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 1-13 and 16-21 are pending. Claims 7-10 and 16-21 are withdrawn. Claims 1-6 and 11-13 are rejected.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-13) and of the species
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(compound 31) in the reply filed on July 8, 2025 is acknowledged. The traversal is on the ground(s) that the standards under 35 USC §121 were applied instead of the standards under PCT Rule 13. Applicant’s arguments are persuasive. A corrected restriction requirement is set forth below.
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
WHEN CLAIMS ARE DIRECTED TO MULTIPLE CATEGORIES OF INVENTIONS
As provided in 37 CFR 1.475(b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475(c).
Restriction is required under 35 U.S.C. 121 and 372. This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1. In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claims 1-13, drawn to a compound of formula I.
Group II, claims 16-21, drawn to a method of using a compound of formula I.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I and II lack unity of invention because even though the inventions of these groups require the technical feature of formula I, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of, for example, Wang et al. WO 2020/200316 A1. Wang teaches several anticipatory compounds, including compound 9,
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. Wang 76.
Election of Species
This application contains claims directed to more than one species of the generic invention. These species are deemed to lack unity of invention because they are not so linked as to form a single general inventive concept under PCT Rule 13.1.
The species are compounds of formula I,
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. See, e.g., claim 11.
Applicant is required to elect a single species or patentably indistinct grouping of species of formula I to which the claims shall be restricted if no generic claim is finally held to be allowable. An argument that a claim is allowable or that all claims are generic is considered non-responsive unless accompanied by an election. Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which are written in dependent form or otherwise require all the limitations of an allowed generic claim.
The species lack unity of invention because even though the species require the technical feature of three specific ring systems, a pyrazolopyridine, a piperidine and a pyridine,
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this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of, for example, Wang et al. WO 2020/200316 A1. Wang teaches several compounds containing the same three ring systems, such as compound 9,
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. Wang 76.
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Advisory of Rejoinder
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Traversal
The election of an invention may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected invention or species.
Should applicant traverse on the ground that the inventions have unity of invention (37 CFR 1.475(a)), applicant must provide reasons in support thereof. Applicant may submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. Where such evidence or admission is provided by applicant, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103(a) of the other invention.
Elected Invention
Applicant's election with traverse of Group I (claims 1-13) and of the species
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(compound 31) in the reply filed on July 8, 2025 is acknowledged. Claims 1-6 and 11-13 read the elected species of the formula
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, wherein:
A is CN,
B is -O-(L1)m1-R8,
L1 is -CRfRg-, Rf and Rg are H,
m1 is 2,
R8 is 5-12-membered fused heterobicyclic ring,
X1 and X2 are N,
N is 1, and
Z is methoxy.
Examination of the elected invention was conducted in accordance with the MPEP 803.02. The elected species is allowable in view of the prior art. Examination of the Markush-type claim has been extended to the following species:
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,
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,
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and
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.These compounds represent formula (I),
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,wherein,
A is -CN,
B is -NR10R11,
R10 and R11 form a 5-6-membered heterocyclyl containing 1 N atom and 0-1 O atom(s),
X1 is CR or N, X2 is N,
R is H,
Z is unsubstituted C1-alkoxy, and
n is 0 or 1.
Since art was found on nonelected species, subject matter not embraced by the elected embodiment or the above-identified non-elected species is withdrawn from further consideration. Claims 7-10 and 14-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant is reminded that upon the cancellation of claims to a non-elected invention, the inventorship must be amended in compliance with 37 CFR 1.48(b) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. Any amendment of inventorship must be accompanied by a request under 37 CFR 1.48(b) and by the fee required under 37 CFR 1.17(i).
Priority
This application is a 371 of PCT/CN2020/135934, filed on 12/11/2020, and claims priority to CN 201911266900.X, filed on 12/11/2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/10/2022, 1/25/2024 and 7/22/2025 is in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. Each IDS has been considered by the examiner and a signed copy is enclosed herewith.
