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 .
Priority
The present Application, filed January 2, 2024, is a national stage entry under 35 U.S.C. § 371 of International Patent Application No. PCT/CN2023/105594, filed July 3, 2023, which claims priority to Chinese Patent Application Nos. CN2022111682687and CN2022107755647, filed September 23, 2022 and July 1, 2022, respectively.
Status of the Claims
In the amendment filed June 22, 2023, claims 11-13 are amended. Claims 1-14 are currently pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June March 6, 2024 is acknowledged.
Claim Objections
An objection is raised to claim 1:
Claim 1 is objected to because of the following informalities: the claim refers four times to a “cyan” group, e.g. in the description of alternatives for R8, R3, R4/R5, and in the generic definition of substituents. This is not a recognized chemical term and is assumed to refer to a “cyano” group. Appropriate correction is required.
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 13-14 are rejected under 35 U.S.C. § 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because they are directed toward “a use” of the compound of claim 1. "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, (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 § 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.
Claims 1-5, 10, and 12-14 are indefinite:
Claims 1-5, 10, and 12-14 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 1 is indefinite for reciting the parenthetical expressions that the alternative fused bicyclic heterocyclyl group or fused bicyclic heteroaryl group of Ring A is “preferably five-membered fused six-membered ring,” and for using similar “preferably” language in the description of R2. Such exemplary or preferential language is ambiguous and renders it unclear whether this is intended to limit the scope of the claim or instead states a mere preference that is not intended to limit the scope of the claim in any way. Similarly, claim 5 is indefinite for reciting five instances of “preferably” in the description of ring D and of ring A.
Claim 1 is further indefinite for reciting, “R2 is selected from the group consisting of: R7, and -L2R7…wherein, R7 is selected from the group consisting of: hydrogen, none…,” because a person of ordinary skill in the art could not reasonably determine the metes and bounds of this limitation. In particular, it would be unclear what “none” means in this context. For example, where R2 is R7, R7 is directly bonded to an amino nitrogen. If R7 is “none” (or nothing), it is unclear whether this refers to some sort of radical, or the amine is an imine, or something else. Claims 2-4, 10, and 12-14 are indefinite for depending from claim 1 without curing this point of indefiniteness.
Claim 10 is indefinite for reciting that Ra has a structure according to the formulae
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while the substituent R9 is undefined in either claim 10 or its base claim 1. Due to this omission, one could not reasonably determine the metes and bounds of this claim. For the purpose of examination against the prior art, claim 10 will be construed by applying the definition of R9 recited in claim 3.
Claim 13 is further indefinite for the reciting a “use” of the compound of claim 1 in the preparation of drugs, implying that the claim relates to drug preparation (i.e. a method of drug preparation). However, no method steps are recited, leaving uncertainty as to what is claimed. The claim recites details of diseases that may be treated by the drugs that are prepared by the “use” but the connection of these details to the claimed subject matter is likewise unclear, because the claimed subject matter is unclear. Claim 14 is likewise further indefinite for depending from claim 13 and reciting the same “use.”
Claim 13 is further indefinite for reciting diseases “associated with abnormal gene levels or abnormal expression of PRMT5” because a person of ordinary skill in the art could not reasonably determine the metes and bounds of this limitation. In particular, it would be unclear what it means for a disease to be “associated with” abnormal gene levels or abnormal expression. For example, it might be diseases that are generally known to be coincident with such genetic or protein expression abnormalities, a disease which is known to be coincident in a specific patient with such abnormalities, a disease for which a theoretical mechanistic connection or explanation exists relative to such abnormalities, or something else. It would also be unclear, despite the parenthetical “such as” expression, what constitutes abnormal gene levels. For example, this could refer strictly to increases in copy number and deletions, it could refer to abnormalities in transcript levels, or something else. It is assumed that altered levels of protein expression, or mutations in the protein, fall under the umbrella of “abnormal expression of PRMT5.”
Claim 13 is further indefinite for reciting the parenthetical expression, “(such as corresponding nucleic acid mutations, deletions, or abnormal MTAP gene level, or the methyltransferase is ectopic or fused or overexpressed).” This is similar to the rejection of claims 1 and 5 for recitations of “preferably.” In this case, the exemplary language “such as” renders it unclear whether the subsequent listing is intended to limit the scope of the claim in any way or is purely exemplary with no intended limitation. Claim 14 is further indefinite for reciting, “the disease or disorder,” which has no antecedent basis.
With respect to the indefinite “use” claims 13 and 14, for the purpose of examination against the prior art, they will be construed as being directed to “drugs” or pharmaceutical compositions, comprising a compound of claim 1 in combination with at least one excipient, where the drug is intended for treatment of the recited disease types.
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.
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.
Claims 6, 8, and 11 fail to incorporate the limitations of their base claim:
Claims 6, 8, and 11 are 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.
Claims 6, depending from claim 1, recites “wherein, R2 is selected from the group consisting of: R7, and -L2R7; wherein, L2 is selected from the group consisting of: -O-, -CHR-, carbonyl, S, and -NH-….” However, claim 1 recites that “L2 is selected from the group consisting of: -O-, -CHR-, -C(R)R-, and carbonyl.” Claim 7 thus adds alternative moieties for L2 (S and −NH−) that are not available in the base claim 1, and therefore does not include all limitations of its base claim.
