DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-5, 8-13, 16 and 19-24 are pending in this application.
Applicant’s amendment to the claims filed 05/12/2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed on 05/12/2026 in response to the non-final rejection mailed on 01/16/2026 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is:
Species A, synergistic therapeutic effect,
Species B, polyethylene glycosylated Erwinia chrysanthemi-derived asparaginase (pegcrisantaspase, PegC),
Species C, Venetoclax (Ven), and
Species D, acute myeloid leukemia (AML),
elected without traverse in the reply filed 07/15/2024.
Claims 1-5, 8-13, 16 and 19-24 are being examined on the merits only to the extent they read on the elected subject matter.
Claim Rejections - 35 USC § 103
Claims 1, 5, 9-11 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Emadi et al. (Cancer Chemother Pharmacol, 2018, 81:217; cited on the IDS submitted 06/17/2021; herein Emadi) in view of Peirs et al. (Lymphoid Neoplasia, 2014, 124:3738; cited on the Form PTO-892 mailed 01/16/2026; herein Peirs) and Leonard et al. (Sci Transl Med, 2016, 8:354ra114; cited on the Form PTO-892 mailed 01/16/2026; herein Leonard).
The instant rejection is maintained from the previous office action, and any newly recited portion is necessitated by amendment.
Claim 1 is drawn to a method of treating acute myeloid leukemia (AML) in a subject or prolonging survival of a subject having AML, comprising administering synergistically therapeutic amount of a first agent that depletes plasma glutamine and a second agent that inhibits BCL-2 activity to a subject having AML.
Emadi discusses asparaginase Erwinia chrysanthemi that effectively depletes plasma glutamine in patients with acute myeloid leukemia (AML) [title], and discusses the potential for the enzyme’s activity to produce glutamine deprivation as a therapeutic approach to AML via targeting the reliance of AML cells on glutamine [p 217, col 2, para 1 to p 218, col 2, para 1].
Regarding the limitation in claim 1 of an agent that depletes plasma glutamine, Emadi teaches the depletion of glutamine as a therapeutic approach to treatment of AML, and that asparaginase derived from Erwinia chrysanthemi has the greatest glutaminase activity of the available asparaginases [abstract].
Emadi further discusses that routine treatment for younger patients with AML is a combination chemotherapy with cytarabine and an anthracycline [p 217, col 2, para 1], wherein cytarabine is understood in the art to be an antimetabolite treatment, and anthracyclines are understood in the art to induce cell death. Therefore Emadi recognizes that it was routine in the field to treat AML by combining an antimetabolite treatment with a treatment to induce cell death, and suggests the use of the disclosed asparaginase above as the antimetabolite.
Emadi does not teach the use of a BCL-2 inhibitor, or a synergistic therapeutic amount of a first and a second agent in a treatment of AML.
Peirs relates to ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia [title], and discusses targeted therapeutics against hematologic malignancies such as ABT-199 can potentially improve patient prognosis and survival [p 3738, col 2, final para].
Regarding claim 1 and the limitation of a synergistically therapeutic amount of a first and second agent, Peirs teaches ABT-199 shows synergistic therapeutic effects with different chemotherapeutic agents, wherein ABT-199 is disclosed as the BCL-2 inhibitor venetoclax by Leonard [abstract] with impressive activity against hematologic malignancies such as AML by selectively inhibiting BCL-2, wherein the inhibition of the antiapoptotic BCL-2 is understood to result in the induction of cell death or apoptosis [p 1, col 2, paras 2-3 of Leonard]. Piers further discloses that the chemotherapeutic agents used in the combinatorial treatment with ABT-199 include the L-asparaginase [abstract] Erwinase, PL 01511/0272 [Peirs, p 3740, col 1, Section “Combination treatment of cells with ABT-199 and chemotherapeutic agents]. Additionally, Peirs shows the identification of synergistic combinations of ABT-199 and asparaginase concentrations against leukemia cell lines in [Figure 6B], which is considered to encompass synergistically therapeutic amounts of a first agent and a second agent recited in claim 1.
