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 .
Pro Se Applicant
It appears the inventor(s) filed the current application pro se (i.e., without the benefit of representation by a registered patent practitioner). While inventors named as applicants in a patent application may prosecute the application pro se, lack of familiarity with patent examination practice and procedure may result in missed opportunities in obtaining optimal protection for the invention disclosed. The inventor(s) may wish to secure the services of a registered patent practitioner to prosecute the application, because the value of a patent is largely dependent upon skilled preparation and prosecution. The Office cannot aid in selecting a patent practitioner.
A listing of registered patent practitioners is available at https://oedci.uspto.gov/OEDCI/. Applicants may also obtain a list of registered patent practitioners located in their area by writing to Mail Stop OED, Director of the U.S. Patent and Trademark Office, P.O. Box 1450, Alexandria, VA 22313-1450.
Claim Status
There was a Notice of File Corrected Application Papers on July 9, 2025 that noted defects that the specification, abstract and claims were not consecutively numbered. Applicant re-filed the documents on September 15, 2025. On December 9, 2025, the examiner reached out to applicant regarding the pending claims. Mr. Padia indicated that claims 1-15 as set forth in applicant's submission dated September 15, 2025 were the correct set of pending claims; however, upon further review it has been determined that claims 1-26 as recited in applicant’s submission dated December 23, 2020 are the claims currently pending.
The amendment to the claims filed on December 23, 2020 does not comply with the requirements of 37 CFR 1.121(c) because the claims do not contain proper status identifiers such as (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), etc. Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c) which states:
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
(1) Claim listing. All of the claims presented in a claim listing shall be presented in ascending numerical order. Consecutive claims having the same status of “canceled” or “not entered” may be aggregated into one statement (e.g., Claims 1–5 (canceled)). The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment.
(2) When claim text with markings is required. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of “currently amended,” and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. Only claims having the status of “currently amended,” or “withdrawn” if also being amended, shall include markings. If a withdrawn claim is currently amended, its status in the claim listing may be identified as “withdrawn—currently amended.”
(3) When claim text in clean version is required. The text of all pending claims not being currently amended shall be presented in the claim listing in clean version, i.e., without any markings in the presentation of text. The presentation of a clean version of any claim having the status of “original,” “withdrawn” or “previously presented” will constitute an assertion that it has not been changed relative to the immediate prior version, except to omit markings that may have been present in the immediate prior version of the claims of the status of “withdrawn” or “previously presented.” Any claim added by amendment must be indicated with the status of “new” and presented in clean version, i.e., without any underlining.
(4) When claim text shall not be presented; canceling a claim.
(i) No claim text shall be presented for any claim in the claim listing with the status of “canceled” or “not entered.”
(ii) Cancellation of a claim shall be effected by an instruction to cancel a particular claim number. Identifying the status of a claim in the claim listing as “canceled” will constitute an instruction to cancel the claim.
(5) Reinstatement of previously canceled claim. A claim which was previously canceled may be reinstated only by adding the claim as a “new” claim with a new claim number.
Since the reply filed on December 23, 2020 appears to be bona fide, in the interest of compact prosecution, a pro se applicant, and it would not be an additional burden to the examiner, the amendment to the claims filed on December 23, 2020 will be examined. An action on the merits of claims 1-26 is contained herein.
Claim Objections
Claims 1-26 are objected to because of the following informalities: the claim or claims must commence on a separate physical sheet or electronic page. Any sheet including a claim or portion of a claim may not contain any other parts of the application or other material. See 37 CFR 1.75 (h). Appropriate correction is required.
37 CFR 1.75 Claims.
(a) The specification must conclude with a claim particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention or discovery.
(b) More than one claim may be presented provided they differ substantially from each other and are not unduly multiplied.
