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 .
Priority
This application is a 371 of PCT/GB2022/051251 (05/18/2022)
and claims foreign priority to UNITED KINGDOM 2107091.7 (05/18/2021).
Claim Objections
Claim 58 includes a list but is unclear whether they are alternatives given the lack of punctuation and use of “and” or “or”. Claims 58, 61, 74 do not end with a period. Thus, these claims are objected to and require correction.
Drawings
The drawings filed 11/17/23 are objected to for not conforming to the requirements of 37 CFR 1.84(u)(1) (“View numbers must be preceded by the abbreviation “FIG.” Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation “FIG.” must not appear.”). MPEP 608.02.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the disclosure includes sequences such as SEQ ID Nos. 1-15.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 102
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.
Claims 47-50, 52-56, 73-74 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Casado et al. (WO2018234404) as evidenced by FDA (Prescribing Information for RYDAPT (MIDOSTAURIN). Webpage https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997Orig1Orig2s000lbl.pdf , 22 pages, 2017-04-28, retrieved 2026-02-04).
Casado teaches treating acute myeloid leukaemia (AML) cancer in a subject with an FLT3 mutation by administering midostaurin (claims 15, 16, 25, 50, 59; [0010]: “AML with certain activating mutations in the FLT3 gene”) where the subject has high phosphorylation at SYK: S295 and S297 as determined from a patient sample and predicted to be suitable for treatment (Claims 6, 46; Table 1, p. 59; [0043]; [0103]). Although Casado teaches that midostaurin was approved for treating AML in patients with FLT3 mutations, ([0010]: “Recently, the FLT3 inhibitor midostaurin has been approved by the FDA for treatment of adult patients having newly-diagnosed AML with certain activating mutations in the FLT3 gene.”), Casado does not specify any dosage, however, one of skill in the art reading the reference would at once envisage administering the FDA approved dosage of either 50 mg twice daily or 100 mg twice daily as evidenced by FDA (p. 1). MPEP 2131 (“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)).”). Thus, claim 47 is anticipated.
Regarding claim 48, as with 47 Casado teaches the elements of the claim, including obtaining a sample from the subject with an FLT3 mutation and determining phosphorylation to predict suitability for midostaurin treatment, and then treating the subject. Regarding the last “wherein” clause, the clause is considered a contingent limitation under the BRI is not required to be performed because the condition precedent is not met – see MPEP 2111.04 II.
Regarding claim 49, Casado teaches quantifying the phosphorylation of one or more proteins (Claims 6, 46; Table 1, p. 59; [0043]; [0103]).
Regarding claim 50, Casado teaches comparing the amount of phosphorylation ([0137]: “To investigate the biochemical differences of AML blast as a function of cell differentiation status in more detail, we compared differences in the proteomes, phosphoproteomes”).
Regarding claim 52, Casado teaches measuring phosphorylation via an in vitro assay (claim 37: “The method of treating acute myeloid leukaemia according to claim 28, wherein step (b) comprises performing an in vitro assay to detect the expression and/or activation and/or phosphorylation”).
Regarding claims 53-55, Casado teaches an ELISA assay (claim 38: “The method of claim 37, wherein said assay is an LC-MS/MS assay or an immunochemical assay such as a Western blot assay, an ELISA assay or a reversed phase protein assay”).
Regarding claim 56, Casado teaches determining phosphorylation at SYK: S295 and S297 (Claims 6, 46; Table 1, p. 59; [0043]; [0103]), corresponding to the claim “Panel B” wherein the determination is predictive of efficacy.
Regarding claim 61, Casado teaches administering midostaurin which as with claim 47 one of skill in the art would at once envisage orally 50 or 100 mg dose twice daily as FDA approved (FDA p. 1).
Regarding claim 73, Casado teaches treating acute myeloid leukaemia (AML) cancer in a subject with an FLT3 mutation by administering midostaurin (claims 15, 16, 25, 50, 59; [0010]: “AML with certain activating mutations in the FLT3 gene”).
Regarding claim 74, Casado teaches treating cancer in a subject with an FLT3 mutation by administering midostaurin (claims 15, 16, 25, 50, 59; [0010]: “AML with certain activating mutations in the FLT3 gene”) and teaches determining high level of phosphorylation at SYK: S295 and S297 (Claims 6, 46; Table 1, p. 59; [0043]; [0103]), corresponding to the claim “Panel B” which as with claim 47 and 56 anticipates the claim.
| NDA #207997 | CAPSULE;ORAL | Prescription | NOVARTIS
claim 15 midostaurin
Claim 28 -> 46 (SYK at S295 and S297; deps from 45, 41, 37, 28); [15, 16, 18, 25], 50, 59 midostaurin
FLT3 cancer ([0008]: “patients with certain mutations in FLT3”; [0010]: “FLT3 inhibitor midostaurin has been approved by the FDA for treatment of adult patients having newly-diagnosed AML with certain activating mutations in the FLT3 gene.”; [0059]-[0060]; [0070]-[0071]; [0077]; Example 8, [0146])
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.
