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 .
This application is identified as a divisional of US application 17/173,677, filed 02/11/2021 (now US Patent No. 11,746,386), which is a continuation of US application no. 15/774, 978, filed 05/09/2018 (now US Patent No. 10,927,418), which is the national stage of PCT/US16/61444, filed 11/10/2016, claiming priority to US provisional application 62/254,109, filed 11/11/2015.
Application Status
While it is noted that the instant application is directed to subject matter non-elected in “grandparent” application 15/774,978, as this application is not a divisional of application 17/173,677 (in which no restriction requirement was issued), the status of the instant application should be corrected to identify it as a continuation (rather than a divisional) of the ‘677 application.
Information Disclosure Statement
The information disclosure statement filed 16 August 2024 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. In particular, only the reference for which an English language equivalent was provided (cite B2) has been considered.
The information disclosure statement filed 12 May 2023 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. In particular, cite no B1 has not been considered.
Drawings
The drawings are objected to because Figures 1A and 2A-2C include blurry text. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112(b)/second paragraph/Claim Interpretation
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 1-17 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.
Claims 1-11 are indefinite over the recitation in independent claim 1 of the limitation “assaying a biological sample of the subject to determine…..(d) the genotype of the subject as favorable risk, intermediate-I, intermediate-II, or adverse risk”. First, there is insufficient antecedent basis for the limitation “the genotype”, as this term is not previously employed in the claims. Second, and particularly given this lack of antecedent basis for “the genotype”, it is not clear what “genotype” must be determined “favorable risk, intermediate-I, intermediate-II, or adverse risk” in order to meet the requirements of the claims. While it is noted that the specification discloses preferred embodiments that would appear to be encompassed by this language, specifically with regard to classifying a subject based on “the European LeukemiaNet (ELN) guidelines”, as is discussed in the specification (see, e.g., paragraphs 23-25 and 49-50 of the corresponding published application, as well as Example 1), the term “the genotype” is not, e.g., defined as being limited to this specific type of genotype (and also refers to genotypes of individual mutations, such as those that are present in individual gene of the claims; see, e.g., paragraph 48). Accordingly, further clarification is required with regard to what is encompassed by alternative (d) of claim 1.
Claims 12-17 are indefinite because it is unclear whether independent claim 12 does or does not require performance of the “administering” of c) of the claim, such that there are multiple reasonable interpretations of the claim have different boundaries. Given the recitation of a “method to treat a hematologic cancer” in the claim preamble, and the recitation of a final step of “administering a therapeutically effective amount” of the tested liposomal formulation, some persons of skill in the art would interpret the claims as including a required final “administering” step. However, the wording of b) of claim 12 - stating “measuring the responsiveness of the hematologic cancer cells” - does not clearly require any particular outcome (and specifically an outcome indicating “responsiveness”), while the language of the followed step states “administering….to a subject whose cells respond”, suggesting the possibility that the “administering” is performed with regard to one possible type of subject, with the claim being silent as to any further actions/steps performed with regard to other types of subject (e.g., a subject having an outcome of the “measuring” not indicating “responsiveness”). Accordingly, further clarification is required to ensure that the boundaries of the claims are clear. (It is noted that for purposes of comparing the claimed invention to the prior art, given the indefiniteness and ambiguity noted above, claim 12 is interpreted as reciting an “administering” that is a conditional/contingent step; see MPEP 2111.04(II).)
Claims 3 and 14 are indefinite over the recitation of the limitation “low-cholesterol liposomal formulation” in each of the claims. While it is noted that the specification discloses that a preferred such formulation, CPX-351 “is a nano-scale….low-cholesterol liposome formulation containing cytarabine and daunorubicin co-encapsulated at a 5:1 molar ratio” (see paragraph 3 of the published application) – such that it is clear that CPX-351 meets the requirements of the claims – the term “low-cholesterol” is a relative term that renders the claim indefinite. The term “low-cholesterol” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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) 1-8 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Levine et al (WO 2103/138237 A1 [19 Sept 2013; filed 11 March 2013]; cited herein).
Initially, it is noted that while claims 1-8 are directed to a method “to determining the susceptibility of a hematological cancer-bearing subject to treatment with a liposomal formulation” (see preamble of independent claim 1), “wherein the liposomal formulation comprises cytarabine and daunorubicin co-encapsulated at a synergistic molar ratio” (see the final “wherein” clause of independent claim 1), the language of the claim related to the “liposomal formulation” never recites or otherwise requires any actual use of such a formulation, but rather relates to an inherent property/characteristic of a subject’s cancer that is determined by the active “assaying” of the claim. In other words, the performance of a method comprising “assaying a biological sample to determine” at least one of (a)-(d) of claim 1 inherently accomplishes what is required by the claim preamble and the recited “wherein” language. As such, the intended use of the preamble of determining “susceptibility” to a liposomal formulation as set forth in the “wherein” clause is an intended use that is not given patentable weight when compared the claimed invention to the prior art. See MPEP 2111.02, as well as MPEP 2111.04.
