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 .
DETAILED ACTION
The preliminary amendment dated 5 September 2024, in which claims 1-61 have been cancelled, and new claims 62-72 have been added, is acknowledged.
Claims 62-72 are pending in the instant application.
Claims 62-72 are being examined on their merits herein.
Priority
The instant application is a Continuation of U.S. Patent Application 16/852,225, filed on 17 April 2020, now abandoned, which is a Continuation of U.S. Patent Application 16/091,830, filed on 5 October 2018, now U.S. Patent 10,709,707, which is a National Stage entry of International Application No. PCT/US2017/026385, filed on 6 April 2017, which claims priority from U.S. Provisional Patent Application No. 62/319,648, filed on 7 April 2016.
Information Disclosure Statement
No information disclosure statement (IDS) has been submitted.
Claim objection
Claims 69, 70 are objected to because the recitation “The compound” should read –A compound (which is) --.
Claim Rejections- 35 USC 112
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 65, 67 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 65 depends on claim 64, and recites “wherein the (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate dihydrate.” This recitation renders the claim indefinite because (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate and its dihydrate are distinct chemical compounds.
Further, claim 64 recites (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate, but does not recite a hydrate of (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate. As such, there is insufficient antecedent basis for the recitation (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate dihydrate of claim 65, in claim 64.
In the interest of compact prosecution, the examiner interprets claim 64 to be drawn to a pharmaceutical solution comprising (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate or a hydrate thereof.
Claim Rejections- 35 USC 103
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 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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 62-64, 66-68, 70-72 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Akireddy et al. (US 2011/0281895, cited in PTO-892).
Akireddy (US 2011/0281895) teaches (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine [0003]
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, which is the therapeutic agent in the instant claims, or salts thereof, as a nicotinic receptor agonist [0002]. (R)-5-((E)-2-pyrrolidin-3- ylvinyl)pyrimidine provides benefits in the treatment or prevention of central nervous system (CNS) disorders and pain [0002]. Akireddy teaches salts of (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine.
Akireddy teaches ([0006]) 5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate salt, and its separation by chiral chromatography into optical isomers. Thus, Akireddy teaches (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate in optically pure form.
Akireddy teaches [0079] a pharmaceutical formulation comprising a compound of the invention and a carrier such as phosphate buffered saline, as in instant claims 63, 68, which is an aqueous liquid pharmaceutical formulation/solution, as in instant claims 66, 72.
It would have been obvious for a person of ordinary skill in the art to prepare the (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate salt and dissolve it into water or buffer to obtain an aqueous pharmaceutical formulation. The person of ordinary skill in the art would have been motivated to prepare the (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate because Akireddy teaches (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine as therapeutic agent, or salts thereof, and Akireddy teaches 5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate salt, and its separation by chiral chromatography into optical isomers. Thus, a person of ordinary skill in the art would have prepared (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate in optically pure form, with the expectation of success.
Further, dissolving said hemi-galactarate into water or buffer to prepare an aqueous solution, is routine, well within the skill of the artisan.
For these reasons, claims 62-64, 66-68, 70-72 are rejected as prima facie obvious.
Claims 64, 65, 67, 69 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Akireddy et al. (US 2011/0281895, cited in PTO-892), in view of in view of Khankari et al. (Thermochimica Acta 1995, 248, 61-79, cited in PTO-892).
Akireddy (US 2011/0281895) teaches (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine [0003]
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, which is the therapeutic agent in the instant claims, or salts thereof, as a nicotinic receptor agonist [0002]. (R)-5-((E)-2-pyrrolidin-3- ylvinyl)pyrimidine provides benefits in the treatment or prevention of central nervous system (CNS) disorders and pain [0002].
Akireddy teaches ([0006]) 5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate salt, and its separation by chiral chromatography into optical isomers. Thus, Akireddy teaches (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate in optically pure form.
Akireddy teaches [0079] a pharmaceutical formulation comprising a compound of the invention and a carrier such as phosphate buffered saline, which is an aqueous liquid pharmaceutical formulation/solution, as in instant claim 67.
Akireddy does not teach (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate dihydrate, which is the compound of instant claims 65, 69.
Khankari (Thermochimica Acta 1995, 248, 61-79) teaches crystalline stoichiometric hydrates and pharmaceutical implications of the differences in the physical properties of drug hydrates. Khankari teaches that hydration alters the pharmaceutically important properties of a drug, such as solubility, stability and bioavailability (page 64 last paragraph- page 65 first paragraph). Khankari teaches that hydrates have improved solubility compared to the anhydrate drug (Figure 3, page 66), and can affect the bioavailability (page 69) of drug molecules, as well as the stability of the corresponding formulations (pages 70-71).
