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 the Claims
Claims 1-5 and 22-39 are pending in the instant application and subject to examination herein.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/2/2024, 01/13/2025 and 03/16/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112(b)
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.
Claim 4 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of claim 4 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: While the alternatives presented in the Markush group of “J1” substituents do share the common purpose of fulfilling the position of “J1” within the structure of the instant formula as claimed in claim 1, the Markush group members do not share a “single structural similarity”. The group of J1 substituents includes disparate structures falling under dozens of Cooperative Patent Classification (CPC) codes, including sulfones (C07C 317/30), aliphatic heterocycles (C07D 205/04), fused-ring condensed heterocycles (C07D 305/14), spiro-condensed heterocycles (C07D 209/54), boronic acid compounds (C07F 5/025), spiro carbocyclic compounds (C07C 2602/50), bicyclo carbocyclic ring systems (C07C 2602/38 and C07C 2602/42), and many others.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claims 26-27 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.
Claim 26 further limits claim 1, regarding a genus of carboxamide compounds, to a method comprising administering the compound of claim 1 to a subject. Claim 27 further limits claim 1 to a method of activating an ion channel in an ocular tissue of a subject, comprising administration of the compound of claim 1 to the subject.
Claim 26 and 27 are indefinite because (1) claim 26 does not provide any purpose for the method (i.e., to treat a condition) and (2) neither claim includes any identification of a population of subject(s) to whom the compound should be administered. A person of ordinary skill in the art would not understand when or to whom the method(s) should be applied in the absence of any purpose or identified patient/subject population.
Claim Rejections - 35 USC § 112(a)
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 1-3, 5 and 23-39 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Specifically, while Applicant appears to be in possession of a body of 178 specific compounds that are exemplified in the instant Specification and representable by structural formula(e) incorporating a central carboxamide group with specific, structurally defined substituents at positions J1-J17, Applicant does not have adequate written description support for the full breadth of the claimed invention as in claim 1, wherein J1 is defined by no more than a variable chemical formula and molecular weight range.
The Invention in General:
Applicant has disclosed an invention in the field of compounds that activate (i.e., agonists of) Transient Receptor Potential Melastatin 8 (TPR-M8), an ion channel, and therapeutic treatments comprising administering said compounds to a subject in need thereof (Abstract).
The Claimed Invention:
Claim 1 is drawn to a genus of compounds bearing a central carboxamide group with variable substituents J1, J2, and J4 with further limitations of each disclosed therein:
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J1 is further defined as “C1-13H2-19N0-2O0-3S0-1B0-1F0-3Cl0-1 comprising 0 to 3 rings and a molecular weight of about 39.0 to about 220.3. No further structural limitation is provided for J1, and therefore this moiety is open to myriad permutations, for example the structure shown below1, hereafter referred to as “structure A” wherein the dashed bond represents the bond to the central carboxamide nitrogen:
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(Exemplary structure in scope of J1 as claimed in instant claim 1)
Structure A, as a moiety, has a chemical formula of CH2N2O3SBF2, 1 ring, and a molecular weight of 171, and clearly falls within scope of the limitations of J1 in instant claim 1. A complete compound within scope of the genus of compounds of claim 1, including structure A is shown below, hereafter referred to as “compound A1”2:
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Exemplary compound A1, while not specifically rendered or claimed in instant claim 1, falls within the scope of the limitations of the genus of compounds claimed in claim 1.
The Supporting Disclosure:
The instant Specification includes structures of 178 exemplary compounds within scope of the genus of compounds as claimed in instant claim 1 (Table 1, paragraph [0051]), wherein the relevant portion of the structure corresponding to J1 includes substituted phenyl rings, monocyclic carbocyclic rings, condensed and spirocyclic carbocyclic ring systems, heterocycles, and other structures. None of the exemplary compounds include a 3,3-dioxo-1,3λ⁶,2,4-oxathiadiazolidine ring bearing a difluoroboryl or any other further substituent as J1.