(c) One or more claims may be presented in dependent form, referring back to and further limiting another claim or claims in the same application. Any dependent claim which refers to more than one other claim (“multiple dependent claim”) shall refer to such other claims in the alternative only. A multiple dependent claim shall not serve as a basis for any other multiple dependent claim. For fee calculation purposes under § 1.16, a multiple dependent claim will be considered to be that number of claims to which direct reference is made therein. For fee calculation purposes also, any claim depending from a multiple dependent claim will be considered to be that number of claims to which direct reference is made in that multiple dependent claim. In addition to the other filing fees, any original application which is filed with, or is amended to include, multiple dependent claims must have paid therein the fee set forth in § 1.16(j). Claims in dependent form shall be construed to include all the limitations of the claim incorporated by reference into the dependent claim. A multiple dependent claim shall be construed to incorporate by reference all the limitations of each of the particular claims in relation to which it is being considered.
(d)
(1) The claim or claims must conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description (See § 1.58(a).)
(2) See §§ 1.141 to 1.146 as to claiming different inventions in one application.
(e) Where the nature of the case admits, as in the case of an improvement, any independent claim should contain in the following order:
(1) A preamble comprising a general description of all the elements or steps of the claimed combination which are conventional or known,
(2) A phrase such as “wherein the improvement comprises,” and
(3) Those elements, steps, and/or relationships which constitute that portion of the claimed combination which the applicant considers as the new or improved portion.
(f) If there are several claims, they shall be numbered consecutively in Arabic numerals.
(g) The least restrictive claim should be presented as claim number 1, and all dependent claims should be grouped together with the claim or claims to which they refer to the extent practicable.
(h) The claim or claims must commence on a separate physical sheet or electronic page. Any sheet including a claim or portion of a claim may not contain any other parts of the application or other material.
(i) Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation.
Claims 1-3 are objected to because of the following informalities: the amendment(s) to the claims are not clearly set forth as the text to be deleted is not clearly set forth. The objected to text is:
In claim 1,
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In claim 2,
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In claim 3,
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Appropriate correction is required.
Claims 1-3 are interpreted as the cited text being deleted in its entirety.
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 1-9, 13-14, 16, and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-17 of copending Application No. 17/836,070 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are generic to all that is recited in at least one of claims 3-17 of the reference application. That is, at least one of claims 3-17 of the reference application falls entirely within the scope of claims 1-9, 13-14, 16, and 20 or, in other words, claims 1-9, 13-14, 16, and 20 are anticipated by at least one of claims 3-17 of the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 17 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-17 and 19 of copending Application No. 17/836,070 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 19 of the reference application differs from claim 17 in that claim 19 is not limited to the use of a compound of instant Formula IA or Formula IB as instantly claimed; however, it would have been prima facie obvious to use a compound as recited in claims 3-17 of the reference application which fall entirely within the scope a compound of instant Formula IA or Formula IB as implicitly taught by claims 3-17.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 18 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-17 and 20 of copending Application No. 17/836,070 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the process of claim 20 of the reference application differs from claim 18 in that the process of claim 20 is not limited to the production of a compound of instant Formula IA or Formula IB; however, it would have been prima facie obvious to produce a compound as recited in claims 3-17 of the reference application which fall entirely within the scope a compound of instant Formula IA or Formula IB as implicitly taught by claims 3-17.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 11-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-17 of copending Application No. 17/836,070 in view of Tosh et al. J. Med. Chem. (2016), Vol. 59, pages 11006-11026 (Tosh) as applied to claims 1-9, 11-14, and 16 below.
The claims of the reference application do not explicitly recite a compound of Tables 1-14; however, it would have been obvious to substitute a compound of the reference application with a compound of Tosh based on their similar chemical structures and utilities.
This is a provisional nonstatutory double patenting rejection.
Claim 15 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-17 of copending Application No. 17/836,070 in view Jacobson et al. US 9,181,253 B2 (Jacobson) and Astrocyte Pharmaceuticals Inc. WO 2017/185061 A1 (Astrocyte) in combination as applied to claim 15 herein below.