Levine et al teach methods comprising assaying samples (such as blood or bone marrow) from patients with acute myeloid leukemia for mutations in several genes, including FLT3, NPM1, and CEBPA (i.e., each of the genes of a)-c) of independent claim 1); see the entire reference, particularly, e.g., paragraphs 24, 27-30, 35, 38, 97-102, claims 1-17. Levine et al thus anticipate independent claim 1 (as this is sufficient to meet what is required by the claims). While not required for Levine et al to anticipate the present claims, it is also noted that Levine et al further teach that assaying patient samples for mutations in these genes may also aid in determining responsiveness to “high dose therapy”, including responsiveness to daunorubicin (see, e.g., paragraphs 27-30), as well as cytarabine (see, e.g., paragraph 121); Levine et al also teach that the combination of cytarabine and daunorubicin is a known AML therapy (see paragraph 188, although it is reiterated that the present claims do not require any actual use of such a therapy).
With further regard to dependent claims 2-3, these claims are further limiting of the “liposomal formulation”, and thus the practice of the assaying taught by Levine et al meets the requirements of the claims (as again, the claim is directed to a method of detecting presence/absence of a mutation or mutations that are inherently associated with therapy responsiveness, and there is no actual use of any “liposomal formulation” required by these claims). Regarding claims 4-5, Levine et al teach a cancer type and sample type meeting the requirements of the claims, as noted above. Regarding claims 6-8, Levine et al’s teaching of FLT3 mutations is discussed above, and it is noted that preferred mutations disclosed by Levine et al meet the requirements of the claims (see, e.g., paragraphs 21, 24, 38, 97, and 135 teaching FLT3-ITD, as well as the disclosure of both FLT3-ITD and FLT3-TKD in Table 4). Thus, Levine et al anticipate claims 1-8.
Claim(s) 12-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tyner et al (Blood 116:2886 [2010]; cited in IDS), with regard to claim 14, as evidenced by the specification.
Initially, it is reiterated that claims 12-17 are indefinite for the reasons given above, and that the claims have been interpreted as encompassing methods in which the final “administering” is not required, as the broadest reasonable interpretation (BRI) of the language “administering….to a subject whose cells respond to the exposure” at least appears to potentially encompass both methods in which a “responsive” subject is treated and methods in which a nonresponsive subject is not treated. “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met” (MPEP 2111.04(II)).
Tyner et al teach methods in which hematologic cancer cells from subjects having a number of different such cancers – acute myeloid leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, and others – were exposed ex vivo to CPX-351, followed by measurement of the responsiveness of the cells (such as by measuring the IC50 of cells in culture, and well as by evaluating uptake by assessment of daunorubicin cellular fluorescence) (see entire Abstract). Tyner et al teach that CPX-351 “is a liposome formulation of cytarabine (Cyt) and daunorubicin (Daun) in which the ratio of the two drugs (5:1, mol:mol) maximizes synergy” (see first line of “Background”). Tyner et al thus anticipate all of claims 12-13 and 15-17 (as it is noted that Tyner et al disclose that CPX-351 meets the requirements of the preferred embodiment of dependent claim 13, teach cancers meeting the requirements of claim 15, and teach measurement of responsiveness as set forth in claims 16-17 [as stated above]). With further regard to claim 14, given the disclosure of the specification regarding the properties of CPX-351 – see, e.g., paragraph 3 of the published application, which states that CPX-351 “is a nano-scale….low-cholesterol liposome formulation containing cytarabine and daunorubicin co-encapsulated at a 5:1 molar ratio” – Tyner et al’s teaching of CPX-351 also inherently meets the requirements of claim 14, as evidenced by the specification. Accordingly, all of claims 12-17 are anticipated by Tyner et al.
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.
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) 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Levine et al (WO 2103/138237 A1 [19 Sept 2013; filed 11 March 2013]; cited herein) in view of Tyner et al (Blood 116:2886 [2010]; cited in IDS).
Initially, it is again noted that while claim 1 (from which claims 9-11 depend) is directed to a method “to determining the susceptibility of a hematological cancer-bearing subject to treatment with a liposomal formulation” (see preamble of independent claim 1), “wherein the liposomal formulation comprises cytarabine and daunorubicin co-encapsulated at a synergistic molar ratio” (see the final “wherein” clause of independent claim 1), the language of this claim related to the “liposomal formulation” never recites or otherwise requires any actual use of such a formulation, but rather relates to an inherent property/characteristic of a subject’s cancer that is determined by the active “assaying” of the claim. In other words, the performance of a method comprising “assaying a biological sample to determine” at least one of (a)-(d) of claim 1 inherently accomplishes what is required by the claim preamble and the recited “wherein” language. As such, the intended use of the preamble of determining “susceptibility” to a liposomal formulation as set forth in the “wherein” clause is an intended use that is not given patentable weight when compared the claimed invention to the prior art. See MPEP 2111.02, as well as MPEP 2111.04.