In view of Emadi, Peirs and Leonard, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Emadi by administering an asparaginase with a BCL-2 inhibitor, as taught by Peirs and Leonard, and comprising synergistically therapeutic amounts of a first agent and a second agent, as taught by Peirs, to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to modify the method of Emadi by using a BCL-2 inhibitor, because Emadi teaches it was routine in the field to treat AML by combining an antimetabolite treatment such as asparaginase with a treatment to induce cell death, Leonard teaches that venetoclax is a BCL-2 inhibitor used to induce cell death in AML treatments, and Peirs teaches a combination therapy of venetoclax and asparaginase to treat leukemia cells.
One of ordinary skill in the art would have been motivated to modify the method of Emadi by using synergistically therapeutic amounts of a first and second agent because Peirs teaches the determination of synergistic amounts of venetoclax and asparaginase for combination treatment of leukemia cells.
One of ordinary skill in the art would have had a reasonable expectation of success because Emadi and Peirs discuss combination therapy for leukemia treatment comprising the administration of asparaginase and an agent to increase cell death, and Emadi, Peirs and Leonardo discuss treatments of hematologic malignancies such as leukemia with an agent to induce cell death.
Regarding claim 5, Peirs teaches the asparaginase is prepared in a 0.9% NaCl solvent [p 3740, col 1, para 5], which is considered to be encompassed by the limitation of an agent formulated in a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent.
Regarding claim 9, Emadi teaches a dosage of 25,000 IU/m2 asparaginase [p 219, col 1, para 2].
Regarding claims 10 and 20, Peirs teaches the use of venetoclax.
Regarding claim 11, Peirs teaches the administration of concentrations of venetoclax ranging approximately 1 to 20,000 nM [Figure 6B] in 100 µL volumes [p 3739, col 2, para 2]. As the molecular weight of venetoclax is understood to be approximately 868 g/mol, the range of venetoclax taught by Peirs corresponds to a range of approximately 86.8 to 173,000 mg, and according to MPEP 2144.05.I, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.
Therefore, the invention of claims 1, 5, 9-11 and 20 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 2-4, 13, 16 and 21-22 are newly rejected under 35 U.S.C. 103 as being unpatentable over Emadi in view of Peirs and Leonard as applied to claims 1, 5, 9-11 and 20 above, and further in view of Mrozek et al. (Seminars Oncol, 2008, 35:365; cited on the attached Form PTO-892; herein Mrozek).
The instant rejection is newly stated and necessitated by claim amendment.
Claim 2 (claims 3-4 dependent therefrom) is drawn to the method of claim 1, wherein the AML is complex karyotype AML (CK-AML).
Claim 13 (claim 21 dependent therefrom) is drawn to a method of treating CK-AML, comprising administering synergistically therapeutic amounts of an asparaginase and venetoclax to a subject having CK-AML.
Claim 16 (claim 22 dependent therefrom) is drawn to a method of prolonging survival of a subject having CK-AML, comprising administering synergistically therapeutic amounts of an asparaginase and venetoclax to a subject having CK-AML.
The teachings of Emadi, Peirs and Leonard as applied to claims 1, 5, 9-11 and 20 are discussed above, and include the treatment of AML with synergistically therapeutic amounts of an asparaginase and venetoclax. These references do not teach the treatment of CK-AML.
Mrozek relates to cytogenic, molecular genetic, and clinical characteristics of acute myeloid leukemia with a complex karyotype [title], and describes a patient with AML and three or more acquired chromosome aberrations that are not from a defined prognostically favorable category are considered to have AML with complex karyotype [abstract].
Regarding claim 2, Mrozek discusses a number of chromosome aberrations associated with CK-AML [abstract, and Table 1] and describes the loss of the gene TP53 that likely plays a role in leukemogenesis in CK-AML patients, wherein TP53 encodes a tumor suppressor gene whose loss results in genetic instability and increased cell survival [p 368, col 2, penultimate paragraph, to p 369, first paragraph]. As Piers and Leonard teach the BCL-2 inhibitor venetoclax shows impressive activity against hematologic malignancies by selectively inhibiting BCL-2, wherein the inhibition of the antiapoptotic BCL-2 is understood to result in the induction of cell death or apoptosis [p 1, col 2, paras 2-3 of Leonard], one of skill in the art would be expected to reason that the combination could be used to treat CK-AML particularly in view of the teachings of Mrozek that most CK-AML patients have a mutation and/or loss of the tumor suppressor gene TP53 and resulting increased cell survival [p 369, col 1, para 1 of Mrozek].