Specification
The disclosure is objected to because of the following informalities:
The specification requires “a structure of formula III” and subsequently depicts a structure labeled “IIi”. Spec. para. 149. It is unclear whether formula III has the same structure of formula IIi or has a different structure. This objection may be overcome by replacing the label “IIi” with “III” if the ambiguity was the result of an inadvertent typographical error.
Claim Objections
Claims 1, 2 and 6 are objected to because of the following informalities:
Claim 1 is objected to for being written in improper Markush format. See MPEP 2173.05(h). The Markush grouping for “B” (line 2) is missing “and” after –(L2)m2-R12.”
Claim 1 (bottom of page 2) recites “R2 and R3 together with N atom”, which is missing “a” after “with”.
Claim 1 (page 3) recites “R10 and R11 together with N atom”, which is missing “a” after “with”.
Claim 2 narrows the scope of R1, R2 and R3, inter alia, and requires that they “are each independently selected from” a Markush grouping of chemical groups; however, the claim does not specific whether R1, R2 and R3 are “substituted or unsubstituted.” Since no optional substitution was specified for R1, R2 and R3, but optional substitution was specified for R4, it would be reasonable to conclude that R1, R2 and R3 must be unsubstituted in claim 2, despite the limitation in claim 1 stating that R1, R2 and R3 may be “substituted or unsubstituted.” To improve clarity of the claim. It is suggested that claim 2 be amended to recite that “R1, R2 and R3 are unsubstituted and are each independently selected from…”
Claim 6 recites “R10 and R11 together with N atom”, which is missing “a” after “with”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(d)
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.
Claim 11 is rejected under 35 U.S.C. 112(d) 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 11 recites compound 48,
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, which falls outside the scope of claim 1 (with respect to “B”), from which claim 11 depends. Claim 1 requires a structure of formula I,
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, and provides the following definitions for B (wherein m2 is an integer from 1 to 6) and R7:
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B does not encompass halogen, which is the nature of B in compound 48. Therefore, due to compound 48, claim 11 fails to further limit claim 1.
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 1-6 and 11-13 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zhu et al. US 2023/0322769 A1 (earliest priority date: Aug. 20, 2020) as evidenced by Brayton, C. F. Cornell Vet. 1986, 76, 61-90 (pages 61-71 are attached).
Zhu teaches several anticipatory type compounds (too numerous to list) of formula (I),
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, and pharmaceutical compositions thereof further comprising a pharmaceutically acceptable carrier. Compound 66 is representative:
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. Zhu claims 1, 11 and 15. Zhu prepared a DMSO sample of the compound for testing. Zhu para. 314. This disclosure anticipates the compound of claims 1, 4, 5 and 12 with respect to formula I
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, wherein:
A is -CN (per claim 2),
B is -NR10R11 (per claim 3),
R10 and R11 form a 6-membered heterocyclyl containing 1 N atom and 1 O atom (per claim 6),
X1 is CR, X2 is N,
R is H,
Z is unsubstituted C1-alkoxy, and
n is 1.
Claim 11 depicts the compound
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, which is identical to Zhu’s compound
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.
Claim 13 requires a composition comprising the compound or salt thereof in addition to a “pharmaceutically acceptable carrier or diluent,” which embraces Zhu’s composition comprising DMSO. As evidenced by Brayton, DMSO qualifies as “pharmaceutically acceptable”.
The instant specification provides the following definition:
[0199] The "pharmaceutically acceptable carrier" means: one or more compatible solid or liquid filler or gel substances, which are suitable for human use, and which must be of sufficient purity and sufficiently low toxicity. "Compatible" as used herein means that components in a composition can be blended with the compound of this disclosure and with each other without significantly reducing the efficacy of the compound.
Brayton teaches “DMSO is considered to have low toxicity… The therapeutic intravenous (IV) dose is about 1.0 g/kg, in a 10-45% solution, administered slowly (in investigations) on humans” (citations omitted). Brayton 70. Brayton also teaches “anti-inflammatory, cryopreservative/
cryoprotective, radioprotective and antiischemic properties of DMSO when used in vivo, topically or parenterally.” Brayton 66.
