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 1-10 are pending in the instant application.
Priority
Acknowledgement is made of Applicant’s claim for foreign priority based on the CN202110644327.2 and CN202111164489.2 applications filed in the People’s Republic of China on June 9th, 2021 and September 30th, 2021, respectively.
Information Disclosure Statement
The Information Disclosure Statements filed on December 8th, 2023, October 24th, 2024, January 2nd, 2025, February 27th, 2025, May 19th, 2025, and June 16th, 2025 have been fully considered by the examiner, except where marked with a strikethrough.
Drawings
Acknowledgement is made of the drawings received December 8th, 2023. These drawings are acceptable.
Specification
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.
Claim Objections
Claim 7 is objected to because of the following informalities:
Rule 1.141(a) states:
Two or more independent and distinct inventions may not be claimed in one national application, except that more than one species of an invention, not to exceed a reasonable number, may be specifically claimed in different claims in one national application, provided the application also includes an allowable claim generic to all the claimed species and all the claims to species in excess of one are written in dependent form (§ 1.75) or otherwise include all the limitations of the generic claim.
Claim 7 claims a large number of species of the generic claim, but in independent format. Multiple inventions may not be claimed in a single application unless they are species claims which are dependent upon the larger, generic claim. In the past, the Office has held a “reasonable number” to be five (5) species. The present claim contains well over this number of species. One could envision forty pages of species compounds in a single claim which is not dependent upon any genus claim. This would cause undue burden to the Office in examining such a large claim. Therefore, it is recommended that Claim 7 either be dependent from a larger, genus claim, or, that claim 7 incorporate all of the limitations of the genus claim. Applicants are invited to contact the examiner if further clarification is needed. No new matter is permitted.
Appropriate correction is required.
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 1-6 and 8 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 a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, or solvate thereof, does not reasonably provide enablement for a prodrug of a compound of 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.
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 a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug 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 for myriad combinations of the variables recited 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:
With respect to prodrugs, Walther et. al. (“Prodrugs in medicinal chemistry and enzyme prodrug therapies”, Adv. Drug Deliv. Rev., 65-77, 2017; hereinafter referred to as Walther) represents the state of the prior art.
Prodrugs are typically employed when, for example, the parent drug compound has poor aqueous solubility, poor absorption from the gastrointestinal tract into the blood, poor rates of cell entry, among other reasons as outlined at Table 1 at Page 66 of Walther. Design strategy for a prodrug depends on the structural features of the parent drug molecule and availability of the appropriate chemical functionalities that can be used to mask pharmacodynamic activity of the drug through an attachment of a modifying group. Typically, an enzymatic process is relied upon for drug release.
In particular, at Page 67, Walther notes that esters are commonly used as prodrugs due to the ubiquity of esterases in the body and the abundance of hydroxyl and carboxylic acid functionalities in drug compounds.
The amount of direction provided and working examples:
At Page 31 of the instant specification, beginning at Line 25, the term prodrug is disclosed as a compound that is either biologically active or inactive, but when taken in an appropriate matter, undergoes metabolism or chemical reactions in the human body to convert to compounds of formula (I), inclusive of carboxylates, carbonates, phosphates, nitrates, sulfates, and other forms.
This encompasses a broad scope of compounds a person of ordinary skill in the art would readily be able to envisage. In view of Walther, compounds of formula (I) contain a plethora of positions that are suitable for further functionalization for a compound that could operate as a prodrug. Based on the content of the instant disclosure, however, there is no guidance to direct a person having ordinary skill in the art to understand which prodrugs are appropriate, nor would they understand the motivation for doing so.
Applicant has provided no examples of any prodrugs of compounds of formula (I).
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. As referenced above, a person having ordinary skill in the art would need to identify suitable prodrug candidates, determine the metabolites formed when said prodrugs are administered to a host, and confirm compounds of formula (I) are generated as a result of the metabolism of the prodrug.
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.
The specification fails to provide enough support for the broadly claimed prodrugs of compounds of formula (I).
Genentech Inc. v Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person having ordinary skill in the art would have to engage I undue experimentation to determine suitable prodrugs of compounds of formula (I) as instantly recited, with no assurance of success.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 9-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because no process, machine, manufacture, or composition of matter has been positively recited as a limitation of the claim. Per MPEP 2172.05(q), “"Use" claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101 ").”
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 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Booth et. al. (WO 01/70741 A1; cited on Applicant’s Information Disclosure Statement filed October 24th, 2024 hereinafter referred to as Booth).
