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
Claims 1-20 are pending in the instant application.
Election/Restrictions
This action is in response to an election from a restriction requirement filed May 12th, 2026. There are 20 claims pending and 17 claims under consideration. Claims 16-17 and 20 have been withdrawn as claims directed to a non-elected invention. This is the first action on the merits. The present invention relates to a compound of structural formula (I) as recited at instant Claim 1.
Applicant’s election without traverse of Group I, Claims 1-15 and 18-19 and species election of a single species of a compound of formula (I) as
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in the reply filed August 11th, 2026 is acknowledged. Therefore this restriction is considered proper and thus made FINAL.
The elected species has been found to be free of the prior art. Thus, examination has been extended to all species of a compound of formula (I) as recited at instant Claim 1.
Domestic Benefit
Acknowledgement is made of Applicant’s claim for domestic benefit on the basis of U.S. Provisional Application Nos. 63/466,864 and 63/468,397, filed on May 16th, 2023 and May 23rd, 2023, respectively. Claims 1-15 and 18-19, presently under examination, are fully supported by U.S. Provisional Application No. 63/466,864, and will be evaluated with an effective filing date of May 16th, 2023.
Information Disclosure Statement
The Information Disclosure Statements received on May 16th, 2024, August 5th, 2024, and November 6th, 2024 have been fully considered by the examiner, except where marked with a strikethrough.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Instantly, a hyperlink is provided at the second line of Page 17 of the instant specification.
The abstract of the disclosure is objected to because it is fewer than 50 words in length and insufficiently describes the nature of the chemical compounds claimed herein. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Applicant is reminded of the proper content of an abstract of the disclosure.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which Applicant may become aware of in the specification.
Drawings
Acknowledgement is made of the drawings received on June 17th, 2024. These drawings are acceptable.
Claim Rejections – Improper Markush Grouping
Claims 1-15 and 18-19 are 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 a compound of structural formula (I) 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:
The Markush grouping is directed to compounds of structural formula (I). Structural formula (I) is:
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Wherein the variables R1, R2, R3, and R4 are drawn to a plethora of chemical moieties that are optionally further substituted.
The result is a group of compounds that include polycyclic ring systems that share no significant structural similarity. This grouping includes compounds that are not obvious variants of each other. To this end, defining R1 as
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or
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produces compounds that read on compounds of structural formula (I), but these compounds would demonstrate a lack of significant structural similarity and are not obvious variants of each other. This lack of significant structural similarity is also seen by selecting any of the myriad of definitions by which variables R2, R3, and R4 may be defined.
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.
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 1-15 and 18-19 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 a compound of structural formula (I) in which R1 is
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, R2 is ethyl, ethyl substituted with morpholino, NHBoc, or NH2, or propyl substituted with -O(C)OEt, R3 is methyl, and R4 is propyl, ethyl substituted with morpholinyl, or propyl substituted with -O(C)OEt, or TFA or succinate solvates thereof, does not reasonably provide enablement for compounds of structural formula (I) in which R1, R2, R3, and R4 are otherwise defined, or for solvates that are not TFA or succinate solvates, or hydrates thereof. 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.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to compounds of structural formula (I) or pharmaceutically acceptable salts, solvates, or hydrates thereof.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to compounds of the formula:
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allowing compounds resulting from the myriad combinations of the recited definitions of the variables thereof.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. 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, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
The amount of direction provided and working examples:
The compound core depicted with specific substituents represents a narrow subgenus for which applicant has provided sufficient guidance to make and use; however, the disclosure is not sufficient to allow extrapolation for the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of compounds of structural formula (I) in which R1, R2, R3, and R4 were not defined as stated above.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP 608.01(p).
MPEP § 2164.01(a) states, “A conclusion of lack 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. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). That conclusion is clearly justified here that Applicant is not enabled for making the breadth of compounds claimed.
Claim 14 is 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1977); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQD at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F. 2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of a certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found to not have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Instantly, Claim 14 recites a compound of claim 1 having the structure:
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This compound is not disclosed in the instant specification. Therefore, Claim 14 does not meet the written description requirement.