Levine et al teach methods comprising assaying samples (such as blood or bone marrow) from patients with acute myeloid leukemia for mutations in several genes, including FLT3, NPM1, and CEBPA (i.e., each of the genes of a)-c) of independent claim 1); see the entire reference, particularly, e.g., paragraphs 24, 27-30, 35, 38, 97-102, claims 1-17. Levine et al thus teach a method meet all of the requirements of claim 1, from which claims 9-11 depend. anticipate independent claim 1 (as this is sufficient to meet what is required by the claims). Levine et al further teach that assaying patient samples for mutations in these (and other) genes may also aid in determining responsiveness to “high dose therapy”, including responsiveness to daunorubicin (see, e.g., paragraphs 27-30), as well as cytarabine (see, e.g., paragraph 121). Levine et al also teach that the combination of cytarabine and daunorubicin is a known AML therapy (see paragraph 188, although it is reiterated that the present claims do not require any actual use of such a therapy). However, Levine et al do not teach methods including additional steps as set forth in claims 9-11, in which hematologic cancer cells from the subject are actually exposed to a liposomal formulation of the type recited in the claims, with responsiveness to the formulation then being measured.
Tyner et al teach methods in which hematologic cancer cells from subjects having a number of different such cancers, including acute myeloid leukemia, were exposed ex vivo to CPX-351, followed by measurement of the responsiveness of the cells (such as by measuring the IC50 of cells in culture, and well as by evaluating uptake by assessment of daunorubicin cellular fluorescence, meeting the requirements of dependent claims 10-11) (see entire Abstract). Tyner et al teach that CPX-351 “is a liposome formulation of cytarabine (Cyt) and daunorubicin (Daun) in which the ratio of the two drugs (5:1, mol:mol) maximizes synergy” (see first line of “Background”); i.e., a liposomal formulation meeting the requirements of the claims. Tyner et al further teach that combining “such in vitro cytotoxicity information with other forms of phenotypic and/or genomic data may also reveal biomarkers that are predictive of response to CPX-351 therapy” (see “Conclusions”).
In view of the teachings of Tyner et al, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods of Levine et al so as to have performed further testing regarding cancer responsiveness to possible therapies, including of responsiveness to CPX-351 – which meets the requirements of a “liposomal formulation” set forth in the claims - via the steps taught by Tyner et al, and thereby to have performed a method meeting the requirements of claims 9-11. An ordinary artisan would have been motivated to have performed such further testing by Tyner et al’s suggestion that combining their testing with “other forms of phenotypic and/or genomic data” – i.e., testing and data of the type taught by Levine et al with regard to the treatment of the same type of cancer – may aide in determination of response to CPX-351. Furthermore, given the detail guidance provided by both Levine et al and Tyner et al, an ordinary artisan would have had a reasonable expectation of success in performing such a method.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Independent claim 1 (from which claims 2-11 depend) recites a method “to determine the susceptibility of a hematologic cancer-bearing subject to treatment with a liposomal formulation” as defined in the claim, where the method comprises “assaying a biological sample of the subject” to determine one or more of a)-d) (reciting different mutations or “the genotype” as set forth in the claim). The activity of “determining the susceptibility” encompasses, e.g., thinking about the results of the “assaying” and drawing a conclusion therefrom regarding susceptibility, i.e., an activity that may be performed entirely in the human mind, which is a type of abstract idea.
This judicial exception is not integrated into a practical application because the sole active step of “assaying a biological sample to determine” presence or absence of one or more mutations or “the genotype” of d) are data gathering steps that do not add a meaningful limitation to the method as they are insignificant extra-solution activity. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the “assaying” of the claims clearly constituted well-understood, routine, and conventional activity before Applicant’s effective filing date (see, e.g., Levine et al, cited above). With further regard to dependent claims 2-3, these claims set forth further limitations of the “liposomal formulation” of claim 1, which is an element of the abstract idea of the claim (i.e., the claim is directed to determining susceptibility of this formulation, but does not employ or require any use of it); nothing amounting to a practical application, or something “more” than a JE, is added by these claims. Dependent claim 4 recites a type of cancer from which data is to be gathered (rather than any kind of action/implementation of a JE, or something “significantly more” than a JE). Claim 5 requires the gathering of data from a more particular type of sample; however, the use of such samples was well-understood, routine, and conventional before Applicant’s effective filing date (see, e.g., Levine et al), and nothing constituting an application of a JE is recited. Claims 6-8 recite further limitations on a gene or mutation for “assaying”; however, these claims again recite a more specific type of data gathering (rather than any kind of application/implementation of a JE), and such activities were also well-known, routine, and conventional (see again Levine et al). Accordingly, none of claims 1-8 is directed to patent eligible subject matter.
(With regard to dependent claims 9-11, it is noted that those claims were not included in the present rejection because the combination of active steps required by the claims -including the “assaying” of independent claim 1, and the further ex vivo testing of claim 9- was not found to be well-understood, routine, and conventional before the effective filing date of the claimed invention.)
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DIANA B JOHANNSEN whose telephone number is (571)272-0744. The examiner can normally be reached Monday-Friday, 7:30 am-3:30 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682