In view of Mrozek, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Emadi, Peirs and Leonard by using the method to treat CK-AML, as suggested by Peirs, Leonard and Mrozek, to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to modify the combined method of Emadi, Peirs and Leonard by treating CK-AML, because Mrozek teaches most CK-AML patients show a mutation and/or loss of TP53 resulting in increased cell survival, and Peirs and Leonard teach the use of the BCL-2 inhibitor venetoclax in hematological malignancies that would include AML to induce cell death.
One of ordinary skill in the art would have had a reasonable expectation of success because Emadi and Mrozek relate to types of AML, Piers and Emadi relate to leukemia treatments comprising agents to induce cell death, Piers and Leonard relate to BCL-2 inhibitors that induce cell death, and Mrozek teaches a genetic characteristic of CK-AML is a genetic mutation prevents cell death.
Regarding claim 3-4, the combined method of Emadi, Peirs, Leonardo and Mrozek as described above is considered to encompass a concurrent administration of a combination of first and second agents with overlapping periods of administration, as Peirs teaches the addition of ABT-199 and chemotherapeutic (venetoclax) to cell lines [p 3740, col 1, para 5].
Regarding claim 13, the combined method of Emadi, Peirs, Leonardo and Mrozek as discussed in the rejection of claim 2 above teaches the limitation of treating a subject with CK-AML by administering asparaginase to reduce glutamine plasma levels and a BCL-2 inhibitor to said subject [Emadi, abstract; Peirs abstract and p 3740, col 1, Section “Combination treatment of cells with ABT-199 and chemotherapeutic agents]. Therefore it would have been obvious to one of skill in the art before the effective filing date to use the asparaginase and BCL-2 inhibitor of Peirs in the combined method of Emadi, Peirs, Leonardo, and Mrozek to treat CK-AML, as suggested by Peirs, Leonard and Mrozek, to arrive at the claimed invention.
Regarding claim 16, the combined method of Emadi, Peirs, Leonardo and Mrozek as discussed in the rejection of claim 2 above teaches the limitation of treating a subject with CK-AML by administering asparaginase to reduce glutamine plasma levels and a BCL-2 inhibitor to said subject [Emadi, abstract; Peirs abstract and p 3740, col 1, Section “Combination treatment of cells with ABT-199 and chemotherapeutic agents]. Peirs additionally teaches the use of the synergistically therapeutic amounts of the BCL-2 inhibitor venetoclax with the L-asparaginase Erwinase [abstract, p 3740, col 1, Section “Combination treatment of cells with ABT-199 and chemotherapeutic agents, and Figure 6], wherein the increased synergism shown in Fig. 6 corresponds to decreased viability of leukemia cell lines, which is considered to correspond to prolonged survival of a subject. As Leonard teaches that venetoclax shows activity against hematologic malignancies such as AML [p 1, col 1, final para], it would have been obvious to one of skill in the art before the effective filing date to use the asparaginase and BCL-2 inhibitor of Peirs in the combined method of Emadi, Piers, Leonard and Mrozek, to prolong survival of a subject having CK-AML, as suggested by Peirs, to arrive at the claimed invention.
Regarding claim 21 (dependent from claim 13), the combined method of Emadi, Peirs and Leonard and is considered to encompass a concurrent administration of a combination of first and second agents with overlapping periods of administration, as Peirs teaches the addition of ABT-199 and chemotherapeutic (venetoclax) to cell lines [p 3740, col 1, para 5].
Regarding claim 22 (dependent from claim 16), the combined method of Emadi, Peirs and Leonard and is considered to encompass a concurrent administration of a combination of first and second agents with overlapping periods of administration, as Peirs teaches the addition of ABT-199 and chemotherapeutic (venetoclax) to cell lines [p 3740, col 1, para 5].
Therefore, the invention of claims 2-4, 13, 16 and 21-22 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 8, 19 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Emadi in view of Peirs and Leonard as applied to claims 1, 5, 9-11 and 20 above, and further in view of Chien et al. (Invest New Drugs, 2014, 32:795; cited on the Form PTO-892 mailed 01/16/2026; herein Chien).
The instant rejection is maintained from the previous office action, any newly recited portion is necessitated by claim amendment.
