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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/04/2025 has been entered.
Applicant' s amendment and response filed on 11/04/2025 has been received and entered into the case.
Amendments
In the reply filed on 11/04/2025, Applicant has amended claim 61.
Claim Status
Claims 61-62 and 69-84 are pending.
Claims 62, 69, 71-72, 75 and 84 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/07/2025.
Claims 61, 70, 73-74 and 76-83 are considered on the merits.
Withdrawn Claim Objections
The prior objection to claim 61 because of missing the term “kinase” is withdrawn in light of Applicant’s amendment to the claim.
Reminder of Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
In the instant case, the limitation in claim 61 (a) “a means for inhibiting BCR-ABL tyrosine kinase” is being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, and is limited by the description in the specification (page 39, para [000130], i.e., the same as para [0127] in US20240263135A1, see also instant Remarks, pages 6-7), which recites the means being BCR-ABL tyrosine kinase inhibitors (TKI) that are small molecule inhibitors such as DCC-2036 and dasatinib.
Response to Traversal:
Applicant’s arguments filed on 11/04/2025 are acknowledged.
Applicant agrees with construing the "means for inhibiting BCR-ABL tyrosine kinase" as a "means-plus-function" term, but argues that “paragraph [0127] is not the only disclosure in US20240263135A1 relevant to such construction. Disclosure elsewhere in the application relating to means for inhibiting BCR-ABL tyrosine kinase, and equivalents thereof, should also be considered in the construction of this term, in accordance with 35 U.S.C. 112(f)” (Remarks, p 7, para 1).
Applicant’s arguments have been fully considered but they are not persuasive. Although Examiner agrees that the broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked, paragraph [0127] is the most comprehensive and inclusive paragraph that describes the means for inhibiting BCR-ABL tyrosine kinase (and thus was selected in the prior Office action). The only other places in the disclosure relating to means for inhibiting BCR-ABL tyrosine kinase are in paragraph [0140] reciting the composition comprises “a BCR-ABL tyrosine kinase inhibitor” and Table 1 reciting Bcr-Abl tyrosine-kinase inhibitor for example DCC-2036 and Table 2 reciting DCC-2036 being BCR-ABL inhibitor. Thus, the limitation “a means for inhibiting BCR-ABL tyrosine kinase” is being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, to be limited by the description in the specification, specifically in para. [0127], [0140], Tables 1 and 2 in US20240263135A1, as BCR-ABL tyrosine kinase inhibitors (TKI) that are small molecule inhibitors such as DCC-2036 and dasatinib. Applicant is invited to specifically point out the disclosure in the instant specification relevant to the construction of the term.
Withdrawn Claim Rejections - 35 USC § 102(a)(1)
The prior rejection of claims 61, 70, 73-74, 78-79 and 82-83 under 35 U.S.C. 102 (a)(1) as being anticipated by Schade et al., (Blood. 2008;111:1366-1377) is withdrawn in light of Applicant’s amendment to claim 61 to recite new limitation “the composition does not comprise animal serum”, which is not taught by Schade.
Withdrawn Claim Rejections - 35 USC § 103
The prior rejection of claims 61, 70, 73-74, 76 and 78-83 under 35 U.S.C. 103 as being unpatentable over Schade et al., (Blood. 2008;111:1366-1377) in view of Themeli et al (WO 2014/165707A2, also published as US20160009813A1, cited in IDS 04/26/2024) is withdrawn in light of Applicant’s amendment to claim 61 to recite new limitation “the composition does not comprise animal serum”, which is not taught by Schade.
The prior rejection of claims 61, 70, 73-74, 77, 78-79 and 82-83 under 35 U.S.C. 103 as being unpatentable over Schade et al., (Blood. 2008;111:1366-1377) in view of Chan et al (Cancer Cell. 2011; 19: 556-568. Cited in IDS 04/26/2024) is withdrawn in light of Applicant’s amendment to claim 61 to recite new limitation “the composition does not comprise animal serum”, which is not taught by Schade.
New Claim Rejections - 35 USC § 102(a)(1)
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 –
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.
Claims 61, 70, 73-74, 78 and 82 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Fei et al., (Exp Hematol. 2008;36(10):1297-1308).
