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 21-40 are pending and are examined on their merits.
Information Disclosure Statement
The Information Disclosure Statements received April 24th, 2024 (22 references), February 5th, 2026 (10 references) and March 26th, 2026 (1 reference) are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
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 21, 24, 26 and 27 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance:
Claim 21 recites a large and varied set of options associated with the R1 position of the compound of formula (I) that includes a protecting group. The position of R1 does not contain an amine group that can be protected by a BOC protecting group. The variables listed in claim 21 for the R1 group cannot simultaneously include all of the variables listed in the instant claim for the position. The only reference to BOC protection is in the applicant’s specification related to the protection of the amine group of the cystisine molecule (R1 may be a protecting group OR a 4-cysinyl). One of ordinary skill in the art cannot reasonably determine the metes and bounds of the instant claim because the variable R1 does not contain an amine group that BOC protecting groups are used for in organic synthesis, unless that variable for R1 is simultaneously more than one variable.
Claim 24 further limits claim 23 (compound of formula (I) R1 is an aryl) wherein the aryl is heteroaryl. However, the terms are not consistent with each other by the accepted definition of each in organic chemistry. An aryl is any univalent organic radical derived from an aromatic hydrocarbon by removing a hydrogen atom while a heteroaryl is both heterocyclic and aromatic; heteroaromatic.
Claim 26 further limits claim 21 wherein R1 is alkyl and the alkyl is a cycloalkyl. However, the terms are not consistent with each other by the accepted definition of each in organic chemistry. An alkyl group is an alkane missing one hydrogen while a cycloalkyl group is derived from a cycloalkane by removal of a hydrogen atom from a ring.
Claim 27 further limits claim 26 wherein the cycloalkyl is a heterocycloalkyl. However, the terms are not consistent with each other by the accepted definition of each in organic chemistry. A cycloalkyl is a type of cyclic alkyl substituent attached to a larger molecule,
consisting of a ring of carbon atoms with hydrogen atoms attached. In contrast, a
heterocycloalkyl refers to a cyclic compound that contains at least one heteroatom as part of its
ring structure. While all cycloalkyls are heterocycles, not all heterocycles are cycloalkyls, as
heterocycles can also include other types of rings with different types of atoms.
Claim Rejections - 35 USC § 102 (a)(1)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
(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 21, 22, 32, 35 and 36 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Kozikowski, et. al, Chemical Medicine: Novel 10-Substituted Cytisine Derivatives with Increased Selectivity for ᾳ4b2 Nicotinic Acetylcholine Receptors, ChemMedChem, 2007, 2, pages 1157 – 1161 (hereinafter Kozikowski).
By way of background, Kozikowski teaches that “Cytisine has been marketed in central and eastern Europe for aiding smoking cessation for more than 40 years though its effectiveness and safety have not been conclusively established through randomized, double-blind, placebo-controlled clinical trials The compound shows poor penetration of the blood-brain barrier…, yet the interesting pharmacological profile of cytisine has led to a number of medicinal chemistry efforts to create analogues with an improved subtype selectivity or PK parameters” (page 1156, column 2).
Claims 21and 22 recite the variable for the position of R1 of the compound of formula (I) that are alkyl. The has the generic structure of formula (I):
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The variables listed for R1 in both claims 21 and 22 include R1 being an alky.
Kozikowski details recent synthesis of two cytisine derivatives (5 and 6) bearing substitution at the 10-position of the pyridone ring. These two cytisine analogues showed much higher selectivity for the a4b2 nAChR subtype in binding assays than cytisine. Compound 5 includes the alkyl substitution (circled) for the variable R1 in the instant claims. For example:
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Therefore, Kozikowski anticipates the substitution of an alkyl at the R1 position of the applicant’s core structure.
Claim 33 further limits claim 21 wherein R1 is an alkoxy selected from the group
consisting of methoxy, ethoxy, propoxy, benzyloxy, and trifluoromethylbenzyloxy.