Claim 8 is drawn to the method of claim 1, wherein the agent that depletes plasma glutamine is polyethylene glycosylated Erwinia chrysanthemi-derived asparaginase (PegC).
The teachings of Emadi, Piers and Leonard as applied to claims 1, 5, 9-11 and 20 are discussed above. These references do not teach the enzyme PegC.
Chien relates to the pharmacology and efficacy of novel pegylated recombinant Erwinia chrysanthemi-derived L-asparaginase [title].
Regarding claims 8 and 19, Chien teaches bacterial L-asparaginases are an indispensable component of the treatment of acute lymphoblastic leukemia, and that pegylated recombinant crisantaspase from Erwinia chrysanthemi-derived L-asparaginase shows anti-leukemic activity [abstract]. Therefore the enzyme of Chien is considered to correspond to the polyethylene glycosylated Erwinia chrysanthemi-derived asparaginase recited in the claims.
In view of Chien, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Emadi, Peirs and Leonard by using the enzyme of Chien to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the asparaginase of Emadi and the enzyme of Chien are both asparaginase enzymes used for the treatment of leukemia, and as such both are capable of being incorporated into such methods as described by Emadi. Thus it would have been obvious to one of ordinary skill in the art to replace the asparaginase of Emadi with the asparaginase of Chien, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the Emadi and Chien discuss the use of asparaginases in leukemia treatments.
Regarding claim 23, the method of claim 23 limits the polyethylene glycosylated E. coli-derived asparaginase in the method of claim 8, but does not limit the method of claim 8 to comprise a polyethylene glycosylated E. coli-derived asparaginase. Therefore the method as recited in claim 23 still encompasses all of the alternatives of claim 8, including E. coli-derived short acting asparaginase, polyethylene glycosylated E. coli-derived asparaginase, Erwinia chrysanthemi-derived short acting asparaginase, and polyethylene glycosylated Erwinia chrysanthemi-derived asparaginase. Therefore the combination used to reject claim 8 is also used for claim 23. If the applicant intends to limit the method of claim 23 to comprise a polyethylene glycosylated E. coli-derived asparaginase, the applicant should consider an amendment to recite "the method of claim 8 comprising a polyethylene glycosylated E. coli-derived asparaginase".
Therefore, the invention of claims 8, 19 and 23 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 12 is newly rejected under 35 U.S.C. 103 as being unpatentable over Emadi in view of Peirs, Leonard and Mrozek as applied to claims 1-5, 9-11, 13, 16 and 20-22 above, and further in view of DiNardo et al. (Am J Hematol, 2018, 93:401; cited on the attached Form PTO-892; herein DiNardo).
The instant rejection is newly stated and necessitated by claim amendment.
Claim 12 is drawn to the method of claim 1, wherein the AML is relapsed/refractory (R/R) AML.
The teachings of Emadi, Peirs, Leonard and Mrozek as applied to claims 1-5, 9-11, 13, 16 and 20-22 are discussed above, and include the treatment of AML and CK-AML with synergistically therapeutic amounts of an asparaginase and venetoclax. These references do not teach the treatment of relapse/refractory AML.
DiNardo relates to the use of venetoclax in combination therapy for relapsed and refractory AML and related myeloid malignancies [title], and discusses the subgroup of AML patients that have R/R-AML which has comparatively limited therapeutic options [p 401, cols 1-2].
Regarding claim 12, DiNardo teaches the use of venetoclax in a combination therapy for patients with R/R-AML that shows impressive response rates and outcome data [p 404, col 2, penultimate paragraph], and includes combination of venetoclax with LDAC [p 405, col 2, final paragraph], wherein LDAC is low-dose cytarabine [p 402, col 1, para 3]. As stated in the rejection of claim 1 above, Emadi teaches the use of cytarabine [p 217, col 2, para 1] that is understood in the art to be an antimetabolite, and therefore suggests the use of asparaginase as the antimetabolite portion of the routine combination therapy for AML comprising antimetabolite treatment with a treatment to induce cell death.
Regarding claim 12 and pegC, Chien teaches bacterial L-asparaginases are an indispensable component of the treatment of acute lymphoblastic leukemia, and that pegylated recombinant crisantaspase from Erwinia chrysanthemi-derived L-asparaginase shows anti-leukemic activity [abstract]. Therefore the enzyme of Chien is considered to correspond to the polyethylene glycosylated Erwinia chrysanthemi-derived asparaginase recited in the claims.
