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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/26/2025 has been entered.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/23/2025, 08/07/2025 and 01/20/2026 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restrictions
Applicant's election with traverse of Group I, claims 27-31 and 35-36 in the reply filed on 01/20/2026 is acknowledged. While applicant’s arguments are not persuasive – see response to arguments below – the restriction requirement is nevertheless withdrawn in view of the overlapping scope of the claims.
Response to Arguments
Applicant’s arguments, see pp. 5-6, filed 02/26/2025, with respect to the rejection of claims 27-34 under 35 U.S.C. 102((a)(1)/(a)(2)) have been fully considered and are persuasive. Amendments moot the rejection. Particularly, the administration of tacrolimus overcomes the anticipation rejection. The rejection of 08/27/2024 has been withdrawn.
Applicant's arguments filed 02/26/2025 with respect to the obviousness rejection have been fully considered but they are not persuasive.
The Examiner disagrees with applicant’s arguments regarding claim interpretation with respect to intended use. It is acknowledged that the claims are directed toward methods of treating hematological malignancies and/or treating a patient at risk of recurrence of hematological malignancy. However, in Jansen v. Rexall Sundown, Inc., 342 F.3d 1329, 1333-34, 68 USPQ2d 1154, 1158 (Fed. Cir. 2003), a claim directed to a method of treating or preventing pernicious anemia in humans by administering a certain vitamin preparation to "a human in need thereof," the court held that the preamble is not merely a statement of effect that may or may not be desired or appreciated, but rather is a statement of the intentional purpose for which the method must be performed. Thus the claim is properly interpreted to mean that the vitamin preparation must be administered to a human with a recognized need to treat or prevent pernicious anemia. See MPEP 2111.02.
In the instant claims, the purpose can be construed as limiting the treated population to those in need treatment of hematological malignancies and/or treating a patient at risk of recurrence of hematological malignancy. The statement of purpose/”in need thereof” are given weight in the interpretation of the instant claims in that they limit the population treated. However, with respect to the prior art rejection, this “difference” in purpose does not differentiate the treated patient populations between the instant claims and prior art. The prior art treatment may be explicitly drawn to GvHD. However, it is clear that the GvHD arises as a component of treatment of hematological malignancies and/or treating a patient at risk of recurrence of hematological malignancy. Therefore, the patient population is those in need treatment of hematological malignancies and/or treating a patient at risk of recurrence of hematological malignancy. In other words, the patient populations are identical and accordingly the statement of purpose is not construed to limit the patient population in a way which differentiates the claims from the prior art with respect to the patient population.
With respect to allegations of unexpected results, the claims are drawn to combinations comprising tacrolimus. The data provided does not appear to show unexpected results commensurate in scope with the claims. See particularly Table 6 where the administration with Tacrolimus does not show a significant improvement in recurrence and survival rate.
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.
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 27-31 and 35-45 are rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0000811 A1 in view of Bauters et al., "Practical considerations in the use of intravenous tacrolimus in hematopoietic stem cell transplantation patients" J Oncol Pharm Practice 2015, Vol. 21(6) 478–480.
‘811 teaches a method of administering 2-amino-2-[4-(3-benzyloxyphenylthio-2-chlorophenyl]ethyl-propane-1,3-diol (hereinafter “KRP-203”) (“Patients will be assigned the following treatment: Single arm: [KRP-203], 3 mg once daily for 111 days”, Para. [0046]) to patients who have undergone hematopoietic stem cell transplantation for the treatment of hematological malignancies (“2. Patients must have a hematological malignancy”, Para. [0042]; “B. Drug treatment period from Day 1 to Day 111 … D. Transplanation … will be performed on Day 11.” [Para. [0044]). Note that patients qualify as “patients who have undergone hematopoietic stem cell transplantation for the treatment of hematological malignancies” following Day 11 in the prior art, and the drug is administered from Day 1 to Day 111. ‘811 also teaches a patient population wherein “the patient has previously undergone
myeloablation and subsequent hematopoietic stem cell transplantation” of instant claims 27 and 37 (“C. Myeloablative conditioning will be performed between Day 2 and Day 10 as per standard of care using chemotherapy … D. Transplanation … will be performed on Day 11.” Para. [0044]). Note that the patient qualifies as “a patient [who] has previously undergone myeloablation and subsequent hematopoietic stem cell transplantation” following Day 11 in the prior art, and the drug is administered from Day 1 to Day 111. Because the drug is administered to the same population, the treatment of hematological malignancies of claims 27 and the treating a patient at risk of recurrence of hematological malignancy 37 is inherent in the method taught by ‘811. Furthermore, It is clear that while the prior art is directed to treating/preventing GVHD, the treatment/prevention of GVHD is necessitated by the treatment of hematological malignancies. The skilled artisan recognizes that the method taught by ‘811 is merely a component of a treatment plan which includes the treatment of hematological malignancies of claims 27 and 37.
‘811 does not teach combination therapy with tacrolimus and/or methotrexate.
Bauters et al. teaches a combination of a calcineurin inhibitor (cyclosporine or tacrolimus) in conjunction with a short course methotrexate as prophylaxis of GvHD. ‘811 teaches the administration of KRP-203 at the claimed dosage of 3 mg / day “Patients will be assigned the following treatment: Single arm: [KRP-203], 3 mg once daily for 111 days”, Para. [0046]) with methotrexate and cyclosporin A (“Usually, a compound of formula (I) will be given as an add-on treatment to the normal treatment drug given to patients to prevent GVHD”, Para. [0064]; “patients may receive prophylaxis as per institutional practices using for example cyclosporin A (CsA), mycophenolate or methotrexate. As an example, patients begin CsA on Day 8 … monitored at least weekly”, Para. [0065]; “Methotrexate schedule and dosing may be adapted according to internal standards of an institution (e.g. 10 mg/kg on Day 11, 6 mg/kg on Day 13 and on Day 16)” Para. [0066]). Note that while ‘811 does not expressly teach the combination of methotrexate and cyclosporin A with KRP-203, the combination would have been at once envisaged by the skilled artisan upon consultation with Para. [0064-0066] of ‘811. See also “D. … Standard activities, in addition to the investigative treatment may include standard GVHD prophylaxis” (Para. [0045]) and NEUMANN which teaches “The combination of Cyclosporin A (CSA) and Methotrexate (MTX) is considered to be the standard regimen for the prevention of graft-versus-host disease (GVHD) after stem cell transplantation (SCT)” (Abstract)). A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962)). In this case, the skilled artisan would have at once envisaged the combination of CsA and MTX despite being the two taught separately or in the alternative in ‘811, as the combination is considered “standard GVHD prophylaxis.” An explicit combination of the components is not necessary to make the disclosure anticipatory as the skilled artisan would ‘at once envisage’ the combination of the two components. With respect to the combination comprising tacrolimus, a PHOSITA would have found it obvious to substitute the CsA taught by ‘811 with tacrolimus which is taught by Bauters et al. to be an alternative to cyclosporine. Accordingly, KRP-203 combination therapy with tacrolimus and/or methotrexate is prima facie obvious. The enabled suppression recited in claims 27, 37 and 44-45 necessarily flows from the teachings of the prior art. Accordingly, claims 27-31 and 35-45 are obvious.
Conclusion
Claims 27-31 and 35-45 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JED A KUCHARCZK whose telephone number is (571)270-5206. The examiner can normally be reached Mon-Fri 7:30 to 5.
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/JED A KUCHARCZK/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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