The claims of the reference application do not explicitly recite a pharmaceutical composition further comprising an additional active agent(s); however, it would have been obvious to combine a compound of the refence application with a compound of Jacobson and/or Astrocyte based upon their common utilities for the reasons set forth herein below.
This is a provisional nonstatutory double patenting rejection.
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.
Claim 17 is 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 “use” is not a process, machine, manufacture, or composition of matter, or any new and unobvious improvement thereof.
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 1-10 and 13-26 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.
Regarding claim 1, variable R1, R3, R5, R6, R7, R9-, R10, and/or R11 read upon an improper Markush group as the last two items listed are not separated by the term “and”. When materials recited in a claim are so related as to constitute a proper Markush group, they may be recited in the conventional manner, or alternatively. For example, if "wherein R is a material selected from the group consisting of A, B, C and D" is a proper limitation, then "wherein R is A, B, C or D" shall also be considered proper. Additionally, variable R9- is not associated structurally with a compound of the claimed formula. Further, the metes and bounds of variable R10 is not clear as the variable is defined twice, each with a different scope. At least one of the cited deficiencies is not rectified in claims 2-10 and 13-18.
Regarding claim 6, variable R8- is not associated structurally with a compound of the claimed formula. Thus, it is unclear whether applicant intends for the variable to be part of the claimed invention.
Regarding claims 17-18, the claim is indefinite as the claim does not set forth an active methodological step(s).
Regarding claim 19, the general structure of “Compound A” and “Scheme K” are not set forth in the claim. Thus, one of ordinary skill in the art would not have been apprised of the metes and bounds of “Compound A” and/or the active methodological steps applicant intends to be part of the claimed invention.
Regarding claim 20, one of ordinary skill in the art would not have been apprised of the metes and bounds of a compound of Formula IA and/or Formula IB as the general structure(s) is not set forth in the claim.
Regarding claims 21-26, one of ordinary skill in the art would not have been apprised of the metes and bounds of compound A, Compound B, or compound B as the general structure(s) is not set forth in the claim.
Claim Rejections - 35 USC § 102
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.
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.
Claim(s) 1-5, 7-9, 11, 13-14, and 16 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Jacobson et al. US 9,181,253 B2 (Jacobson).
Jacobson is predicated on the concept that compounds having a ring constrained substituent or a rigid bicyclo[3.1.0]hexane ring at the 9-position which provides high potency as an antagonist and selectivity to the A3 adenosine receptor, or as a partial agonist of the A3 adenosine receptor, and at the same time lack a substituent on the 4'-position of the bicycle hexane ring (column 3, line 7 to column 4, line 56). Jacobson provides a compound of Formula I:
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or a pharmaceutically acceptable salt thereof. Specific examples of above A1 AR agonists or partial agonists include compounds of the formula (Ia):
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See columns 9-10.
Jacobson further provides a pharmaceutical composition comprising a compound as described in any of the embodiments therein and a pharmaceutically acceptable carrier (column 10, lines 10-44). The pharmaceutically acceptable carrier can be any of those conventionally used and is limited only by chemico-physical considerations, such as solubility and lack of reactivity with the compound, and by the route of administration. It will be appreciated by one of skill in the art that, in addition to the therein described pharmaceutical compositions; the compounds of Jacobson can be formulated as inclusion complexes, such as cyclodextrin inclusion complexes, or liposomes.
Jacobson also provides a method of treating a disease in an animal, e.g., a mammal, comprising administering to the animal an effective amount of a compound or a pharmaceutically acceptable salt of the invention, wherein the disease is selected from the group consisting of cancer, glaucoma, inflammatory diseases, asthma, stroke, myocardial infarction, allergic reactions, rhinitis, poison ivy induced responses, urticaria, Scleroderma, arthritis, brain arteriole diameter constriction, bronchoconstriction, and myocardial ischemia (column 12, lines 18-46).