With respect to claim 61, it is noted that the limitation “for preparing a pharmaceutical composition” in preamble and the wherein clauses in (e) are directed to an intended use. MPEP 2111.02 II states “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. Accordingly, the limitations in preamble and the wherein clauses in (e) do not provide any patentable weight in determining patentability of the claimed composition. Thus, claim 61 is reasonably interpreted as a composition in vitro, being capable of preparing a pharmaceutical composition, wherein the composition comprises a population of human immune cells (see limitation (f)) comprising T cells (see limitation (d)), a means for inhibiting BCR-ABL tyrosine kinase that is one of BCR-ABL tyrosine kinase inhibitors (TKI) including DCC-2036 or dasatinib, and a pharmaceutically acceptable medium (see limitation (a)), the composition does not comprise animal serum (see limitation (c)), the BCR-ABL TKI is effective to produce modulated immune cells (see limitation (b)) and increase the number or ratio of one or more subpopulations comprising T cells expressing one or both of CD62L and CCR7 (see limitation (d)) upon culturing in the pharmaceutically acceptable medium.
Fei teaches BCR-ABL tyrosine kinase inhibitor dasatinib or imatinib exerts an immunosuppressive effect on CD8+ T cells specific for viral and leukemia antigens (see e.g., abstract). Fei teaches CD8+ T cells are isolated from blood samples of heathy donors or patients under dasatinib medication and are cultured in RPMI-1640 supplemented with 10% human AB serum with dasatinib or imatinib (see e.g., p. 1298, left col, para “CD8+ T-cell isolation and culture” for source and the culture medium and see “CFSE proliferation assay”, “Apoptosis assay” and “Cell-cycle analysis” for culture with dasatinib or imatinib), thus teaches a composition in vitro, wherein the composition comprises a population of human immune cells (i.e., isolated from heathy donors or patients, related to limitation (f)) comprising T cells (i.e., CD8+ T cells, related to limitation (d)), a means for inhibiting BCR-ABL tyrosine kinase that is one of BCR-ABL tyrosine kinase inhibitors (i.e., dasatinib or imatinib), and a pharmaceutically acceptable medium (i.e., RPMI-1640 supplemented with 10% human AB serum, related to limitation (a)), the BCR-ABL TKI is effective to produce modulated immune cells upon culturing in the pharmaceutically acceptable medium (e.g., Dasatinib inhibits proliferation of CD8+T cells in a dose-dependent manner, see e.g., abstract, related to limitation (b)), and the composition does not comprise animal serum (i.e., comprises human AB serum, related to limitation (c)).
Regarding the composition being capable for preparing a pharmaceutical composition, Fei teaches using clinically relevant doses of dasatinib according to published serum levels achieved in patients taking 70 mg dasatinib twice daily (p. 1299, left col, “Results” section, para 1) and acknowledges that Schade et al. showed that T cells not only survive dasatinib treatment, but they remained capable of being activated in its presence by stimuli bypassing the TCR (see p. 1306, right col, para 2). Accordingly, Fei teaches the composition comprises both dasatinib and T cells, that is in clinically relevant dose and are capable of being activated, respectively, thus the composition is capable for preparing a pharmaceutical composition.
Regarding limitation (d), it is noted that there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. See MPEP 2112 II. Additionally, MPEP 2145 (II) states that “mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention”, and “the fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.” Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985)”. In the instant case, the prior art Fei teaches the claimed composition comprising a population of human T cells, a BCR-ABL TKI dasatinib, and a pharmaceutically acceptable medium free of animal serum, and teaches the BCR-ABL TKI is effective to produce modulated immune cells upon culturing in the pharmaceutically acceptable medium. Thus, the fact that Applicants have recognized another advantage (i.e., the BCR-ABL TKI is effective to increase the number or ratio of one or more subpopulations comprising T cells expressing one or both of CD62L and CCR7 upon culturing in the pharmaceutically acceptable medium in limitation (d)) cannot be the basis for patentability when the claimed composition is disclosed by Fei. Furthermore, this subject matter (limitation (d)) would be in fact inherent in the prior art reference since Fei teaches the same composition comprising the same three components (i.e., human T cells, BCR-ABL TKI, and medium free of animal serum) as that being claimed. Additionally, since Fei’s composition comprises T cells that are modulated by the BCR-ABL TKI, and inherently have increased number or ratio of one or more subpopulations comprising T cells expressing one or both of CD62L and CCR7 upon culturing in the pharmaceutically acceptable medium, the composition of Fei is capable for preparing a pharmaceutical composition that comprises T cells expressing one or both of CD62L and CCR7 in limitation (e). Since the Patent Office does not have the facilities for examining and comparing applicants' composition with the composition of the prior art reference, the burden is upon applicants to show a distinction between the material structural and functional characteristics of the claimed composition and the composition of the prior art. See MPEP 2112 V.