Applicant further provides general synthetic strategies wherein the J1 moiety bears an amine that will become the carboxamide nitrogen of the final compound, and the J1 precursor compound is reacted with the remainder of the compound structure, which contains an acyl chloride at the proto-carboxamide carbon (paragraph [0096]), or instead contains a carboxylic acid at the proto-carboxamide carbon, in which case the reaction is facilitated by a coupling agent such as a carbodiimide compound (paragraphs [0094] and [0099]). In all these synthetic examples, the relevant J1 moiety must be synthetically available bearing an amine compound.
The Prior Art, and Predictability of the Prior Art:
A search of the Chemical Abstracts Services (CAS) database shows that there is no known compound including a 3,3-dioxo-1,3λ⁶,2,4-oxathiadiazolidine ring bearing a difluoroboryl or any other further substituent, nor any 1,3,2,4-oxathiadiazolidine ring (i.e., without oxo-groups at the sulfur atom). Thus, Applicant’s description of J1 in instant claim 1 is a sub-genus of moieties that can include heretofore unknown structures. Being a completely unknown ring system, the synthesis of a dioxo-1,3λ⁶,2,4-oxathiadiazolidine ring is not predictable at all, let alone bearing the required amine group to enable synthesis of a final compound, such as exemplary compound A1 shown above, according to Applicant’s provided synthetic strategy. The example of a completely unknown structure with unpredictable precursor synthesis that is within scope of the genus of compounds claimed by Applicant in instant claim 1 evidences that Applicant has not fully anticipated the breadth of the genus of J1 moieties encompassed by the nonspecific characterization by chemical formula, number of rings, and molecular weight range as claimed for J1 in instant claim 1, and is not in possession of the full breadth of this genus.
Claims 2-3, 5 and 23-39 depend from claim 1 and do not resolve Applicant’s incomplete possession of the breadth of compounds represented by the genus that includes only a chemical formula, number or rings (or lack thereof) and molecular weight range for the moiety J1.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-5, 22-26, 28-30, 34-37 and 39 are anticipated by Reynolds.
Claims 1-5, 22-26, 28-30, 34-37 and 39 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Reynolds (U.S. PG Pub 2005/0187211 A1).
Claim 1 is drawn to a genus of compounds bearing a central carboxamide group with variable substituents J1, J2, and J4 with further limitations of each. Reynolds discloses a family of N-(substituted-aryl-alkyl)-cycloalkyl carboxamide compounds, including multiple compounds that anticipate the genus of instant claim 1, for example Reynolds’ compounds IIa4-13 and IIa4-34 shown in the table below (paragraph [0184]):
Claim Number(s) of Instant Application
Instant Application
Reynolds
1
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wherein:
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Compound IIa4-1
1
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wherein:
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Compound IIa4-3
Thus, claim 1 is anticipated by the disclosure of Reynolds.
Claims 2-3 and 5 further limit claim 1, each to a narrower genus of compounds, and each is met by Reynolds’ disclosure of compounds IIa4-1 and IIa4-3. Claim 4 further limits claim 1 to a narrower genus of compounds that is met by Reynolds’ disclosure of compound IIa4-3.
Claim 22 is drawn to a Markush group of specific compounds that includes both of the compounds disclosed by Reynolds as IIa4-1 and IIa4-3 (page 9, left column).
Claim 39 further limits claim 1 to an article of manufacture comprising the compound of claim 1 and instructions for use. Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. Applicant is referred to In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004) – See MPEP 2112.01 (III).
Thus, claims 2-5, 22 and 39 are met by the disclosure of Reynolds.
Claim 23 further limits claim 1 to a method of preparing a compound of claim 1, comprising a condensation reaction that includes contacting an acyl precursor compound with an amine precursor compound, as shown in the figure below, wherein the “J3” moiety is OH or Cl:
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Reynolds discloses the synthesis of compound IIa4-1 from the corresponding carboxylic acid and amine precursors, as “Scheme 1” (paragraph [0133]), shown below, thereby fulfilling the limitations of claim 23:
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Claim 24 further limits claim 1 to a composition comprising the compound of claim 1. Since the claim does not require any ingredients beyond the compound of claim 1, this claim is not further limiting to claim 1 and is met by the disclosure of Reynolds.
