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 1-24 are pending and are examined.
Information Disclosure Statement
The information disclosure statements (IDS)s submitted on 03/20/2024 were considered by the examiner.
Claim Rejections - 35 USC § 103
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.
Claims 1-24 are rejected under 35 U.S.C. 103 as being unpatentable over Michaelsen et al. (WO2015150417) in view of Killie et al. (A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn. Haematologica 93, 870-877, 2008-cited by Applicant.
The claims are drawn to a method of preventing alloimmunization with HPA-1a in a subject, wherein the subject is an HPA-1a-negative pregnant woman, or preventing fetal and neonatal alloimmune thrombocytopenia (FNAIT) caused by maternal alloimmunization with HPA-1a in a fetus of an HPA-1a-negative human subject, the method comprising parenterally administering to the subject multiple doses of a pharmaceutical composition comprising an effective amount of an anti-HPA-1a antibody, wherein the anti-HPA-1a antibody does not bind HPA-1b; wherein an initial dose of the pharmaceutical composition is administered between gestational weeks 10 and 16 of pregnancy; wherein maintenance doses of the pharmaceutical composition are administered after the initial dose, at regular dose intervals throughout pregnancy; and wherein at least one dose is administered within 72 hours post-parturition. Further limitations are that the antibody is polyclonal or a monoclonal gamma globulin, can be administered by intravenous or subcutaneous injections by appropriate means. Schedule of administration are claimed and the plasma concentration is between 6.5-8.5 ng/ml, the doses are between 5-400 µg. The dose of administration is calculated such as to achieve a Cthreshold of the anti-HPA-1a antibody of about 6-10 ng/ml. The subject is HLA-DRB3*01:01 positive.
The art is aware of the existence and the need for mitigation of the alloimmunization in an HPA-1a-negative pregnant subject, or preventing fetal and neonatal alloimmune thrombocytopenia (FNAIT) caused by maternal alloimmunization with HPA-1a in a fetus of an HPA-1a-negative subject (see for instance Kjær et al., Strategies to develop a prophylaxis for the prevention of HPA-1a immunization and fetal and neonatal alloimmune thrombocytopenia. Transfusion and Apheresis Science, 59, 102712, 2020; Ghevaert et al., Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers. Blood, 122, 313-320, 2013; Bakchoul et al., OA07, In vivo assessment of an asn-297-linked n-glycan modified HPA-1a-specific monoclonal antibody for the treatment of neonatal alloimmune thrombocytopenia. Vox Sanguinis, 99 (Suppl. 2), 12–16, 2010); Kjeldsen-Kragh et al., Risk of HPA-1a–immunization in HPA-1a–negative women after giving birth to an HPA-1a–positive child. Transfusion, 59, 1344-1352, 2019 -cited by Applicant).
The specification discloses: clearance of HPA-1a-positive platelets by polyclonal anti-HPA-1a antibodies (Example 1), the capability of polyclonal and monoclonal anti-HPA-1a antibodies to saturate HPA-1a epitopes on human and APLDQ transgenic mouse platelets (example 3). Prevention of alloimmunization by anti-HPA-1a antibodies is presented in example 5, which disclose that administration is initiated between gestational weeks 10 and 14, and is repeated weekly until parturition. A final dose is administered within about 72 hours after parturition.
Michaelsen et al. discloses the an anti-HPA-1 antibody 26.4 (the same CDR set as antibody RYLB212 instantly claimed) (p.5); the antibody is for use in preventing alloimmunization with HPA-1a in a subject (claim 20) and in a method of treating or preventing FNAIT comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of an antibody in a pharmaceutical composition (claim 26). The pharmaceutical compositions (formulations) comprising the antibody are preferably administered parenterally (by subcutaneous, intramuscular or intravenous injection by means of a syringe, optionally a pen-like syringe). The antibody is dosed in such a way to achieve a plasma concentration of 80 ng/ml (p. 31). Dosage units containing the antibodies may contain 0.1-10mg, for example 1-5mg of the active agent. Other useful doses include doses which achieve a plasma concentration of 0.1 to 1 IU/ml, for example 0.5 IU/ml (0.08 μg/ml). Such a dose of 0.5 IU/ml (0.08 μg/ml) may be achieved by intravenous administration of 2,000 IU. The antibodies may be administered to a woman who is already pregnant, preferably to a pregnant woman known to be HPA-1a negative, more preferably a woman already pregnant with an incompatible pregnancy (i.e. the mother is HPA-1a negative and the fetus is HPA-1a positive) (p. 32). The antibodies are lgG1 or lgG3 antibodies (p. 18).
The Michaelsen et al. reference is silent regarding Cthreshold of the anti-HPA-1a
antibody of about 6-10 ng/ml about the administration regimen instantly claimed and of the subject being is HLA-DRB3*01:01 positive. However, the reference indicates that the dosage units containing the antibodies may contain 0.1-10mg, for example 1-5mg of the active agent.
Kjeldsen-Kragh et al. show that in HPA-1a–negative/HLA-DRB3*01:01–positive
women, the risk of HPA-1a–immunization is 12.7% after delivery of an HPA-1a–positive
child, which is 25 times higher than in HPA-1a–negative/HLADRB3* 01:01–negative
women. Thus, the risk of HPA-1a–immunization in high-risk pregnancies is in the same
range as the risk of RhD immunization in RhD-negative women after delivery of a RhD positive child without RhD prophylaxis.
Therefore, it would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to have administered the pharmaceutical composition of Michaelsen et al. to HPA-1a–negative/HLA-DRB3*01:01–positive women and prevent alloimmunization of the pregnant subject or prevent FNAIT in a fetus with a reasonable expectation of success. This is because the patient thus chosen would have had a known high risk of alloimmunization and administration of the antibodies would have lowered this risk according to the refences cited and the knowledge in the art. The exact dosage and administration regimen would have been within the skill of a person of ordinary skill in the art since the references and the art at the time that the invention was filed offered boundaries for the artisan to consider altering by routine experimentation.
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 2 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 11, 725,063. The claims of the Patent are drawn to a method of treating fetal and neonatal alloimmune thrombocytopenia (FNAIT) in a fetus of a subject, the method comprising administering to the subject an effective amount of an anti-HPA-1a antibody (which has a CDR set shared by the antibodies of the instant Application), wherein the antibody is a full-length IgG antibody, and wherein the subject is an HPA-1a-negative woman.
While the Patent claims are not drawn to a specific administration regimen, it would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to have arrived, by routine experimentation to the instant claims with a reasonable expectation of success, This is because the claims in the U.S. Patent are drawn to an effective amount. Thus, an ordinary skilled in the art would have had to apply the knowledge in the art to find the parameters of the Effective amount.
Conclusion
No claims are allowed.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647
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