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 .
Claim Interpretation
Regarding the clause(s) “wherein administering the effective amount…increases survival and/or leukemia-free…about 28, 30, 32, or 34 months”, “wherein administering the effective amount… increases survival and/or leukemia-free…by providing best supportive care alone”, and/or “wherein administering the effective amount… increases survival and/or leukemia-free…and/or provides the subject with…with a bi-allelic TP53 mutation”, claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. A “wherein” clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited. See MPEP 2111.04. In the instant case, the clause(s) simply expresses the intended result of a process step positively recited (e.g., administering to the subject an effective amount of cedazuridine and an effective amount of decitabine).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 88-89 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 88-89, the parenthetical phrase(s) “(e.g., 1, 2…or 5)”, “(e.g., 100 mg)”, and/or “(e.g., 35 mg)” render(s) the claim indefinite because it is unclear whether the limitations within the parentheses are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1-2, 4-5, 7, 16, 19, 23, 25, 34, 37, 41, 43, and 52 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Garcia-Manero, Guillermo, et al. "A phase 2 dose-confirmation study of oral ASTX727, a combination of oral decitabine with a cytidine deaminase inhibitor (CDAi) cedazuridine (E7727), in subjects with myelodysplastic syndromes (MDS)." Blood 130 (2017): 4274 (Garcia-Manero).
Garcia-Manero discloses that the authors reported results of a Phase 1 dose escalation study showing that the combination of oral cedazuridine (CED), a CDAi, at 100 mg/d and oral DAC at 30 and 40 mg/d achieved 5-day decitabine AUC levels that were 85 and 144% respectively of the 5-day AUC of DAC at 20 mg/m2 administered as a one hour intravenous infusion dailyx5 (IV-DAC) (Abstract, Aims). (Garcia-Manero. Blood 2016 128:114). Garcia-Manero report here the results of a phase 2 pharmacokinetic (PK) study designed to confirm that the fixed dose combination of oral DAC (35 mg/d) and CED (100 mg/d) (ASTX727) is comparable to IV-DAC in term of DAC AUC exposure. Garcia-Manero teaches that adult patients with intermediate (Int) or high risk (HR) MDS or Chronic Myelomonocytic Leukemia (CMML) were enrolled in a cross-over Phase 2 study (Abstract, Methods). Patients were randomized 1:1 to receive in the first 28 day cycle, either 5 days of IV-DAC or 5 days of ASTX727, followed by a cross-over to the other in Cycle 2. Cycles 3 forward were with ASTX727. Garcia-Manero teaches that the median age of the patients was 69.7 yr (range 32-87) (Abstract, Results). The MDS-IPSS status of the patients was Int-1 in 20 (40%), Int-2 in 13 (26%) and HR in 8 (16%); 9 (18%) had CMML. The DAC AUC results from both IV-DAC and ASTX727 are presented in Table 1. Garcia-Manero teaches that clinical benefit was observed in 31 (62%) patients, with 8 (16%) CR, 14 (28%) mCR, and 9 (18%) HI.
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Thus, Garcia-Manero teaches the administration of ASTX727 (e.g., a combination of oral decitabine (35 mg) and cedazuridine (100 mg)) to an instant subject in need thereof. Thus, claims 1-2, 4-5, 7, 16, 19, 23, 25, 34, 37, 41, 43, and 52 are anticipated.
Claim(s) 88-89 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Garcia-Manero, Guillermo, et al. "A phase 2 dose-confirmation study of oral ASTX727, a combination of oral decitabine with a cytidine deaminase inhibitor (CDAi) cedazuridine (E7727), in subjects with myelodysplastic syndromes (MDS)." Blood 130 (2017): 4274 (Garcia-Manero) as applied to claims 1-2, 4-5, 7, 16, 19, 23, 25, 34, 37, 41, 43, and 52 above.
Garcia-Manero discloses ASTX727 (e.g., a combination of oral decitabine (35 mg) and cedazuridine (100 mg)). Thus, claims 88-89 are anticipated.
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.
Claim(s) 55, 59, 61, and 70 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garcia-Manero, Guillermo, et al. "A phase 2 dose-confirmation study of oral ASTX727, a combination of oral decitabine with a cytidine deaminase inhibitor (CDAi) cedazuridine (E7727), in subjects with myelodysplastic syndromes (MDS)." Blood 130 (2017): 4274 (Garcia-Manero) as applied to claims 1-2, 4-5, 7, 16, 19, 23, 25, 34, 37, 41, 43, and 52 above, and further in view of Chang, Chun‐Kang, et al. "TP53 mutations predict decitabine‐induced complete responses in patients with myelodysplastic syndromes." British Journal of Haematology 176.4 (2017): 600-608 (Chang).
Garcia-Manero differs from the instantly claimed invention in that Garcia-Manero does not explicitly teach a method wherein the subject has a TP53 mutation; however, this deficiency would have been obvious in view of the teachings of Chang.
In the instant case, the references may be combined to show obviousness because Garcia-Manero and Chang are each drawn to a composition comprising decitabine useful for the treatment of patients with myelodysplastic syndromes. They are from the same field of endeavor, and/or are reasonably pertinent to a method of treating MDS or CMML in a subject having a TP53 mutation.
Chang teaches, to identify the molecular signatures that predict responses to decitabine (DAC), they examined baseline gene mutations (28 target genes) in 109 myelodysplastic syndrome (MDS) patients at diagnosis. Chang determined that TP53 mutations predicted complete response (CR), as 10 of 15 patients (66.7%) who possessed TP53 mutations achieved a CR. Chang teaches that TP53 mutations might predict decitabine-induced complete responses in patients with MDS. Chang teaches that DAC-induced responses may result from partial suppression of malignant clones containing mutated TP53 genes.
In determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious. Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 218 USPQ 871 (Fed. Cir. 1983); Schenck v. Nortron Corp., 713 F.2d 782, 218 USPQ 698 (Fed. Cir. 1983).
It would have been obvious employ a method of Garcia-Manero to treat a subject having a TP53 mutation as Chang teaches that TP53 mutations predicted complete response (CR) in MDS patients. One would have had a reasonable expectation of success as Chang teaches that 66.7% of MDS patients who possessed TP53 mutations achieved a CR.
All of the instant limitations are taught by the combination of Garcia-Manero and Chang. A person of ordinary skill in the art would have had a reason to combine the teachings of Garcia-Manero and Chang. A person of ordinary skill in the art would have had a reasonable expectation of success in combining the teachings of Garcia-Manero and Chang. Thus, claims 55, 59, 61, and 70 would have been obvious based on the preponderance of the evidence.
Conclusion
Claims 1-2, 4-5, 7, 16, 19, 23, 25, 34, 37, 41, 43, 52, 55, 59, 61, 70, and 88-89 are pending. Claims 1-2, 4-5, 7, 16, 19, 23, 25, 34, 37, 41, 43, 52, 55, 59, 61, 70, and 88-89 are rejected. No claims are allowed.
Contacts
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PATRICK T LEWIS whose telephone number is (571)272-0655. The examiner can normally be reached Monday to Friday, 10 AM to 4 PM EST (Maxi Flex).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PATRICK T LEWIS/Primary Examiner, Art Unit 1691
/PL/
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