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 .
This application is a domestic application, filed 19 Oct 2023; and claims benefit of provisional application 63/380,357, filed 20 Oct 2022.
Claims 1-35, 39-40, 46, and 75 are pending in the current application. Claims 46 and 75, drawn to non-elected inventions, are withdrawn. Claims 1-35 and 39-40 are examined on the merits herein.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-35 and 39-40, in the reply filed on 17 June 2026 is acknowledged.
Claims 46 and 75 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 17 June 2026.
Applicant’s election of species of compound of formula (Ia) in a lyophilized formulation in the reply filed on 17 June 2026 is acknowledged.
In view of the teachings of the prior art detailed herein, search and examination has expanded to the species of compound of formula (Ia) in an aqueous formulation.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-15 and 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over Jaen et al. (WO 2019/173682 A1, published 12 Sep 2019, provided by Applicant in IDS filed 17 June 2026) in view of Baheti et al. (J. Excipients and Food Chem., 2010, 1(1), p41-54, cited in PTO-892).
Jaen et al. teaches compounds that modulate the conversion of AMP to adenosine by ecto-5'-nucleotidase (also known as CD73), and compositions comprising the same for therapeutic use (abstract). In some embodiments the CD73 inhibitor has the chemical structure
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(page 11, paragraph 26), or the elected species of compound of formula (Ia), and addressing limitations of claims 1-10. The CD73 inhibitors of the present invention may be in the form of compositions suitable for administration to a subject (page 105, paragraph 173). The pharmaceutical compositions typically comprise a therapeutically effective amount of an CD73 inhibitor contemplated by the present invention and one or more pharmaceutically and physiologically acceptable formulation agents, including excipients such as bulking agents and buffers. The buffer components can be water soluble materials such as phosphoric acid (page 106, paragraph 175), addressing limitations of claims 12-14. After a pharmaceutical composition has been formulated, it may be stored in sterile vials as a solution, suspension, gel, emulsion, solid, or dehydrated or lyophilized powder (page 106, paragraph 176), addressing limitations of claim 1. In embodiments the effective amount is at least 10 mg, between about 10 mg to about 100 mg, or least 25 mg (claims 32-34 at page 158). Effective dosage amounts and dosage regimens can readily be determined from, for example, safety and dose-escalation trials, in vivo studies (e.g., animal models), and other methods known to the skilled artisan (page 123, paragraph 247). In certain embodiments, the CD73 inhibitors contemplated for use according to the present invention may be administered at dosage levels of about 0.01 mg/kg to about 50 mg/kg, or about 1 mg/kg to about 25 mg/kg, of subject body weight per day (page 124, paragraph 251).
Jaen et al. does not specifically teach the lyophilized formulation comprising the compound and one or more amino acids (claim 1). Jaen et al. does not specifically teach the amount of the compound in the formulation (claims 18-22).
Baheti et al. teaches excipients used in various lyophilized formulations of small molecules. The role of excipients such as bulking agents, buffering agents, tonicity modifiers, antimicrobial agents, surfactants and co-solvents has been discussed. A list of ingredients used in lyophilized formulations marketed in USA has been created based on a survey of the Physician Desk Reference (PDR) and the Handbook on Injectable Drugs (page 41, abstract). Commonly used excipients used in lyophilization of small molecules include bulking agents such as sugars such as mannitol, amino acids such as arginine, glycine, and histidine, and polymers such as dextran, and solubilizing agents such as hydroxypropyl-β-cyclodextrin. Further, these excipients may serve multiple functions, such as the tonicifying agent mannitol, or the collapse temperature modifier dextran (page 46, figure 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Jaen et al. in view of Baheti et al. in order to formulate the lyophilized composition of Jaen et al. with commonly used excipients such as the amino acids taught by Baheti et al. One of ordinary skill in the art would have been motivated to combine Jaen et al. in view of Baheti et al. with a reasonable expectation of success because Jaen et al. teaches the pharmaceutical compositions comprising one or more pharmaceutically and physiologically acceptable formulation agents, including excipients such as bulking agents, and Baheti et al. teaches commonly used excipients used in lyophilization of small molecules include bulking agents such as amino acids such as arginine, glycine, and histidine, as well as bulking agents such as mannitol or dextran, and solubilizing agents such as hydroxypropyl-β-cyclodextrin. Further, regarding the claim language describing the HPBCD as a bulking agent, Baheti et al. teaches these excipients may serve multiple functions. Regarding the amount of the claimed compound present in the formulation, Jaen et al. teaches the embodiments wherein the therapeutically effective amount of the CD73 inhibitor is between about 10 mg to about 100 mg, or least 25 mg, or dosages of about 1 mg/kg to about 25 mg/kg of subject body weight, and teaches effective dosage amounts can readily be determined by methods known to the skilled artisan, suggesting it would have been routine experimentation to determine the optimal amount of the CD73 inhibitor compound in the formulation to be the therapeutically effective amount using the disclosed ranges as starting points for optimization.