Example 2 illustrates the ability of the compounds in accordance with an embodiment of the invention to bind to A3 adenosine receptors. The binding affinity values are set forth in Table 1. Test compounds were prepared as 5 mM stock solutions in DMSO and stored frozen.
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Example 7 illustrates the pharmacological properties of compounds illustrated in Examples 4-5. The binding affinity or % inhibition of cyclic AMP data are set forth in Table 2.
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At least compound 7b-13b, 107a-128a (FIG. 9), 101-106 (FIG. 11), 107-128 (FIG. 9), 207, 211-221, 223-234 (FIG. 13), 235A, 235B, and/or 236 is embraced by a compound of instant Formula IA, Formula IB, Formula II, Formula VII, or a compound of Tables 1-14 (e.g., compound 121; instant compound No. T13.1). Jacobson teaches a pharmaceutical composition comprising a compound of the invention (e.g., compound 7b) and a pharmaceutically acceptable diluent or carrier (e.g., DMSO). Jacobson teaches all of the instantly claimed elements. Thus, claims 1-5, 7-9, 11, 13-14, and 16 are anticipated.
Claim(s) 17-18 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Jacobson et al. US 9,181,253 B2 (Jacobson) as applied to claims 1-5, 7-9, 11, 13-14, and 16 above.
FIG. 1 depicts a reaction scheme to prepare compounds 7b-13b in accordance with an embodiment of Jacobson.
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Example 2 illustrates the ability of the compounds in accordance with an embodiment of Jacobson to bind to A3 adenosine receptors. The binding affinity values are set forth in Table 1.
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Example 8 illustrates a method of preparing compounds in accordance with an embodiment of Jacobson. Example 9 illustrates the pharmacological properties of compounds illustrated in Example 8.
Jacobson teaches all of the instantly claimed elements. Thus, claims 17-18 are anticipated.
Claim(s) 1-9, 11-14, and 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tosh et al. J. Med. Chem. (2016), Vol. 59, pages 11006-11026 (Tosh).
In the process of examining off-target interactions of nucleoside derivatives that were designed as potent ligands of the A3 adenosine receptor (AR), Tosh found that micromolar affinity was occasionally observed at 5HT2B and 5HT2C serotonin receptors (5HT2Rs) (page 11006). A prototypical A3AR agonist IB-MECA 10 (Chart 1), containing a ribose 5′-N-methyluronamide group, showed binding Ki values at 5HT2BR and 5HT2CR of 1.08 and 5.42 μM, respectively. Truncated adenosine derivatives (3, 4) also displayed significant 5HT2R affinity with Ki < 5 μM.
In the same study, Tosh reported that the substitution of the ribose tetrahydrofuryl ring of adenosine derivatives with a fused bicyclo[3.1.0]hexyl moiety (termed (N)-methanocarba), which maintained a conformation preferred by A3AR, was compatible with binding at 5HT2Rs. Thus, an otherwise A3AR-selective agonist 35, which like 10 has an N6-3-halobenzyl group, bound with even greater affinity than riboside 10 at 5HT2Rs; the Ki values of 35 at 5HT2BR and 5HT2CR were 75 and 122 nM, respectively.
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Tosh utilized some of the previously reported analogues of adenosine (Table 1, 1−13 and 35−41) that were characterized as either A1- or A3AR-selective agonists to examine the effects of structural modification on the interaction with 5HT2Rs (page 11007). The objectives were to use structural insights to synthesize novel nucleosides (14−34 and 42) with enhanced 5HT2R affinity and at the same time progressively achieve selectivity over the ARs.
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The synthesis of the (N)-methanocarba nucleoside analogues was performed as shown in Schemes 1 and 2.
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Tosh further teaches the intravenous administration of compound 23 to male Sprague Dawley rats, wherein the formulation for the IV solution contained DMSO: 20% HPBCD (10:90) (Suppl. Info., S21).