In view of DiNardo, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Emadi, Peirs, Leonard and Mrozek by using the method to treat R/R AML, as taught by DiNardo, to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to modify the combined method of Emadi, Peirs, Leonard and Mrozek by treating R/R AML, because DiNardo teaches a method of treating R/R AML patients with venetoclax in a combination therapy with an antimetabolite resulting in impressive response rates and outcome data, and Emadi suggests the use of asparaginase for the antimetabolite in such treatments.
One of ordinary skill in the art would have had a reasonable expectation of success because Emadi and DiNardo relate to types of AML and combination therapy treatments thereof.
In view of Chien, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Emadi, Peirs, Leonard, Mrozek and DiNardo by using the enzyme of Chien to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both the asparaginase of Emadi and the enzyme of Chien are both asparaginase enzymes used for the treatment of leukemia, and as such both are capable of being incorporated into such methods as described by Emadi. Thus it would have been obvious to one of ordinary skill in the art to replace the asparaginase of Emadi with the asparaginase of Chien, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the Emadi and Chien discuss the use of asparaginases in leukemia treatments.
Therefore, the invention of claim 12 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 24 is newly rejected under 35 U.S.C. 103 as being unpatentable over Emadi in view of Peirs, Leonard, Mrozek and DiNardo as applied to claims 1-5, 9-13, 16 and 20-22 above, and further in view Chien.
The instant rejection is newly stated and necessitated by claim amendment.
Claim 24 is drawn to the method of claim 2, wherein the CK-AML is relapsed/refractory AML, wherein the agent that depletes plasma glutamine is PegC, and wherein the agent that inhibits BCL-2 activity is venetoclax.
The teachings of Emadi, Peirs, Leonard, Mrozek and DiNardo as applied to claims 1-5, 9-13, 16 and 20-22 are discussed above, and include the treatment of AML, R/R AML, and CK-AML with synergistically therapeutic amounts of an asparaginase and venetoclax. These references do not teach the treatment of R/R-CK-AML and the use of PegC.
Regarding claim 24, the combined method of Emadi in view of Peirs, Leonard, Mrozek and DiNardo as discussed in the rejection of claim 12 corresponds to the treatment of R/R AML with venetoclax and an antimetabolite that is an asparaginase, wherein DiNardo teaches the venetoclax+antimetabolite combination shows impressive response rates and outcome data to R/R patients with comparatively limited therapeutic options. DiNardo further describes the importance of targeting BCL-2 activity in AML patients with inhibitors to combat the maintenance and survival of AML cells [p 402, col 1, para 2]. As Mrozek identifies most CK-AML patients have a mutation and/or loss of the tumor suppressor gene TP53 and resulting increased cell survival [p 369, col 1, para 1 of Mrozek], Mrozek identifies the lack of cell survival control to play a role in CK-AML patients similar to that identified by DiNardo in patients with AML in general, and with those having R/R AML.
In view of Mrozek and DiNardo, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Emadi, Peirs, Leonard, Mrozek and DiNardo by using the method to treat R/R CK-AML, as suggested by DiNardo and Mrozek, to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to the combined method of Emadi, Peirs, Leonard, Mrozek and DiNardo by treating R/R CK-AML, because Mrozek identifies the lack of cell survival control due to mutation and/or loss of tumor suppressor genes plays a role in CK-AML, and DiNardo teaches the importance of inhibiting BCL-2 activity which induces cell death in AML patients and the impressive response rates and outcome data from doing so in R/R AML patients.
One of ordinary skill in the art would have had a reasonable expectation of success because DiNardo and Mrozek relate to deficiencies in different AML patient populations with regards to controlling growth of leukemia cells, and DiNardo, Emadi and Peirs relate to the treatment of AML with BCL-2 inhibitors as part of a therapeutic strategy for treatment of leukemias.