At Page 15, Booth teaches the following compound as compound 38:
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This compound reads on a compound of formula (I) as recited at instant Claim 1 when the variables are defined as follows:
R1 is C6 aryl substituted with one R6, wherein R6 is 6-membered heteroaryl containing 2 heteroatoms that are each N, substituted with two R”’ substituents, wherein each R”’ substituent is C1 alkyl.
R2 is hydrogen, wherein p is 1.
R3a and R3b are each hydrogen.
R4 is Br.
R5 is C1-alkyl.
r is 2.
At Page 15, Booth teaches the following compound as compound 40:
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This compound reads on a compound of formula (I) as recited at instant Claim 1 when the variables are defined as follows:
R1 is C6 aryl substituted with two R6, wherein R6 is 6-membered heteroaryl containing 2 heteroatoms that are each N, and the second R6 is halogen, wherein the halogen is fluoro.
R2 is hydrogen, wherein p is 1.
R3a and R3b are each hydrogen.
R4 is Br.
R5 is C1-alkyl.
r is 2.
At Page 16, Booth teaches the following compound as compound 47:
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This compound reads on a compound of formula (I) as recited at instant Claim 1 when the variables are defined as follows:
R1 is C6 aryl, substituted by one R6, wherein R6 is unsubstituted 6-membered heterocycloalkyl containing two heteroatoms that are N and O.
R2 is hydrogen, wherein p is 1.
R3a and R3b are each hydrogen.
R4 is Br.
R5 is C1-alkyl.
r is 2.
Regarding instant Claim 8, at Page 6, Lines 3-5, Booth teaches pharmaceutical compositions comprising the compounds noted above.
Claims 1 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Behenna et. al. (US 2018/0044344 A1; cited on Applicant’s Information Disclosure Statement filed December 8th, 2023; hereinafter referred to as Behenna).
At Page 58,Behenna teaches the following compound as example 10:
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This compound reads on a compound of formula (I) as recited at instant Claim 1 when the variables are defined as follows:
R1 is 6-membered heterocycloalkyl containing 1 heteroatom that is N, substituted by one R6, wherein R6 is SO2R7, wherein R7 is C1 alkyl.
R2 is hydrogen, wherein p is 1.
R3a is OH.
R3b is C1 alkyl.
R4 is C1 alkyl, substituted with two halogens, wherein each halogen is fluoro.
R5 is hydrogen.
r is 2.
Regarding Claim 8, at Page 1, Paragraph 0003, Behenna teaches pharmaceutical compositions comprising the above compound.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS Registry File 2624119-27-1 (entered into STN April 1st, 2021; cited on Applicant’s Information Disclosure Statement filed October 24th, 2024; hereinafter referred to as CAS Registry File 1).
CAS Registry File teaches the following compound:
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This compound reads on a compound of formula (I) as recited at instant Claim 1 when the variables are defined as follows:
R1 is 6-membered heteroaryl containing 1 heteroatom that is N, substituted with one R6, wherein R6 is unsubstituted 6-membered heterocycloalkyl containing two heteroatoms that are each nitrogen.
R2 is hydrogen, wherein p is 1.
R3a is hydrogen.
R3b is hydrogen.
R4 is bromine.
R5 is hydrogen.
r is 3.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS Registry File 2414158-91-9 (entered into STN April 16th, 2020; cited on Applicant’s Information Disclosure Statement filed October 24th, 2024; hereinafter referred to as CAS Registry File 2).
CAS Registry File 2 teaches the following compound:
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This compound reads on a compound of formula (I) as recited at instant Claim 1 when the variables are defined as follows:
R1 is 6-membered heterocycloalkyl containing one heteroatom that is nitrogen, substituted by one R6, wherein R6 is SO2R7, wherein R7 is C1 alkyl.
R2 is hydrogen, wherein p is 1.
R3a is C1 alkyl.
R3b is OH.
R4 is bromine.
R5 is hydrogen.
r is 2.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS Registry File 2624132-10-9 (entered into STN April 1st, 2021; cited on Applicant’s Information Disclosure Statement filed October 24th, 2024; hereinafter referred to as CAS Registry File 3).
CAS Registry File 3 teaches the following compound:
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This compound reads on a compound of formula (I) as recited at instant Claim 1 when the variables are defined as follows:
R1 is 6-membered heteroaryl containing 1 heteroatom that is N, substituted with one R6, wherein R6 is unsubstituted 6-membered heterocycloalkyl containing two heteroatoms that are each nitrogen.
R2 is hydrogen, wherein p is 1.
R3a is hydrogen.
R3b is hydrogen.
R4 is bromine.
R5 is hydrogen.
r is 0.
Conclusion
Claims 1-6 and 8-10 are rejected.
Claim 7 is objected to.
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.
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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
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624