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 45-70 are pending in the instant application.
Claims 1-44 have been canceled.
Election/Restriction
This action is in response to an election from a restriction requirement filed on July 20th, 2026. There are 26 claims pending and 26 claims under consideration. This is the first action on the merits. The present invention relates to a method of treating tinnitus.
Applicant canceled the previously presented claims and with the submission of new Claims 45-70, elects a method of treating tinnitus and the following compound:
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as a single species of formula (I). Claims 45-70 read on this elected group. Applicant did not indicate whether this election was made with or without traverse. As such, the examiner has construed this as an election without traverse. Therefore, this restriction is considered proper and thus made FINAL.
The elected species was found to be free of the prior art. Thus, examination was extended to all species of a compound of formula (I) as recited at instant Claim 45.
Priority
Acknowledgement is made of Applicant’s claim for foreign priority based on the CN201810141153.6, CN201810180543.4, CN201810491114.9, CN201870771964.4, and CN201811408081.3 applications filed in the People’s Republic of China on February 11th, 2018, March 5th, 2018, May 21st, 2018, July 13th, 2018, and November 23rd, 2018, respectively.
Information Disclosure Statement
The Information Disclosure Statements received February 5th, 2025 and September 10th, 2026 have been fully considered by the examiner, except where marked with a strikethrough.
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
Claims 45-47, 49, 53, 55-56, 60, 62, and 63-65 are objected to because of the following informalities:
At the last two lines of Claim 45, the variables “m1” and “n1” are presented as “m1” and “n1”. This variable needs to be recited consistently throughout the claims. This inconsistency is also recited at the last line of Claim 46, the last line of Claim 47, the second to the last line of Claim 49, the last line of Claim 53, the last line of Claim 55, the last line of Claim 56, the last line of Claim 60, the last line of Claim 62, the last line of Claim 63, the last line of Claim 64, and the last line of Claim 65.
Appropriate correction is required.
Claims 48-52, 55, and 57-61 objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only and cannot depend from any other multiple dependent claim. Claim 48 improperly depends from the method of claim 45 and depends from claim 46 to define the instantly recited variables. Claim 49 depends from the method of Claim 48, a multiple dependent claim, and depends from claim 46 to define the instantly recited variables. Claim 50 depends from Claim 49, which is an improper multiple dependent claim and this dependency is not resolved. Claim 51 depends from the method of claim 48, a multiple dependent claim, and from Claim 49 to define the instantly recited variables. Claim 52 depends from the method of Claim 48, a multiple dependent claim, and from Claim 49 to define the instantly recited variables. Claim 55depends from the method of Claim 45 and from Claim 53 to define the instantly recited variables. Claim 57 depends from the method of Claim 45 and from Claim 46 to define the instantly recited variables. Claim 58 depends from the method of Claim 45 and from Claim 49 to define the instantly recited variables. Claim 59 depends from the method of Claim 45, and from Claim 49 to define the instantly recited variables. Claim 60 depends from the method of Claim 45 and from Claim 49 to define the instantly recited variables. Claim 61 depends from the method of Claim 45 and from Claim 60 to define the instantly recited variables. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
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 45-47, 53-54, 56, and 62-68 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 method of treating tinnitus comprising administering a compound of formula (I) in which X is -CR17- in which R17 is either hydrogen or forms a cyclopropyl or epoxide with an adjacent Rz, Y is -S(CH2)n1-,
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,
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,
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, Rx is hydrogen, methyl optionally substituted by methoxy, hydroxy, -(CH2)n1R23R24-, Ry is hydrogen, Rf is hydrogen or methyl, Rz is hydrogen, methyl optionally substituted with nitro, ethyl optionally substituted with nitro, halogen, CF3, cyano, -(CH2)n1S(O)m1-, or two Rz groups form cyclopropyl or epoxide, or Rx and Ry together form a 5-membered heterocycle, R21 is methyl, halogen, 5-6-membered heterocyclyl, 5-membered heteroaryl, or phenyl, wherein the methyl, heterocyclyl, heteroaryl or phenyl are optionally substituted by trifluoromethyl, methyl, halogen, oxo, nitro, cyano, hydroxy, methoxy, 5-membered heteroaryl, -(CH2)n1C(O)OR25-, -(CH2)n1NR25 wherein R25 is methyl or ethyl, n is 1 or 2, and n1 is 0 or 1, does not reasonably provide enablement for a method of treating tinnitus comprising administering a compound of formula (I) in which these variables are otherwise defined. 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 method of treating tinnitus comprising administering a compound of formula (I) as recited at instant Claim 45.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to a method comprising the administration of any compound of formula (I), which is:
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This allows for a method drawn to the administration of any of the myriad of compounds readily envisaged by any combination of the variables recited thereof.
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.
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.
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 of the limited examples to enable the scope of administration of the compounds instantly claimed. Applicant has provided no working examples in which X, Y, R17, Rx, Ry, Rf, Rz, R21, R23 or R25 were defined as anything other than those definitions noted above in the instant application.
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 the 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 administration of these compounds.
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 67-68 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 67 recites the limitation "Z is selected from…" in the first line of the claim, “Ra is selected from…” in the fifth line of the claim, and “Rd is selected from…” in the 13th line of the claim. There is insufficient antecedent basis for these limitations in the claim, as Claim 45, from which claim 6 depends, does not recite the variables Z, Ra, or Rd.
Claim 68 recites the limitation "R15a is selected from…" in the second line of the claim, “R16a is selected from the group…” in the 11th line of the claim, and “R15a and R16a can form…” in the 13th line of the claim. There is insufficient antecedent basis for these limitations in the claim, as Claim 45, from which claim 68 depends, does not recite the variables R15a or R16a.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 46 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 46 fails to further limit Claim 45, from which it depends. Variables R1-R7, R11-R12. R15a-R16b, and R18-R19 replace the variables Rx, Ry, Rf, and Rz recited at Claim 45, but do not limit properly limit the scope thereof.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 45-47, and 64 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Upasani et. al. (WO 2013/056181 A1; hereinafter referred to as Upasani).