Claim 25 further limits claim 1 to a pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier. Reynolds discloses that “Compounds of the present disclosure can conveniently be administered in a pharmaceutical composition containing
the compound in combination with a suitable excipient” (paragraph [00140]).
Claim 26 further limits claim 1 to a method, comprising administration of the compound of claim 1 to a subject.
Claim 34 further limits claim 1 to a method of treating an inflammatory disease, comprising administering the compound of claim 1 to a subject in need thereof.
Claim 35 further limits claim 1 to a method of treating a cancer, comprising administration of the compound of claim 1 to a subject in need thereof.
Claim 36 further limits claim 1 to a method of treatment, comprising administration of the compound of claim 1 to a subject in need thereof, wherein the treatment is selected from a Markush group that includes treatment of disease characterized by abnormal growth.
Claim 37 further limits claim 1 to a method of treatment, comprising administration of the compound of claim 1 to a subject in need thereof, wherein the treatment is selected from a Markush group that includes treatment of prostate cancer.
Reynolds discloses that compounds of the invention disclosed therein bind to certain receptors in the TRP (transient receptor potential) ion channel family, and specifically the channel that is alternately called “Trp-p8” or “TRP-M8”, which is typically present at elevated levels in cancers, such as prostate cancer, and that activation of the Trp-p8 (TRP-M8) receptor causes increased calcium flow into cancerous cells and ultimately cell death, and thus that compound disclosed therein are useful for the treatment of cell proliferation diseases or disorders, and stimulated apoptosis (paragraph [0092]). Reynolds also discloses that the compounds of the invention disclosed therein can be used to kill cancer cells, specifically prostate cancer cells and liver cancer cells (paragraph [0088]). Reynolds defines “tumor” as an abnormal benign or malignant mass of tissue that may or may not be inflammatory (paragraph [0079]), and provides an example of inhibiting tumor growth in vivo in mice bearing human prostate cancer tumor(s) comprising administering a compound disclosed therein, including compound IIa4-1 shown in the table above (Example 4, paragraphs [0180]-[0181], and Figure 2).
Thus, claims 26 and 34-37 are anticipated by the disclosure of Reynolds.
Claim 28 further limits claim 1 to a method of modulating a transient receptor potential cation channel subfamily M member 8 (TRPM8) activity, comprising contacting the TRPM8 channel with the compound of claim 1.
Claim 29 further limits claim 1 to a method of modulating an ion channel activity, comprising contacting the ion channel with the compound of claim 1.
Claim 30 further limits claim 1 to a method of modulating a transient receptor potential (TRP) channel activity, comprising contacting the TRP channel with the compound of claim 1.
Reynolds discloses an example of Trp-p8 (TRP-M8) ion channel activation by compounds disclosed therein, including compound IIa4-1 shown in the table above (paragraph [0178] and paragraph [0183], including Table 1).
Thus, claims 28-30 are anticipated by the disclosure of Reynolds.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to W. JUSTIN YOUNGBLOOD whose telephone number is (703)756-5979. The examiner can normally be reached on Monday-Thursday from 8am to 5pm. The examiner can also be reached on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S. Lundgren, can be reached at telephone number (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/W.J.Y./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 IUPAC name: 5-(difluoroboranyl)-3,3-dioxo-1,3λ⁶,2,4-oxathiadiazolidine
2 IUPAC Name: (1R,5R)-2-acetyl-N-[5-(difluoroboranyl)-3,3-dioxo-1,3λ⁶,2,4-oxathiadiazolidin-2-yl]-5-methylcyclohexane-1-carboxamide
3 (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(propan-2-yl)cyclohexane-1-carboxamide
4 (1R,2S,5R)-N-(4-hydroxyphenyl)-5-methyl-2-(propan-2-yl)cyclohexane-1-carboxamide
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