DETAILED ACTION
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 1-12, 14-22 and 31-33 have been canceled.
Claims 13 and 23-30 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group I, Claims 13 and 23-30, and of species about once every two months, and hemophilia A without inhibitors, in the reply filed on 5/7/2026 is acknowledged.
Claims 23 and 25 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and species, there being no allowable generic or linking claims.
Claims 13, 24 and 26-30 are being examined in this application, insofar as they read on the elected species of about once every two months, and hemophilia A without inhibitors.
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 of this title, 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.
Claims 13, 24, 26-27 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Negrier et al (Blood. 2017;130(Suppl_1):2366. Cited on IDS) and Machin et al (Journal of Blood Medicine. 2018;9:135-140. Cited on IDS).
The instant claims recite a method of routine prophylaxis in a patient having hemophilia A or B, comprising subcutaneously administering to the patient in need thereof 20 mg of fitusiran about once a month or about once every four weeks, or about once every two months or about once every eight weeks.
Negrier teaches a method comprising subcutaneously administering (Abstract) to patients with hemophilia A or B with and without inhibitors 50 mg of fitusiran monthly (p.2 para 1), wherein said patients ages 22-36 (p.2 para 2), and successful perioperative hemostatic management of patients in the context of antithrombin (AT) lowering with fitusiran has been observed (p.2 para 4).
Machin teaches an update of completed and ongoing clinical trials in hemophilia A and B patients, with and without inhibitors, receiving fitusiran prophylaxis for bleed prevention (p.135 Background), comprising subcutaneously administering (Abstract) to patients with hemophilia A or B without inhibitors 50 mg of fitusiran monthly (p.137 col right – para 2, Table 1).
Negrier and Machin do not teach the method wherein 20 mg of fitusiran (claims 13 and 24) is administered about once every two months (claim 24).
However, Negrier and Machin do teach the method comprises administering 50 mg of fitusiran monthly. Negrier does teach that monthly administration of fitusiran led to dose dependent AT lowering, improved thrombin generation and decreased bleeding frequency (Abstract), and Machin does teach that fitusiran provides hemostasis and annualized bleed rate lowering in hemophilia A and B patients, with and without inhibitors (p.139 col right – para 3).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to incorporate a safe dosage regimen, since Negrier and Machin both disclose that fitusiran improves thrombin generation and promotes hemostasis in patients with hemophilia A or B with and without inhibitors. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited references to incorporate a safe dosage regimen with a reasonable expectation of success.
Furthermore, in regard to claim 27, it is noted that the “wherein the administration of fitusiran to the patient is sufficient to maintain an antithrombin (AT) activity level in the patient in the range of 15% to 35%” clause does not recite any additional active method steps, but simply states a characterization or conclusion of the results of process step positively recited (e.g. analyzing). Therefore, the “wherein” clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
Claims 28-29 are rejected under 35 U.S.C. 103 as being unpatentable over Negrier et al (Blood. 2017;130(Suppl_1):2366. Cited on IDS) and Machin et al (Journal of Blood Medicine. 2018;9:135-140. Cited on IDS) as applied in claims 13, 24, 26-27 and 30 above, further in view of Usach et al (Adv Ther. 2019;36:2986-2996. Cited on IDS) and PBS (https://web.archive.org/web/20190808023552/https://www.aatbio.com/resources/buffer-preparations-and-recipes/pbs-phosphate-buffered-saline. 2019;1.).
References cited above do not teach the fitusiran is administered to the patient in a buffered solution (claim 28), and the buffered solution is phosphate buffered saline (claim 29).
However, Negrier and Machin do teach the method comprises subcutaneously administering fitusiran to patients. Before the effective filing date of the claimed invention, it was well-known in the art that buffers are added to parenteral formulations to adjust the pH with the aim of optimizing solubility and stability, as evidenced by Usach (p.2986 col right – para 1, p.2990 col right – last para). Usach teaches ideally, injectable products should be formulated as isotonic solution with a pH close to the physiological one (p.2994 col left – para 2). In addition, PBS teaches that PBS closely mimics the pH, osmolarity, and ion concentrations of the human body (p.1 para 1).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to administer fitusiran in a phosphate buffered saline, since Usach discloses that ideally injectable products should be formulated as isotonic solutions and that buffers are frequently added to parenteral formulations to optimize solubility and stability by adjusting the pH, and PBS discloses that PBS closely mimics the pH, osmolarity, and ion concentrations of the human body. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited references and routine practice to administer fitusiran in a phosphate buffered saline with a reasonable expectation of success.
Conclusion
No claims are allowed.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN Y FAN whose telephone number is (571)270-3541. The examiner can normally be reached on M-F 7am-4pm.
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/Lynn Y Fan/
Primary Examiner, Art Unit 1759
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