Claims 16-17, 23-35 and 39-40 are rejected under 35 U.S.C. 103 as being unpatentable over Jaen et al. (WO 2019/173682 A1, published 12 Sep 2019, provided by Applicant in IDS filed 17 June 2026) in view of Baheti et al. (J. Excipients and Food Chem., 2010, 1(1), p41-54, cited in PTO-892) as applied to claims 1-15 and 18-22 above, and further in view of Niazi (Niazi, S.K., Handbook of Pharmaceutical Manufacturing Formulations, Volume 2: Uncompressed Solid Products, 2009, 2nd edition, Informa Healthcare USA, Inc., p204-227, cited in PTO-892).
Jaen et al. in view of Baheti et al. teaches as above. Jaen et al. further teaches such formulations may be stored either in a ready-to-use form, a lyophilized form requiring reconstitution prior to use, a liquid form requiring dilution prior to use, or other acceptable form (page 106, paragraph 176). Jaen et al. further teaches pharmaceutical compositions as provided herein can also be in the form of a sterile injectable aqueous or oleagenous suspensions. Acceptable diluents, solvents and dispersion media that may be employed include water or phosphate buffered saline (PBS) (page 107, paragraph 179).
Jaen et al. in view of Baheti et al. does not specifically teach the molar ratio of the compound to the one or more amino acids (claims 16-17 and 23). Jaen et al. in view of Baheti et al. does not specifically teach the amount of the excipients in the formulation (claims 24-35 and 39-40).
Niazi teaches the ordinary level of skill in the art in the field of pharmaceutical manufacturing formulations. Niazi teaches tabulated examples of approved excipients in uncompressed solid dosage forms and the quantity of the excipient used in the formulation, including sodium phosphate (bottom of page 223), mannitol (spanning pages 216-217), and glycine (bottom of page 213).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Jaen et al. in view of Baheti et al. further in view of Niazi in order to select the amount of the excipients in the formulation taught by Jaen et al. in view of Baheti et al. through routine experimentation with guidance provided by Niazi. One of ordinary skill in the art would have been motivated to combine Jaen et al. in view of Baheti et al. further in view of Niazi with a reasonable expectation of success because Jaen et al. teaches the pharmaceutical compositions typically comprise a therapeutically effective amount of the CD73 inhibitor and one or more pharmaceutically and physiologically acceptable formulation agents, including excipients such as bulking agents and buffers, Baheti et al. teaches excipients used in various lyophilized formulations of small molecules including bulking agents and buffering agents, and Niazi teaches examples of approved excipients in uncompressed solid dosage forms and the quantity of the excipient used in the formulation, suggesting it would have been routine experimentation for one of ordinary skill in the art to select the optimum or workable amount of the excipients in the formulation with guidance provided by Niazi as to the workable amounts. See also MPEP 2144.05 at II.A. providing ““[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)” In this case Jaen et al. in view of Baheti et al. teach the general conditions regarding the selection of the excipients used in the formulation, and Niazi teaches the general conditions regarding the range of amounts of the excipients used in the formulation, suggesting it would have been routine experimentation for one of ordinary skill in the art to discover the optimum or workable ranges of the amounts of the excipients. Regarding the amount of the amino acid such as arginine, Niazi provides guidance for the amount of glycine, and Baheti et al. teaches amino acids such as arginine, glycine, and histidine as equivalent bulking agents, suggesting it would have been obvious to select the amount of arginine or histidine based on the guidance Niazi teaches for the amino acid glycine. Further, regarding claim 34 reciting the pH of the aqueous formulation, Jaen et al. further teaches pharmaceutical compositions as sterile injectable aqueous suspensions such as in phosphate buffered saline (PBS), and it would have been obvious to one of ordinary skill in the art to select the pH of formulation to match the expected physiological pH of 7.4.
Conclusion
No claim is found to be allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan S Lau whose telephone number is (571)270-3531. The examiner can normally be reached Monday-Friday 9a-5p Eastern.
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/JONATHAN S LAU/ Primary Examiner, Art Unit 1693
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