At Page 202, Claim 28, Upasani teaches a method of treating a CNS-related disorder comprising administration of any of the compounds of claims 1 to 21. At Claim 29, Upasani teaches the CNS-related disorder can be tinnitus. Beginning at Page 190, Claim 26, Upasani teaches specific compounds as recited at Claim 2. At Page 198, second compound of the second line, Upasani teaches the following compound:
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This compound reads on a compound of formula (I) as recited at instant Claim 45 when the variables are defined as follows:
X is -CR17-, wherein R17 is hydrogen.
Y is
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, wherein n1 is 1.
m is 2, and one Rx is alkyl, wherein alkyl is methyl, and the second Rx is hydroxy.
n is 1.
o is 1, and Rf is alkyl, wherein alkyl is methyl.
p and q are each 0.
R21 is heteroaryl.
Regarding Claim 46, this compound reads on a compound of formula (II) when the variables are defined as follows:
R1, R2, R4, R5, R6, R7, R11, R12, R15a, R15b, R16a, R16b, and R19 are each hydrogen.
R3a is hydroxy.
R-3b is alkyl, wherein alkyl is methyl.
R18 is alkyl, wherein alkyl is methyl.
X, Y, R21, n, and n1 are defined as noted above.
Regarding Claim 47, this compound reads on a compound of formula (III) when the variables are defined as follows:
Y is
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, wherein n1 is 1.
R3a is hydroxy.
R-3b is alkyl, wherein alkyl is methyl.
R5, R6, R15a, R15b, R16a, R16b, and R19 ae each hydrogen.
R21 is heteroaryl.
n is 1.
Taken together, Upasani teaches a method of treating tinnitus comprising administration of a compound of formula (I), formula (II), or formula (III).
Additionally, Upasani teaches the following compound at Page 180, first compound of the second to last line, as a compound of Claim 1:
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This compound reads on a compound of formula (I) as recited at instant Claim 45 when the variables are defined as follows:
X is -CR17-, wherein R17 is hydrogen.
Y is
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, wherein n1 is 1.
m is 2, and one Rx is alkyl, wherein alkyl is methyl, and the second Rx is hydroxy.
n is 1.
o is 1, and Rf is alkyl, wherein alkyl is methyl.
p and q are each 0.
R21 is heteroaryl.
Regarding Claim 46, this compound reads on a compound of formula (II) when the variables are defined as follows:
R1, R2, R4, R5, R6, R7, R11, R12, R15a, R15b, R16a, R16b, and R19 are each hydrogen.
R3a is hydroxy.
R-3b is alkyl, wherein alkyl is methyl.
R18 is alkyl, wherein alkyl is methyl.
X, Y, R21, n, and n1 are defined as noted above.
Regarding Claim 47, this compound reads on a compound of formula (III) when the variables are defined as follows:
Y is
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, wherein n1 is 1.
R3a is hydroxy.
R-3b is alkyl, wherein alkyl is methyl.
R5, R6, R15a, R15b, R16a, R16b, and R19 are each hydrogen.
R21 is heteroaryl.
n is 1.
Regarding Claim 64, this compound reads on a compound of formula (XII) when the variables are defined as follows:
Y is
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, wherein n1 is 1.
R21 is heteroaryl.
n is 1.
Taken together, Upasani teaches a method of treating tinnitus comprising administration of a compound of formula (I), formula (II), formula (III), formula (V-A), or formula (XII).
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 45-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-4 of U.S. Patent No. 11,661,437. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and patented claims are drawn to the administration of a common compound for treatment of a subject with tinnitus.
Claim 3 of U.S. Patent No. ‘437 is drawn to a method of agonizing GABAA receptor, and dependent Claim 4 specifies the subject has a CNS-related disease that is tinnitus. Claim 1 specifies the administered compound is:
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This compound reads on a compound of formula (I) as recited at instant Claim 45 when the variables are defined as follows:
X is -CR17-, wherein R17 is hydrogen.
Y is
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, wherein n1 is 1.
m is 3, and one Rx is alkyl, wherein alkyl is methyl, and the second Rx is hydroxy, and the third Rx is halogen, wherein halogen is fluorine.
n is 1.
o is 1, and Rf is alkyl, wherein alkyl is methyl.
p and q are each 0.
R21 is heteroaryl.
Regarding instant Claim 46, this compound reads on a compound of formula (II) when the variables are defined as follows:
R1, R2, R4, R5, R6, R7, R11, R12, R15a, R15b, R16a, and R16b are each hydrogen.
R3a is hydroxy.
R-3b is alkyl, wherein alkyl is methyl.
R18 is alkyl, wherein alkyl is methyl.
R19 is halogen, wherein halogen is fluoro.
X, Y, R21, n, and n1 are defined as noted above.
Regarding instant Claim 47, this compound reads on a compound of formula (III) when the variables are defined as follows:
Y is
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, wherein n1 is 1.
R3a is hydroxy.
R-3b is alkyl, wherein alkyl is methyl.
R5, R6, R15a, R15b, R16a, and R16b, are each hydrogen.
R19 is halogen, wherein halogen is fluoro.
R21 is heteroaryl.
n is 1.
Taken together, the practice of the method claimed by U.S. Patent No. ‘437 reads on the instantly claimed method recited at Claims 45-47.
Allowable Subject Matter
Claims 69-70 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 45-47, 53-54, 56, and 62-68 are rejected.
Claims 48-52, 55, 57-61, and 69-70 are objected to.
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