At least one of compounds 3-42 is embraced by a compound of instant Formula IA, Formula IB, Formula II, Formula IV (e.g., compound 37), Formula VII, or a compound of Tables 1-14 (e.g., compound 6; instant compound No. T14.4). Tosh teaches a pharmaceutical composition comprising compound 23 and a pharmaceutically acceptable diluent or carrier (e.g., DMSO/HPDCD). Tosh teaches all of the instantly claimed elements. Thus, claims 1-9, 11-14, and 16 are anticipated.
Claim(s) 17-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tosh et al. J. Med. Chem. (2016), Vol. 59, pages 11006-11026 (Tosh) as applied to claims 1-9, 11-14, and 16 above.
The synthesis of the (N)-methanocarba nucleoside analogues was performed as shown in Schemes 1 and 2. Tosh further teaches the intravenous administration of compound 23 to male Sprague Dawley rats, wherein the formulation for the IV solution contained DMSO: 20% HPBCD (10:90) (Suppl. Info., S21).
Tosh teaches all of the instantly claimed elements. Thus, claims 17-18 are anticipated.
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 (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.
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 for establishing a background for determining obviousness under 35 U.S.C. 103 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.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jacobson et al. US 9,181,253 B2 (Jacobson) as applied to claims 1-5, 7-9, 11, 13-14, and 16 above, and further in view of Astrocyte Pharmaceuticals Inc. WO 2017/185061 A1 (Astrocyte).
Jacobson differs from the instantly claimed invention in that Jacobson does not explicitly teach a pharmaceutical composition comprising other pharmaceutically active agent(s); however, this deficiency would have been obvious in view of the teaching of Astrocyte.
In the instant case, the references may be combined to show obviousness because Jacobson and Astrocyte are each drawn to a pharmaceutical composition comprising an agonist of an A3 adenosine receptor (A3R) useful for the treatment of a cardiovascular disease. They are from the same field of endeavor, and/or are reasonably pertinent to a pharmaceutical composition comprising a compound of Formula IA or Formula IB as defined in claim 1 or a pharmaceutically acceptable salt, ester or prodrug or metabolite thereof in a combination of other pharmaceutically active agent(s).
Astrocyte teaches a pharmaceutical composition comprising an adenosine receptor agonist analogous In structure to Formula IA (para (0013), (0156]), wherein said composition comprises a combination of other pharmaceutically active agent(s) (para [0187]).
In determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious. Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 218 USPQ 871 (Fed. Cir. 1983); Schenck v. Nortron Corp., 713 F.2d 782, 218 USPQ 698 (Fed. Cir. 1983).
It would have been obvious to one of ordinary skill in the art to combine a compound of Jacobson and Astrocyte, as both are directed to adenosine receptor agonist compounds having similar therapeutic utility toward treating stroke and cardiovascular disorders (Jacobson, col 2, In 5-12; col 12, In 34-39; Astrocyte, para [0011]). Use of materials in combination, each of which is known to function for intended purpose, is generally held to be prima facie obvious as the idea of combining them flows logically from their having been individually taught in the prior art. Thus, claims that require no more than the combination of two pharmaceutical compositions useful for treating stroke and/or cardiovascular disorders together in order to treat stroke and/or cardiovascular disorders set forth prima facie obvious subject matter.
All of the instant limitations are taught by the combination of Jacobson and Astrocyte. A person of ordinary skill in the art would have had a reason to combine the teachings of Jacobson and Astrocyte. A person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Jacobson and Astrocyte. Thus, claim 8 would have been obvious based on the preponderance of the evidence.
Claim(s) 20-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jacobson et al. US 9,181,253 B2 (Jacobson) as applied to claims 1-5, 7-9, 11, 13-14, and 16 above, and further in view of Elzein et al. US 7,381,714 (Elzein).