Since DMSO can be used with humans, it meets the definition of “pharmaceutically acceptable.”
Claims 1-6 and 11-13 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Wang et al. WO 2020/200316 A1 (pub. Oct. 8, 2020; earliest priority date: Apr. 3, 2019) as evidenced by its English equivalent US 2022/0220104 A1, and as further evidenced by Dorokhov et al. Physiol. Rev. 2015, 95, 603-644 and Brayton, C. F. Cornell Vet. 1986, 76, 61-90 (pages 61-70 are attached).
Wang teaches several anticipatory compounds, too numerous to list, of formula (I),
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. The trifluoroacetate salts of
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and
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are representative. Wang claim 1 and p. 76 and 124-126 (‘104 para. 649-674 and 979-994), for example. Proton NMR samples of these TFA salts were prepared in deuterated methanol and diluted samples in DMSO were tested for kinase activity. ‘104 para. 159, 674, 994 and 1047. Wang also teaches the compound
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. Wang 48.
This disclosure anticipates the compounds of claims 1, 4 and 5 with respect to formula I
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, and/or their TFA salts, wherein:
A is -CN (per claim 2),
B is -NR10R11 (per claim 3),
R10 and R11 form a 5- or 6-membered heterocyclyl containing 1 N atom and 0 or 1 O atoms (per claim 6),
X1 is CR or N, X2 is N,
R is H,
Z is unsubstituted C1-alkoxy, and
n is 0 or 1.
Claim 11 depicts the compounds 66 and 70
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and
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, which are identical to Wang’s compounds
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and
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, respectively.
Claim 12 lists “acetates” as a pharmaceutically acceptable salt, which embraces the trifluoroacetate salts of Wang discussed above.
Claim 13 requires a composition comprising the compound or salt thereof in addition to a “pharmaceutically acceptable carrier or diluent,” which embraces Wang’s proton NMR samples, since deuterated methanol qualifies as “pharmaceutically acceptable” as evidenced by Dorokhov et al. (“[M]ethanol and short-lived formaldehyde are actually naturally occurring compounds in normal, healthy human individuals. There are several sources of physiological methanol in humans (FIGURE 1). Fruits, vegetables, and alcoholic beverages are likely to be the main sources of exogenous methanol in the healthy humans” (citations omitted). Dorokhov 603. “Methanol is also detected in the urine, saliva, and breast milk” (citations omitted). Dorokhov 607. In addition, the DMSO samples that Wang prepared for testing for kinase activity also qualify as pharmaceutical compositions comprising a pharmaceutically acceptable carrier or diluent, as evidenced by Brayton.
The instant specification provides the following definition:
[0199] The "pharmaceutically acceptable carrier" means: one or more compatible solid or liquid filler or gel substances, which are suitable for human use, and which must be of sufficient purity and sufficiently low toxicity. "Compatible" as used herein means that components in a composition can be blended with the compound of this disclosure and with each other without significantly reducing the efficacy of the compound.
Brayton teaches “DMSO is considered to have low toxicity… The therapeutic intravenous (IV) dose is about 1.0 g/kg, in a 10-45% solution, administered slowly (in investigations) on humans” (citations omitted). Brayton 70. Brayton also teaches “anti-inflammatory, cryopreservative/
cryoprotective, radioprotective and antiischemic properties of DMSO when used in vivo, topically or parenterally.” Brayton 66.
Since DMSO can be used with humans, it meets the definition of “pharmaceutically acceptable.
Allowable Subject Matter
The elected species,
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(compound 31), is allowable over the prior art.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA L AGUIRRE whose telephone number is (571)272-5592. The examiner can normally be reached 10 am-6 pm EDT.
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, JOSEPH K McKANE can be reached on 571-272-0699. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMANDA L. AGUIRRE/Primary Examiner, Art Unit 1626
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