Importantly, Khankari teaches that, during the development of a dosage form, it is essential to investigate whether the solid under consideration forms a hydrate(s) (pages 73-74 and Figure 9).
It would have been obvious for a person of ordinary skill in the art to synthesize the (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate salt and investigate its crystalline stoichiometric hydrates. The person of ordinary skill in the art would have been motivated to make the (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate dihydrate of the instant invention because Akireddy teaches (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate, and Khankari generally teaches investigating the crystalline stoichiometric hydrate(s) of drug molecules, as an essential step in the development of a drug dosage form. Such an optimization involving screening for pharmaceutical salts and for the corresponding crystalline stoichiometric hydrates, with the aim of optimizing drug solubility, bioavailability and stability of the formulation, is considered well within the competency of a person of ordinary skill in the art in the field of pharmaceutical process/formulation development.
Further, dissolving said hydrate into water or buffer to prepare an aqueous solution, is routine, well within the skill of the artisan.
For these reasons, claims 64, 65, 67, 69 are rejected as prima facie obvious.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 62-72 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-72 of U.S. patent 10,709,707 (cited in IDS).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the method of claims 1-72 of U.S. patent 10,709,707 renders obvious the instant claims.
Claims 1-72 of U.S. patent 10,709,707 are drawn to a method of treating dry eye disease by nasally administering (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine or a salt thereof. Claims 4, 5, 24, 25, 44, 45 recite (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate and (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate dihydrate or monhydrate.
It would have been obvious to a person of ordinary skill in the art to use the teachings of claims 1-72 of U.S. patent 10,709,707 to arrive at the instantly claimed method. Dissolving (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate or its dihydrate into water or buffer to prepare an aqueous solution, is routine, well within the skill of the artisan.
Claims 62-72 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-2 of U.S. patent 9,145,396 (cited in PTO-892), in view of Akireddy et al. (US 2011/0281895, cited in PTO-892), and Khankari et al. (Thermochimica Acta 1995, 248, 61-79, cited in PTO-892).
Claims 1-2 of U.S. patent 9,145,396 are drawn to a mono-citrate salt of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine or a pharmaceutical composition thereof.
Akireddy et al. (US 2011/0281895) teach salts of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, such as mono-citrate, or hemi-galactarate.
Khankari is as above.
It would have been obvious to a person of ordinary skill in the art to combine the teachings of claims 1-2 of U.S. patent 9,145,396 and Akireddy to arrive at the instantly claimed method.
The person of ordinary skill in the art would have been motivated to prepare another salt of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, besides the mono-citrate salt, such as hemi-galactarate, because Akireddy teaches the advantages of preparing salts of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, such as mono-citrate, or hemi-galactarate.
The person of ordinary skill in the art would have been motivated to make the (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate dihydrate because Khankari generally teaches investigating the crystalline stoichiometric hydrate(s) of drug molecules, as an essential step in the development of a drug dosage form. Dissolving (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate or its dihydrate into water or buffer to prepare an aqueous solution, is routine, well within the skill of the artisan.
Claims 62-72 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable at least over claims 1, 5, 7, 13 of U.S. patent 10,421,745 (cited in PTO-892), in view of Akireddy et al. (US 2011/0281895, cited in PTO-892), and Khankari et al. (Thermochimica Acta 1995, 248, 61-79, cited in PTO-892).
Claims 1, 5, 7, 13 of U.S. patent 10,421,745 are drawn to a mono-orotate salt or to a mono-maleate salt of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine or a pharmaceutical composition thereof.
It would have been obvious to a person of ordinary skill in the art to combine the teachings of claims 1, 5, 7, 13 of U.S. patent 10,421,745 and Akireddy and Khankari to arrive at the instantly claimed method.
The person of ordinary skill in the art would have been motivated to prepare another salt of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, besides the mono-orotate or mono-citrate salt, such as hemi-galactarate, because Akireddy teaches the advantages of preparing salts of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, such as mono-citrate, mono-orotate or hemi-galactarate. The person of ordinary skill in the art would have been motivated to make the (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate dihydrate because Khankari generally teaches investigating the crystalline stoichiometric hydrate(s) of drug molecules, as an essential step in the development of a drug dosage form. Dissolving (R)-5-((E)-2- pyrrolidin-3-ylvinyl)pyrimidine hemi-galactarate or its dihydrate into water or buffer to prepare an aqueous solution, is routine, well within the skill of the artisan.
Conclusion
Claims 62-72 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IRINA NEAGU whose telephone number is (571)270-5908. The examiner can normally be reached Mon-Fri 8-5.
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/IRINA NEAGU/Primary Examiner, Art Unit 1629
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