Claims 47-61, 70-74 are rejected under 35 U.S.C. 103 as being unpatentable over Casado et al. (WO2018234404) in view of FDA (Prescribing Information for RYDAPT (MIDOSTAURIN). Webpage https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997Orig1Orig2s000lbl.pdf , 22 pages, 2017-04-28, retrieved 2026-02-04).
Casado and FDA teach as detailed in the 35 USC 102 rejection of claims 47-50, 52-56, 73-74 supra and incorporated herein. Casado in view of FDA also renders these claims obvious. "[A] disclosure that anticipates under § 102 also renders the claim invalid under § 103, for `anticipation is the epitome of obviousness.'" Connell v. Sears, Roebuck & Co., 722 F.2d 1542, 1548, 220 USPQ 193, 198 (Fed.Cir.1983) (citing In re Fracalossi, 681 F.2d 792, 215 USPQ 569 (CCPA 1982)). Furthermore, any difference among the claims and the prior art would have been well within the technical grasp of one of ordinary skill in the art such that they had a reasonable expectation of success in arriving at the claimed invention.
Regarding claim 51, Casado teaches comparing differences of phosphorylation at sites ([0134]: “[0134] We investigated differences in kinase signaling between these AML subtypes.Using a mass spectrometry method as described below we identified and quantified 9,534 phosphopeptide ions in these experiments. Of these, we selected the 150 phosphorylation sites showing the most significant differences (based on Student's t-test p-values) across groups as a phosphoproteomics signature“; [0037]-[0040]: determination of a high level of phosphorylation at sites) but does not teach the specific dividing or subtracting steps of the claim. One of ordinary skill in the art following the teaching of Casado to optimize the therapeutic effect of the FDA approved midostaurin would have considered performing simple mathematical operation such as ratios or subtraction in a comparison of the amount of phosphorylation at sites and arrive at the claimed invention with a reasonable expectation of success.
Regarding claim 57-58, Casado teaches measuring expression of proteins ([0025]) and describes “Heterogeneous nuclear ribonucleoprotein M” (Table 1, [0041]), but Casado does not specifically teach quantifying the amount of proteins present whose abundance is correlation with efficacy. One of ordinary skill in the art would have considered measuring levels of proteins known to be involved in the pathology, including heterogeneous nuclear ribonucleoprotein M, and correlate the amount with efficacy and arrive at the claimed invention with a reasonable expectation of success.
Regarding claim 59-60, Casado does not teach a combination therapy with cytarabine, however, FDA specifically teaches the combination (p. 1: Indications and Usage: “Newly diagnosed acute myeloid leukemia (AML) that is FLT3 mutation positive as detected by an FDA-approved test, in combination with standard cytarabine”) and one of ordinary skill in the art would have readily considered the combination for the same therapy and arrive at the claimed invention with a reasonable expectation of success.
Regarding claim 70-72, Casado teaches method of treatment of a cancer patient with midostaurin comprising first performing an ELISA assay on a sample from the patient ([0097]: “In methods of treatment according to this aspect of the invention”, “performing an in vitro assay to detect the expression and/or activation and/or phosphorylation”), but does not specifically teach a “kit”. One of ordinary skill in the art would have reasonably considered preparing a kit that would embody the method of treatment including first predicting whether the therapy would be efficacious (Abstract) and arrive at the claimed invention with a reasonable expectation of success.
With each of the claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success.
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 47-61, 70-74 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12282021 in view of Casado et al. (WO2018234404) in view of FDA (Prescribing Information for RYDAPT (MIDOSTAURIN). Webpage https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997Orig1Orig2s000lbl.pdf , 22 pages, 2017-04-28, retrieved 2026-02-04). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims treating AML by administering midostaurin wherein the leukemia cells have a biomarker of phosphorylation. The patent shares the same disclosure as Casado and for the same reasons in the 35 USC 103 rejection above renders the claims obvious.
Claims 47-61, 70-74 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6, 17 of copending Application No. 18702488 (reference application) in view of Casado et al. (WO2018234404) in view of FDA (Prescribing Information for RYDAPT (MIDOSTAURIN). Webpage https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997Orig1Orig2s000lbl.pdf , 22 pages, 2017-04-28, retrieved 2026-02-04). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claims treating cancer by administering midostaurin wherein the leukemia cells have a biomarker of phosphorylation. For the same reasons in the 35 USC 103 rejection over Cadado and FDA above renders the claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626