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 12 and 18-19 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 12 recites the limitation "X is -C(O)OR10, -OR12, or -NR13R14”". There is insufficient antecedent basis for this limitation in the claim, as X and R12 are not defined within the claim, or in Claim 1, from which Claim 12 depends.
Additionally, Claim 12 recites the limitation “The compound of claim 1 of structural formula (II)”. There is insufficient antecedent basis for this limitation in the claim, as structural formula (II) is not recited in Claim 1, from which Claim 12 depends.
Claim 18 is rendered indefinite as it is drawn to “The compound of claim 1 and a compound selected from the group…” Therefore, Claim 18 is drawn to two separate, distinct compounds. Appropriate clarification is required.
Claim 19 is rendered indefinite as it is drawn to “A pharmaceutical composition comprising the compound of claim 18 and a pharmaceutically acceptable vehicle.” Claim 18 is drawn to two distinct compounds, so it is unclear as to what “the compound” is attempting to claim.
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, 3-4, 9-11, and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ali et. al. (“Quantitative Structure-Activity Relationships (QSAR) of Two Series of O-Aryl or N-Aryl O-Ethyl Phosphoramidate and Phosphorodiamidate Fungicides Incorporating Amino Acid Ethyl Esters”, Bull. Environ. Contam. Toxicol., 2000; hereinafter referred to as Ali).
At Page 416, Ali teaches structures of the following formula:
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Entry 7 teaches a compound of this formula in which X is defined a O, R1 is m-Cl, and R2 as H. For clarity of the record, the full structure of this compound is:
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This compound reads on a compound of structural formula (I) as recited at instant Claim 1 when the variables are defined as follows:
R1 is substituted aryl, wherein aryl is phenyl, substituted by halo, as taught at Paragraph [0044] at Page 17 of the instant specification as being a suitable substituent, wherein halo is chloro.
R2 is alkyl, wherein alkyl is ethyl.
R3 is -H.
R4 is alkyl, wherein alkyl is ethyl.
Y is -O-.
Regarding Claim 15, Ali teaches at Page 415, Last Paragraph, that toxicological assessment of the compounds disclosed by adding each compound to potato dextrose-agar medium, and that ethanol was added where necessary for complete solubility.
Claims 1, 9-11, and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ross et. al. (WO 2010/135569 A1; hereinafter referred to as Ross).
At Page 50, Ross teaches a compound of the following structure:
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This compound reads on a compound of structural formula (I) as recited at instant Claim 1 when the variables are defined as follows:
R1 is substituted aryl, wherein aryl is phenyl, substituted by halo, as taught at Paragraph [0044] at Page 17 of the instant specification as being a suitable substituent, wherein halo is chloro.
R2 is aryl, wherein aryl is phenyl.
R3 is alkyl, wherein alkyl is methyl.
R4 is alkyl, wherein alkyl is isopropyl.
Y is -O-.
Regarding Claim 15, at Page 51, Lines 15-16, a solution of this compound is taught in THF.
Claims 1 and 9-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Paz et. al. (“Chemoselective Intramolecular Functionalization of Methyl Groups in Nonconstrained Molecules Promoted by N-Iodosulfonamides”, Organic Letters, 2015; hereinafter referred to as Paz).
At Page S30 of the supporting information, Paz teaches the following compound:
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For clarity of the record, the full structure of this compound is:
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This compound reads on a compound of structural formula (I) as recited at instant Claim 1 when the variables are defined as follows:
R1 is substituted aryl, wherein aryl is phenyl, substituted by halo, as taught at Paragraph [0044] at Page 17 of the instant specification as being a suitable substituent, wherein halo is iodo.
R2 is aryl, wherein aryl is phenyl.
R3 is alkyl, wherein alkyl is isobutyl.
R4 is alkyl, wherein alkyl is methyl.
Y is -O-.
Conclusion
Claims 1-15 and 18-19 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.J.B./Examiner, Art Unit 1624
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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