Therefore, the invention of claim 24 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks: beginning on page 5 of Applicant’s response to rejections under 35 USC 103; Applicant in summary contends Peirs and Leonard relate to the treatment of acute lymphoblastic leukemia (ALL) while Emadi relates to the treatment of acute myeloid leukemia (AML), and that treatments for ALL cannot be routinely expected to also work for AML as the two are drawn to different fast-growing cell types that affect different patient populations; Applicant further contends the claimed invention displays unexpected results as shown in paras 0120-0121 and Example 6 of the instant specification such as the synergy between the claimed agents; Applicant further contends it is difficult to predict synergy among agents, lending to the unpredictability of the results shown in Figures 6A, 6B and 6C and explained in Example 6 of the specification; Applicant further contends the Examiner recognized the surprising unexpected and significant nature of the experimental data on page 12 of the office action mailed 01/16/2026 that correspond to results for AML, and therefore the amendments to the claims regarding the treatment of AML should be commensurate in scope with the results.
Applicant’s remarks are considered and found not convincing.
Regarding the assertion that treatments for ALL cannot be routinely expected to also work for AML as the two are drawn to different fast-growing cell types that affect different patient populations: The argument for a reasonable expectation of success in combining the teachings of Emadi, Peirs and Leonard set forth in the rejection above is not based on whether said method would be routinely expected to work for AML. Rather, the expectation is based on the preponderance of evidence which requires the evidence to be more convincing than the evidence which is offered in opposition to it according to MPEP 2142. As Emadi, Peirs and Leonard are drawn to treatments of different types of leukemia (ALL and AML) as noted by Applicant, the disclosed treatments for each leukemia comprise agents that induce cell death such as BCL-2 inhibitors (Peirs and Leonard) and anthracyclines (Emadi). Therefore, one of ordinary skill in the art would have had a reasonable expectation of success in using the BCL-2 inhibitor of Peirs and Leonard to treat AML in the method of Emadi.
Regarding Applicant’s assertion of unexpected results:
According to MPEP 716.02(b), the burden is on applicant to establish results are unexpected and significant, and that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance. MPEP 716.02(b) also states applicants have the burden of explaining the proffered data. As Applicant asserts it is difficult to predict synergy among agents, lending to the unpredictability of the results shown in Figures 6A, 6B and 6C and explained in Example 6 of the specification, there is no explanation of why said results are unpredictable, unobvious, statistically significant or practically significant, as the plain recitation of results shown in a figure and the statement that results “would not have been reasonably predictable by one of ordinary skill in the art” do not amount to an explanation or an establishment that results are unexpected and significant, and that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance. Therefore the requirements of MPEP 716.02(b) are not satisfied.
According to MPEP 716.02(e), unexpected results must be compared with the closest prior art. As the data proffered by Applicant is found in the instant specification, there is no comparison with any prior art. Therefore the requirements of MPEP 716.02(e) are not satisfied.
According to MPEP 716.02(d), unexpected results must be commensurate in scope with the claimed invention. The scope of the invention of claim 1 reciting “A method of treating AML in a subject or prolonging survival of a subject having AML, comprising administering synergistically therapeutic amounts of a first agent that depletes plasma glutamine and a second agent that inhibits BCL-2 activity to a subject having AML” the treatment of all subjects with AML with all agents that deplete plasma glutamine and all BCL-2 inhibitors, as well as the result of treatment of AML and prolonged survival of a subject with AML. As the results proffered by Applicant in paras 0120-0121 and Example 6 correspond to results in AML cell lines and mouse models treated with a combination of venetoclax and PegC, the results are not commensurate in scope with the invention of claim 1. Therefore the requirements of MPEP 716.02(d) are not satisfied.
For these reasons, Applicant’s assertion of unexpected results are not sufficient to rebut a prima facie case of obviousness.
Regarding the assertion that the Examiner recognized the surprising unexpected and significant nature of the experimental data on page 12 of the office action mailed 01/16/2026 that correspond to results for AML: there is no recognition of surprising unexpected and significant nature of the experimental data on page 12 of the office action mailed 01/16/2026, as the section Applicant references is the response to the Applicant’s allegations of unexpected results, particularly the discussion of the proffered data accompanying said allegations and how the allegations do not satisfy the requirements of MPEP 716.02(d) and MPEP 716.02(e).
Conclusion
Status of the Application:
Claims 1-5, 8-13, 16 and 19-24 are pending.
Claims 1-5, 8-13, 16 and 19-24 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
Prosecution Insights