-802, 784, teaches many caveats in analog design such as
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That productive small-molecule-protein interaction requires specific structural requirement such as size for binding partners, is one of commonsense. For example, the specification does provide working examples with R=F. Note that while the size of H and F is close, Br and I are considerably larger than H or F. There is limited structural guidance such as pharmacophore definition disclosed in the specification to guide one of skill in the art to choose the combination of the variables that would provide for predictable use. Again, enablement is a two prong (make and use) requirement.
There is a substantial gap between what is taught in the specification and what is being claimed. For these reasons, one skilled in the art would be faced with undue amount of research. The specification lacks disclosure sufficient to make and use the invention, in predictable manner, commensurate with the scope of the claims.
The claims are also drawn to solvates, yet the numerous examples presented all failed to produce a solvate, since no data provided for the disclosed compounds indicate formation of solvate. For example, see NMR data at page 50, 51, 58 onto 60. Solvates cannot be simply willed into existence For examples the isolation of the compounds all involve concentration of dissolved compounds. As such the molecules were exposed to solvents before there were freed from solvate forming solvents. As was stated in Morton International Inc. v. Cardinal Chemical Co., 28 USPQ2d 1190 "The specification purports to teach, with over fifty examples, the preparation of the claimed compounds with the required connectivity. However ... there is no evidence that such compounds exist.., the examples of the '881 patent do not produce the postulated compounds.., there is ... no evidence that such compounds even exist." The same circumstance appears to be true here. There is no evidence that solvates of these compounds actually exist; if they did, they would have formed. Hence, applicants must show that solvates can be made, or limit the claims accordingly. g) The state of the art is that is not predictable whether solvates will form or what their composition will be. In the language of the physical chemist, a solvate of organic molecule is an interstitial solid solution. This phrase is defined in the second paragraph on page 358 of West (West, Solid State Chemistry and Its Applications, john Wiley & Sons, 1984). The solvent molecule is a species introduced into the crystal and no part of the organic host molecule is left out or replaced. In the first paragraph on page 365, West (Solid-State Chemistry) says, "it is not usually possible to predict whether solid solutions will form, or if they do form what is their compositional extent". Thus, in the absence of experimentation one cannot predict if a particular solvent will solvate any particular crystal. One cannot predict the stoichiometry of the formed solvate, i.e. if one, two, or a half a molecule of solvent added per molecule of host. In the same paragraph on page 365 West (Solid State Chemistry) explains that it impossible to make meta-stable non-equilibrium solvates, further clouding what Applicants mean by the word solvate. Compared with polymorphs, there is an additional degree of freedom to solvates, which means a different solvent or even the moisture of the air that might change the stabile region of the solvate. h) The breadth of the claims includes all of the hundreds of thousands of compounds of formula (I) as well as the presently unknown list of solvents embraced by the term "solvate". Thus, the scope is broad.
The issue here is predictable formation of solvates.
Note that in University of Rochester v. G.D. Searle & Co., 68 USPQ2d 1424 at 1438, the screening for over 600 compounds was deemed to be undue. Applicant’s scope far exceeds this number. The specification must teach how to make and use the invention, not teach how to figure out for oneself how to make and use the invention. In re Gardner, 166 USPQ 138 (CCPA 1970). Therefore, one skilled in the art could not make or use the claimed invention without undue experimentation.
MPEP 2164.01(a) states, “A conclusion of Iack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. ln re Wright, 999 F.2d 1557,1562, 27 USPQ 2d 1510, 1513 (Fed. Cir. 1993).'' That conclusion is clearly justified here. Thus, undue experimentation would be required to make and use Applicants' invention.
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.
Claims 1-11, 15 and 13-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 18267222 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are drawn to obvious variants as explained below:
The difference between the claimed formulae in the conflicting claims is the possibilities corresponding to R1. R1 in instant case is pyrimidinyl and in the instant case of ’222 it is pyridinyl. Pyrimidinyl and pyridinyl fall under the scope of generic term ‘heteroaryl’, ostensibly interchangeable, as per the definition of the many R variables decorating the same invariable portion of the claimed formulae in the conflicting claims.
Same invariable formulae with same substituents
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Likewise, (likewise for the same chemistry rationale as above) claims 1-11, 15 and 13-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 18267202 (reference application).
Instant base claim R1 = pyrimidinyl
18267202 base claim R1 = pyrazolyl
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-11, 15 and 13-14 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-17 of copending Application No. 18267177 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625