With respect to claim 70 directed to the T cells comprising various types of T cells, it is noted that this limitation is drawn to the T cells in claim 61 (d) (i.e., T cells expressing one or both of CD62L and CCR7 that are markers for naïve T cells and central memory T cells) and is directed to an inherent feature in the prior art Fei as discussed above. Thus, the composition of Fei anticipates the composition in claim 70.
With respect to claim 73 directed to the immune cells comprising cells obtained by differentiating stem cells, and claim 74 directed to the stem cells being embryonic stem cells, as stated supra, Fei teaches the CD8+ T cells are isolated from blood samples of heathy donors or patients under dasatinib medication (see e.g., p. 1298, left col, para “CD8+ T-cell isolation and culture”), which are necessarily differentiated from embryonic stem cells.
With respect to claim 78 directed to the T cells having at least one of a list of characteristics, it is noted that this limitation is drawn to other advantages recognized by Applicants, similar to the limitation in claim 61 (d) as discussed above, and thus is directed to inherent features of the composition in the prior art Fei. Thus, the composition of Fei anticipates the composition in claim 78.
With respect to claim 82 directed to the T cells comprising CD8+ T cells, as stated supra, Fei teaches CD8+ T cells are isolated and cultured (see e.g., p. 1298, left col, para “CD8+ T-cell isolation and culture”).
Accordingly, Fei anticipates instant claims.
Response to Traversal:
Applicant’s arguments filed on 11/04/2025 are acknowledged.
Applicant argues that amended claim 61 recites clauses (a)-(d) and (f) that recite aspects of the recited composition and should be given patentable weight. Clause (e) is entitled to patentable weight since it results in a structural difference between the claimed invention and the prior art, and that a cited structure must be "capable of performing the intended use" in order to satisfy such an element. Moreover, clause (c) now recites that the composition "does not comprise animal serum", which is not taught or suggested by Schade (see Remarks, p. 7-8).
Applicant’s arguments have been fully considered and they are persuasive. Therefore, the prior rejection by Schade has been withdrawn. However, as necessitated by amendment, a new ground of rejection has been made by Fei. Specifically, Fei teaches a composition comprising the three components (i.e., human T cells, a BCR-ABL TKI, and a medium) in (a) and (f), the immune cells are modulated by the TKI in (b) and the medium does not comprise animal serum in (c). Clause (d) is directed to an inherent advantage (increased number or ratio of subpopulations of T cells expressing CD62L and/or CCR7) in Fei’s composition, and thus Fei’s composition is capable of performing the intended use for preparing a pharmaceutical composition comprising T cells expressing CD62L and/or CCR7.
New 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 61, 70, 73-74, 76 and 78-82 are rejected under 35 U.S.C. 103 as being unpatentable over Fei et al., (Exp Hematol. 2008;36(10):1297-1308) in view of Themeli et al. (WO 2014/165707A2, also published as US20160009813A1, cited in IDS 04/26/2024).
Claims 61, 70, 73-74, 78 and 82 are anticipated by Fei, thus Fei makes obvious the claims.
Claim 73 is directed to the population of immune cells comprising cells obtained by differentiating stem cells, claim 74 is directed to the stem cells being iPSCs, claim 76 is directed to the immune cells and the stem cells comprising an exogenous nucleic acid encoding a CAR, claim 79 is directed to the T cells comprising CAR-T cells, claim 80 is directed to the immune cells and the modulated immune cells comprising genomically engineered cells comprising an insertion, and claim 81 is directed to the immune cells and the modulated immune cells comprising an exogenous nucleic acid encoding a CAR.
However, Fei is silent on the immune cells obtained by differentiating iPSCs in claims 73 and 74, nor teach the immune cells and the stem cells and the modulated immune cells comprise an insertion of an exogenous nucleic acid encoding a CAR in claims 76 and 79-81.