Kozikowski details recent synthesis of two cytisine derivatives (5 and 6) bearing substitution at the 10-position of the pyridone ring. These two cytisine analogues showed much higher selectivity for the a4b2 nAChR subtype in binding assays than cytisine. Compound 6 includes a methoxy group (circled) at the position of R1 of the instant claim. For example:
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Therefore, Kozikowski anticipates the substitution of a methoxy group at the R1 position of formula (I) of the applicant’s core structure.
Claim 35 further limits claim 21 wherein R2 and R3 are hydrogen.
As shown in both compound 5 and 6 of Kozikowski (above), the positions of R2 and R3 are both hydrogen.
Therefore, Kozikowski anticipates the substitution of a hydrogen at positions of R2 and R3 of formula (I) in the instant application.
Claim 36 further limits claim 21 wherein R4 is a protecting group.
As shown in both compound 5 and 6 of Kozikowski (above), the position of R4 of the applicant’s formula (I) is a Boc protecting group.
Therefore, Kozikowski anticipates the use of a Boc protecting group at the R4 position of formula (I) of the applicant’s claim.
Claim 38 further limits claim 21 wherein the compound is used in treating or preventing an addiction selected from a nicotine, alcohol, or drug addiction.
As shown in the background of the rejection of claim 21, the core compound of cytisine has been marketed in central and eastern Europe for aiding smoking cessation for more than 40 years.
Therefore, Kozikowski anticipates the use of cytisine for smoking cessation.
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 21-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,667,638 issued June 6th 2023 (hereinafter ‘628). Although the claims at issue are not identical, they are not patentably distinct from each claim 1 of ‘638 describes the same compound of the claim 21 with the exception that ‘638 identifies an enantiomerically pure compound of formula (I)
Although the claims of ‘287 describe an enantiomerically pure compound of formula (I).
The courts have ruled that an enantiomer would be obvious over the racemate unless there were secondary considerations as the person of ordinary skill in the art would look to use conventional methods to separate the enantiomers with a reasonable expectation of success. Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) The person of ordinary skill in the art would be motivated to separate the isomers in the racemate by those methods within the ordinary skill in the art to determine the more active isomer based on the Aventis Pharma Deutschland v. Lupin Ltd. decision.
The compound of formula (I) in both ‘638 and the instant application refer to the same core compound and the variables for the compound are the same in the example below:
Claim 1 ‘638 formula (I)
Claim 21 formula (I) Instant Application
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R1 is hydroxyl; halogen; alkyl
R1 is hydroxyl; halogen; alkyl
R2 is hydrogen, halogen
R2 is hydrogen, halogen
R3 is hydrogen
R3 is hydrogen
R4 is hydrogen or a protecting group
R4 is hydrogen or a protecting group
Accordingly, the claims are not patently distinct.
Claims 21-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 11,905,287 issued February 20, 2024 (hereinafter ‘287). Although the claims at issue are not identical, they are not patentably distinct from each other. The variables of both ‘287 and the instant claim 21 are the same. Even though the compounds listed in ‘287 are drawn to a method of synthesis and the compounds of the instant claims are drawn to compounds; resulting from synthesis they are not distinct from each other.
Per MPEP § 2113, "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
Claim 1 ‘287 formula (I)
Claim 21 formula (I) Instant Application
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R1 is hydroxyl; halogen; alkyl
R1 is hydroxyl; halogen; alkyl
R2 is hydrogen, halogen
R2 is hydrogen, halogen
R3 is hydrogen
R3 is hydrogen
R4 is hydrogen or a protecting group
R4 is hydrogen or a protecting group
Accordingly, the claims are not patently distinct.
Allowable Subject Matter
Claims 23, 25, 28-31, 33, 37, 39 and 40 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 21-40 are rejected.
No Claims are allowed.
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/P.R.G./ Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/ Supervisory Patent Examiner, Art Unit 1629
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