Claim 11 recites a compound of claim 1 selected from among 317 species. However, compounds 108 and 114 are not compounds of claim 1, at least because neither has the required Ra fused ring system connected to the carbonyl (or thiocarbonyl) as required in the generic formula of claim 1. Because claim 11 recites compounds that are outside the scope of claim 1, claim 11 does not include all the limitations of the claim from which it depends. 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.
Claims 1-4, 6-8, 10, and 12 are anticipated by Amegadzie:
Claims 1-4, 6-8, 10, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by International Patent Application Publication No. WO2022115377 to Amegadzie (hereinafter, “Amegadzie”).
Claim 1 recites a compound of formula I
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where the variable moieties are as defined. Ra can be various fused bicyclic or tricyclic structures; R2 can be a variety of moieties ranging from hydrogen to fused ring cycles and spirocyclics, with an optional linker; L1 is one of several relatively simple linkers; ring A is a fused bicyclic heterocyclyl or heteroaryl; and R8 can be a variety of structures ranging from hydrogen to a linked ring structure. Exemplary compounds include those from claim 11, such as compound No. 1
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Amegadzie teaches compounds useful for inhibiting PRMT5 activity that may have use in treating proliferative disorders (Abstract), and are structurally characterized by a Formula (I)
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.
where the variable moieties are as defined (paragraph [005]). Multiple working examples of Amegadzie are species of instant claim 1, such as 4-amino-N-(3,4-dihydro-2H-pyrano[2,3-c]pyridin-6-ylmethyl)-N-((1R)-1-(2-pyrimidinyl)ethyl)-1,3- dihydrofuro[3,4-c]quinoline-8-carboxamide (Ex. 469)
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Example 469 of Amegadzie is a compound of instant claim 1 where Ra is
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with X1 and X2 being CH, R3 is H, R4 is OH-substituted methyl, R5 is methyl, and R4 and R5 together form a 5-membered ring (dihydrofuran); W is O; R2 is –L2R7 where L2 is -CHR- where R is methyl and R7 is pyrimidinyl (unsubstituted 6-membered heteroaromatic ring1); L1 is methyl; ring A is 3,4-dihydropyranopyridine (a 12-membered fused bicyclic heterocycle); and R8 is H. Because Example 469 of Amegadzie is a compound of instant claim 1, claim 1 is anticipated.
With respect to claim 2, instant ring A of Example 469 of Amegadzie is 3,4-dihydropyranopyridine, and corresponds to the ring A option in the middle of the second to last row of claim 2. With respect to claim 3, instant Ra of Example 469 of Amegadzie corresponds to the second structure in the second to last row of alternatives, where R9 is hydrogen (or m is zero) and X1, X2, and R3 are as defined above. With respect to claim 4, instant ring A of Example 469 of Amegadzie is 3,4-dihydropyranopyridine, and corresponds to the ring A option in the middle of the second to last row of claim 4, where ring C is 3,4-dihydropyran (6-membered, partially unsaturated heterocycle).
With respect to claims 6-8, instant R2 of Example 469 of Amegadzie is –L2R7 where L2 is -CHR- where R is methyl and R7 is pyrimidinyl (unsubstituted 6-membered heteroaromatic ring). With respect to claim 10, Ra of Example 469 of Amegadzie is
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where R9 is H and X1 and X2 are CH.
With respect to claims 12-14, Amegadzie teaches pharmaceutical compositions comprising compounds of the invention (e.g. Example 469) and at least one pharmaceutically acceptable excipient (paragraph [023]). With further respect to claim 13-14, Amegadzie teaches that the disclosed compounds, and therefore the compositions (drugs) are useful for the treatment of cancer such as ovarian, lung, lymphoid, glioblastoma, colon, melanoma, gastric, pancreatic or bladder cancer (paragraph [024].
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 1-12 are provisionally rejected for nonstatutory double patenting over the ’491 application:
Claims 1-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18/877,491 to Wang et al. (hereinafter, “the ’491 application”). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ’491 application overlap broadly in scope with the instant claims. The ’491 application corresponds to U.S. Patent Application Publication No. 2025/0376473 which is listed in the attached form 892.
Claim 1 of the ’491 application is directed to a compound formula I or formula II, where formula I of the ’491 application is essentially the same as instant formula I (same core structure, with substantially identical variable definitions). The sub-genus of reference claim 6 broadly overlaps with the sub-genera of instant claims 2 and 4; reference claim 2 overlaps broadly with instant claim 3; defines a broadly similar sub-genus to that of instant claim 3, reference claim 5 overlaps instant claim 5; reference claim 4 overlaps broadly with instant claim 6; reference claim 7 overlaps broadly with instant claims 7-8; reference claim 10 overlaps broadly with instant claim 9. Reference claim 11 recites 425 individual species, which provide examples of compounds that match the sub-genera of instant claim 10 and of the other dependent claims; furthermore some species of reference claim 11 are identical to species of instant claim 11. For instance, example No. 281 of reference claim 11 is identical to example No. 279 of instant claim 11. Reference claim 13 recites a pharmaceutical composition that broadly overlaps with that of instant claim 12. Thus, the subject matter of instant claims uniformly represents an obvious variation of the subject matter of reference claims 1-13, and vice-versa. It is noted that if instant claims 13-14 were drafted as methods of treatment, they would potentially overlap with reference claims 16-18.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER K SHOWALTER whose telephone number is (571)270-0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm, eastern time.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached on (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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/ALEXANDER K. SHOWALTER/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 While it would otherwise potentially be ambiguous whether “fused bicyclic heterocycle” includes systems in which one of the rings is aromatic, the examples and instant claim 4 make clear by inference that it does.
Prosecution Insights