Themeli teaches a method for generating functional CAR T cells, including memory T cells such as central memory T cells, from pluripotent stem cells (title, abstract, p. 4, line 15, p. 5, line 21, p. 6, lines 17 & 19, p. 44, line 28, p. 94, 2nd para.).
With respect to the immune cells obtained by differentiating iPSCs, Themeli teaches in vitro generation of tumor-targeted human T lymphocytes by differentiating induced pluripotent stem cells in Example 1 (p.78), thus teaches a population of immune cells obtained by differentiating stem cells (claim 73), specifically, iPSCs (claim 74).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition comprising T cells isolated from peripheral blood disclosed by Fei, by substituting the T cells from peripheral blood with the T cells derived from iPSCs taught by Themeli with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so in order to determine if the in vitro effects of tyrosine kinase inhibition applies to T cells from other sources. Furthermore, since Themeli teaches that T cells derived from stem cells are a clinically relevant source of T cells compared to those from peripheral blood [0005-0006], this would have been an obvious population to test the in vitro effects of Fei.
With respect to insertion of an exogenous CAR, Themeli teaches the “clone T-iPSC-1.10 was stably transduced with a lentiviral vector encoding 19-28z, a second-generation CAR” (p.84, lines 5-6), after differentiating into 1928z-T-iPSC-T cells, “all of them expressed the CD19-specific CAR on their surface” (p. 91, line 8), thus teaches the immune cells and the stem cells comprise an exogenous nucleic acid encoding a CAR (claim 76). Since the lentivirus mediates genome integration, Themeli’s T cells comprise genomically engineered cells comprising an insertion (claim 80) and the T cells comprise an exogenous nucleic acid encoding a CAR (claims 79 and 81).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition comprising T cells derived from iPSCs suggested by Fei in view of Themeli, by combining transducing an exogenous nucleic acid encoding a CAR to the iPSCs taught by Themeli with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so in order to determine if the in vitro effects of tyrosine kinase inhibition applies to CAR T cells, since Themeli teaches that CAR T cells are a clinically relevant source of T cells compared to unmodified T cells [0008], this would have been an obvious population to test the in vitro effects of Fei. One of ordinary skill in the art would have understood that the modulated immune cells in the composition of Fei in view of Themeli would have comprised genomically engineered cells comprising an insertion (claim 80) and an exogenous nucleic acid encoding a CAR (claim 81).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 11/04/2025 are acknowledged.
Applicant argues that Schade does not teach or suggest using a medium that does not include animal serum. Themeli does not provide the missing teaching or guidance. While Themeli mention certain methods of differentiation that may be "serum free," there is no mention of a means for inhibiting BCR-ABL tyrosine kinase as being involved in such processes. Accordingly, it was completely unknown from both Schade and Themeli what effect (if any) a means for inhibiting BCR-ABL tyrosine kinase might have had on an human immune cell in a pharmaceutically acceptable medium that does not comprise animal serum. (see Remarks, p. 9).
Applicant’s arguments have been fully considered and they are persuasive. Therefore, the prior rejection over Schade in view of Themeli has been withdrawn. However, as necessitated by amendment, a new ground of rejection has been made over Fei in view of Themeli. Specifically, Fei alone teaches a composition comprising a means for inhibiting BCR-ABL tyrosine kinase, a plurality of human immune cells, and a pharmaceutically acceptable medium that does not comprise animal serum.
Applicant further argues that the present application teaches several technical benefits resulting from the combination of human immune cells with BCR-ABL TKIs cultured in a pharmaceutically acceptable medium. For example, the present application describes results showing that immune cells treated with an illustrative BCR-ABL TKI exhibit several advantageous pharmaceutically relevant attributes, such as reduced T cell exhaustion marker expression (Example 6), continued and increased expansion despite repeated exposure to target cells (Example 8), and improved in vivo tumor clearance efficacy after cryopreservation (Example 9). Considering that none of the cited references disclose culturing human immune cells with a BCR-ABL TKI in a culture medium that does not comprise animal serum, there is no basis in the cited references for reasonably predicting any such results.
