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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 11/24/2025 is acknowledged. The traversal is on the ground(s) that there would not be serious search burden if all the claims are examined together. This is not found persuasive because Applicant is non-responsive to one or more explanation for search and examination burden, see for example, difference in classification of subject matter.
As per MPEP, non-elected claims will be rejoined, upon finding of the allowability of elected claims.
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, 4, 7, 9, 11-13 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 making some of the compounds of the given formula II, does not reasonably provide enablement for the corresponding hydrates, solvates, nitrogen oxides as well as the large number of possibilities defined for Z of the formula II. 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 specification also does not reasonably provide enablement for making solvates of the claimed compounds. Note hydrate is one of many possible solvates. The specification does not enable any person skilled in the art of synthetic organic chemistry to make the invention commensurate in scope with these claims. The factors to be considered in making an enablement rejection have been summarized above. In the present case the important factors leading to a conclusion of undue experimentation are the absence of any working example of a formed solvate, the lack of predictability in the art, and the broad scope of the claims. There is no working example of any solvate or solvate formed. It is clear, no hydrate or solvate is formed, see for example NMR data, of the compounds made The claims are drawn to solvates, yet the numerous examples presented all failed to produce a solvate, since none of the analytical data provided for the disclosed compounds indicate formation of solvate. These cannot be simply willed into existence. Thus for examples the isolation of the compounds all involve concentration of dissolved compounds, from organic solvents or from water (to make hydrate). 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.
Similarly, there is no method disclosed for making nitrogen oxides. The pictured formula has multiple nitrogens. There is chemistry method disclosed to make oxide(s) of any or all of the nitrogen(s). Likewise, while one of skill in the art would understand what a stereoisomer or tautomer is. Here the invariable structural moiety in the formula II has no stereocenter or possibility of making tautomeric structure. This is not 112-2 vague and indefinite issue. Yes there is possibility for forming stereoisomeric alkyl substituents (for Z variable). There is no working example or how these make any difference to the intended use of the claimed compounds. Note that the 112-1 is a two prong (make and use) requirement.
As to the Z of the formula I.
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. For example it is not seen where in the specification enabling disclosure is found for X4=N and X5=O,S and NH.
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.
Enablement is lacking for the large number of possibilities defined for Z, for example
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Thus Z is defined as large number of groups 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.
Enabling disclosure is found for making amide bonds of from the carboxylic acid corresponding to Y = CH2COOH. While it is acknowledged that making amides from carboxylic acid and amines is elementary organic chemistry exercise, the issue here is the preparation of starting material amine needed for the coupling as defined for the Z. For example, working examples enabled here are for short chain amines and amine substituted small ring systems (4-6 membered) mostly azetidine, further limited with one substituent. Multiple substituents R5, “
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on these do not find support in the specification. Thus X5 of Z for any and ring systems
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with m4 and m5 of 0 to 4 any combination do not have direction, working examples and guidance in the specification. Such possibilities defy commonly accepted elementary organic and medicinal chemistry principles of small molecule-protein/enzyme interaction needed for the intended utility of the claimed compounds (see more on this below). Specification does not provide citations on how to procure such large substituted or unsubstituted amine starting material compounds. According to the U.S. Court of Customs and Patent Appeals in In re
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, De Boer, Eble, and Herr 168 USPQ 99 at 101, "[o]rdinarily no problem in this regard arises since the method of preparing almost all starting materials can be set forth in writing if the materials are not already known and available to the workers in the art, and when this is done the specification is enabling to the public". The 25 working examples found in the specification see pages 47-48 (and also see claim 11) are for making and using Z-Y small structural moieties. That the biological properties of a compound with four membered heterocycle for Z-Y and a compound with 11 or 12 membered heterocycle for Z-Y would be predictably similar is inconstant with art acknowledged medicinal chemistry principles, because biological properties are unpredictable and are ultimately tide to the chemical structure. 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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Also see Note below. 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 commensurate with the scope of the claims. MPEP 2164.01(a) states, “A conclusion of Isaack 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.
Suggestion:
DELETE
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from the claims. Amend Z consistent with enabling disclosure pointed out above.
Note that a double patenting rejection was presented in this office action over the claims of US11679108 for compounds having a single atom change in the bicycle portion of the claimed formula on otherwise overlapping subject matter of compounds in the conflicting claims.
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 1, 4, 7, 12-13 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.
The Z variable in the claimed formula II is improper. Z as per the structure is monovalent. Consistent with this are the possibilities for Z at bottom of claim numbered page 2. The optional substituents R5 defined for Z includes monovalent (OH and F) and divalent group CH, see bottom of page 3 penultimate line
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Divalent CH possibility would amount to dangling valency problem.
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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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625