Jacobson differs from the instantly claimed invention in that Jacobson does not explicitly teach 1) a formulation further comprising (a) at least one release controlling polymer selected from the group consisting of pH-dependent polymers and non-pH-dependent polymers, and (b) at least one stabilizer selected from the group consisting of acidifying agents and hydrophobizing agents or 2) a formulation in an enteric-coated capsules further comprising at least one stabilizer selected from the group consisting of acidifying agents and hydrophobizing agents; however, these deficiencies would have been obvious in view of the teachings of Elzein.
In the instant case, the references may be combined to show obviousness because Jacobson and Elzein are each drawn to a pharmaceutical composition comprising an agonist of an A3 adenosine receptor (A3R). They are from the same field of endeavor, and/or are reasonably pertinent to a pharmaceutical composition comprising a compound of Formula IA or Formula IB, Compound A or Compound B, or a pharmaceutically acceptable salt, ester or prodrug or metabolite thereof in a combination with (a) at least one release controlling polymer selected from the group consisting of pH-dependent polymers and non-pH-dependent polymers, and (b) at least one stabilizer selected from the group consisting of acidifying agents and hydrophobizing agents.
It is an object of Elzein to provide a method of treating a disease or condition that can be treated with partial or full selective A adenosine receptor agonists using a compound having the structure of Formula I:
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.
See column 3, lines 4-65. Diseases that can be treated using the method of Elzein include, but are not limited to, atrial fibrillation, atrial flutter, congestive heart failure, epilepsy, stroke, diabetes, obesity, ischemia, stable angina, unstable angina and myocardial infarction.
The compositions of Elzein can be formulated so as to provide quick, sustained or delayed release of the active ingredient after administration to the patient by employing procedures known in the art (column 24, lines 38-58). Controlled release drug delivery systems for oral administration include osmotic pump systems and dissolutional systems containing polymer coated reservoirs or drug-polymer matrix formulations. Elzein teaches that tablets or pills may be coated or otherwise compounded to provide a dosage form affording the advantage of prolonged action, or to protect from the acid conditions of the stomach (column 25, lines 29-43). For example, the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former. The two components can be separated by an enteric layer that serves to resist disintegration in the stomach and permit the inner component to pass intact into the duodenum or to be delayed in release. A variety of materials can be used for such enteric layers or coatings, such materials including a number of polymeric acids and mixtures of polymeric acids with such materials as shellac, cetyl alcohol, and cellulose acetate.
Elzein discloses a sustained release formulation in Example 28.
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HPMC is a release controlling polymer; methacrylic acid copolymer is a hydrophobizing agent. Elzein teaches that the resulting tablets may be coated with an optional film-forming agent, for identification, taste-masking purposes and to improve ease of swallowing.
In determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious. Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 218 USPQ 871 (Fed. Cir. 1983); Schenck v. Nortron Corp., 713 F.2d 782, 218 USPQ 698 (Fed. Cir. 1983).
It would have been obvious to one of ordinary skill in the art to provide a compound of Jacobson in a coated sustained release of Elzein. The compounds of Jacobson and Elzein have close chemical structures (e.g., adenosine derivatives), share a common function (e.g., adenosine receptor agonists), and have a common utility of treating cardiovascular disorders. One would have been motivated to do so in order to afford the advantage of prolonged action, to protect from the acid conditions of the stomach, and/or for taste-masking purposes and to improve ease of swallowing. One would have had a reasonable expectation of success as Elzein teaches coated sustained release formulations containing an active agent with a close chemical structure and/or function.
All of the instant limitations are taught by the combination of Jacobson and Elzein. A person of ordinary skill in the art would have had a reason to combine the teachings of Jacobson and Elzein. A person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Jacobson and Elzein. Thus, claims 20-26 would have been obvious based on the preponderance of the evidence.
Conclusion
Claims 1-26 are pending. Claims 1-26 are rejected. No claims are allowed.
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/PATRICK T LEWIS/Primary Examiner, Art Unit 1691
/PL/