Applicant’s arguments have been fully considered but they are not persuasive. As stated supra, Fei teaches a composition comprising a means for inhibiting BCR-ABL tyrosine kinase, a plurality of human immune cells, and a pharmaceutically acceptable medium that does not comprise animal serum. Thus, Fei discloses culturing human immune cells with a BCR-ABL TKI in a culture medium that does not comprise animal serum. Fei teaches the BCR-ABL TKI is effective to produce modulated immune cells upon culturing. Thus, the above advantageous pharmaceutically relevant attributes recognized by Applicants would be in fact inherent features in Fei’s composition.
Furthermore, MPEP 716.02(d), states that unexpected results must be commensurate in scope with the claimed invention. In the instant case, the advantageous pharmaceutically relevant attributes, such as reduced T cell exhaustion marker expression (Example 6), continued and increased expansion despite repeated exposure to target cells (Example 8), and improved in vivo tumor clearance efficacy after cryopreservation (Example 9), were studies performed in culturing human CAR-T cells with a single species of BCR-ABL TKI DCC-2036 in a culture medium that does not comprise animal serum (i.e., a composition comprising a population of human CAR-T cells, DCC-2036, and a pharmaceutically acceptable culture medium that does not comprise animal serum), which is not commensurate in scope with the claimed composition comprising a population of human immune cells, a means for inhibiting BCR-ABL tyrosine kinase, and a pharmaceutical acceptable medium that does not comprise animal serum.
Claims 61, 70, 73-74, 77-78 and 82-83 are rejected under 35 U.S.C. 103 as being unpatentable over Fei et al., (Exp Hematol. 2008;36(10):1297-1308) in view of Chan et al (Cancer Cell. 2011; 19: 556-568. Cited in IDS 04/26/2024).
Claims 61, 70, 73-74, 78 and 82 are anticipated by Fei, thus Fei makes obvious the claims.
Claim 77 is directed to the means for inhibiting BCR-ABL tyrosine kinase comprising DCC-2036, and claim 83 is directed to the composition further comprising DCC-2036.
However, Fei uses dasatinib which is active against all BCR-ABL mutations tested conferring imatinib resistance except one (T315I) (p. 1297, left col), but is silent on the means for inhibiting BCR-ABL tyrosine kinase comprising DCC-2036.
Chan teaches identification of a BCR-ABL1 TKI DCC-2036 that inhibits BCR-ABL tyrosine kinase including the Gatekeeper T315I mutant by conformational control (title, abstract), related to claims 77 and 83. Chan teaches based on structure-based design, DCC-2036, a conformational control inhibitor of ABL1, including the BCR-ABL1 T315I mutant is developed (p.557, right col, line 1). Chan teaches DCC-2036 has stronger inhibition of ABL1 kinases compared to Dasatinib (Tables 1 and 3).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition comprising a BCR-ABL TKI dasatinib disclosed by Fei, by substituting the means for inhibiting BCR-ABL tyrosine kinase with DCC-2036 suggested by Chan with a reasonable expectation of success. Since Fei teaches dasatinib is not active against T315I mutation (p. 1297, left col), and since Chan teaches DCC-2036 inhibits BCR-ABL tyrosine kinase including the T315I mutant and has stronger inhibition on BCR-ABL tyrosine kinases compared to dasatinib (Table 1), one of ordinary skill in the art would have had a reason to make this modification in order to analyze the effect of a broader and more potent BCR-ABL TKI DCC-2036 on activation and proliferation of T cells in vitro.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 11/04/2025 are acknowledged.
Applicant argues that none of the cited references disclose culturing human immune cells with a BCR-ABL TKI in a culture medium that does not comprise animal serum, and there is no basis in the cited references for reasonably predicting the advantageous results of such a combination of features (Remarks, p. 9-10).
Applicant’s arguments have been fully considered and they are persuasive. Therefore, the prior rejection over Schade in view of Chan has been withdrawn. However, as necessitated by amendment, a new ground of rejection has been made over Fei in view of Chan. Specifically, Fei alone teaches a composition comprising a means for inhibiting BCR-ABL tyrosine kinase, a plurality of human immune cells, and a pharmaceutically acceptable medium that does not comprise animal serum, and discloses culturing human immune cells with a BCR-ABL TKI in a culture medium that does not comprise animal serum. Thus, the above advantageous results recognized by Applicants would be in fact inherent features in Fei’s composition.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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/JIANJIAN ZHU/Examiner, Art Unit 1631
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