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 .
Claims Status
The Amendment filed on 27Oct2025 is acknowledged in which claim(s) 1-24 were canceled, and claim(s) 25-73 are new.
Applicant’s election with traverse of Group III and a species election of a CAR T cell wherein the CAR comprises: (1) an antigen binding domain, (2) a CD8a transmembrane domain, and an intracellular T cell activation moiety wherein the T cell activation moiety comprises (a) a 4-1BB (CD137) costimulatory domain, and (b) a ZAP70 signaling domain of SEQ ID NO: 17 (ZAP327), in the reply filed on 20Apr2026 is acknowledged.
Claim(s) 25-43, 54-58, 62, 64, 67-69, and 72-73 is/are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 20Apr2026. The Traversal is on ground(s) that the claim(s) possess a special technical feature that makes a contribution in contrast to the applied prior art of US 20220226374 A1 (hereinafter “US374”). Applicants state that US374 is silent regarding the specific truncated ZAP70 kinase domains (e.g., ZAP300 or ZAP327), and that US374 does not disclose, teach, or suggest the specific ZAP70 signaling domains that provide enhanced T cell persistence and reduced T cell exhaustion as demonstrated in the instant specification. This is not found persuasive because the lack of unity was not based on specific ZAP70 mutants and/or variants of the dependent claims, but rather on the broader claim of a “…signaling domain comprises the ZAP70 kinase domain or a mutant or variant thereof…”, as in instant claim 44, lines 6-7. The lack of unity was based on the common technical feature of Groups III and Group IV, which is based on the CAR construct comprising a ZAP70 kinase domain, which appears to be drawn to a CAR T cell wherein the CAR comprises an antigen recognition moiety, a transmembrane domain, a CD28 or 4-1BB domain, and a ZAP70 kinase domain or a mutant or a variant thereof, as disclosed by US374 [e.g., ¶ 0007, 0023, 0184, 0192-0194]. Applicants further argue that Groups III and IV are related and that search for one group should provide relevant information for another group and thus there is no burden to search all of the claims. This argument is not persuasive because these restriction-related issues are addressed in applications filed under 35 USC 111(a). The analysis used to determine whether the Office may require restriction differs in national stage applications submitted under 35 USC 371 (unity of invention analysis) as compared to national applicated filed under 35 USC 111(a).
The requirement is still deemed proper and therefore made FINAL.
Claim(s) 44-53, 59-61, 63, 65-66, and 70-71 is/are presented for examination on the merits.
Drawings
The drawings are objected to because:
Figs. 2, 14A: text in shaded boxes is unclear.
Figs. 16C, 17B: bar chart shading is too similar to differentiate.
Fig. 18B: not clearly legible.
Figs. 19D-E: unclear which survival plot line is 19bbz vs Ctrl.
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 Interpretation
Claim(s) 47-48 recite(s) “truncated” ZAP70 kinase domain. However, truncation of ZAP70 kinase domain is not defined in the instant specification. UniProt teaches that wild type ZAP70 kinase comprises 619 amino acids [e.g., pg. 1, “Amino Acids”]. Therefore, the broadest reasonable interpretation is considered to be that any ZAP70 kinase domain comprising fewer than 619 amino acids is a “truncated” ZAP70 kinase domain.
Claim(s) 59 recite(s) “wherein the CAR is fused with a chemokine receptor”, but doesn’t define in the claim(s) or the instant specification any specific fusions of CAR and chemokine receptor (e.g., direct fusion to CAR, expressed in the same vector, expressed in the same cell, etcetera). Therefore the broadest reasonable interpretation is considered to be include teachings in the prior art comprising the CAR and an engineered (e.g., not naturally occurring) cytokine receptor.
Claim Objections
Claim(s) 44 is/are objected to because of the following informalities: “wherein the costimulatory signaling domain selected from” is grammatically incorrect. Appropriate correction is required
Claim(s) 49 is/are objected to because of the following informalities: “antibody, an antigen-binding fragment,” in line 2 should be “antibody[[, an]] or antigen-binding fragment thereof,”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
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.
Claim(s) 44-53, 59-60, 63, 65-66, 70-71 is/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.
Claim 44-53, 59, 65-66, recite(s) the limitation "the Zap70 kinase domain" in line 6 of claim 44. There is insufficient antecedent basis for this limitation in the claim. For the purposes of compact prosecution, "the Zap70 kinase domain" is considered to be "a Zap70 kinase domain". This rejection may be overcome by amending claim(s) 44 as described above or to otherwise provide proper antecedent basis. Claim(s) 45-53, 59, and 65-66can overcome this rejection by amending claim(s) 44 as described above.
Claim(s) 44-46, 48-51, 53, 59-60, 63, 65-66, and 70, recite(s) “or a mutant or a variant thereof” in lines 6-7 of claim 44, in line 4 of claim 45, in lines 2-4 of claim 46, in line 5 of claim 48, line2 of claim 52, in claim 70(c); and recite(S) “or a variant thereof” in line 5 of claim 60, rendering the claim(s) indefinite. The instant specification does not define mutant and/or variants of ZAP70 kinase domains, and provides two examples non-limiting examples ZAP70 kinase domains that are not wild-type, including ZAP300 and ZAP327 [e.g., pg. 13, ¶ 2-3; pg. 14, ¶ 1; pg. 15, ¶ 3; pg. 88-90]. Specifically, it is unclear if a “mutant” and/or a “variant” means (1) a ZAP70 kinase domain comprising 99% identity to wild-type (WT) ZAP70; (2) a ZAP70 kinase domain comprising 90% identity to WT ZAP70, (3) a ZAP70 kinase domain comprising 70% similarity identity to WT ZAP70; (4) a ZAP70 kinase domain comprising 40% identity to WT ZAP70; or (5) something else. For the purposes of compact prosecution, any ZAP70 kinase domain known in the art will be considered to apply for “mutant” or “variant” ZAP70 kinase domains. This rejection may be overcome by amending claim(s) 44, 45, 46, 48, 52, 60, and 70 to remove references to “mutant” and/or “variant” ZAP70 kinase domains, or to properly provide a closed definition of such domains.
Claim(s) 45 recites the limitation "the replacement of CD3ζ with" in lines 3-4. There is insufficient antecedent basis for this limitation in the claim. Specifically, claim 45 depends from claim 44, and neither of claims 44-45 state that the signaling domain is CD3ζ, and there cannot be a “replacement” of a signaling domain that is not a comprising part of the instant invention. For the purposes of compact prosecution, the phrase "the replacement of CD3ζ with" is not considered a part of the instant invention. This rejection may be overcome by amending claim 45 to delete reference to "replacement of CD3ζ", or to provide proper antecedent basis.
Claim(s) 46-47 is/are indefinite for reciting “derivatized from” as the exact meaning of the word is not known. The term “derivatized'' is not one, which has a universally accepted meaning in the art nor is it one which has been adequately described in the specification. The primary deficiency in the use of this phrase is the absence of an ascertainable meaning for said term. Some species of ZAP70 kinase domains that are not wild-type are disclosed in the specification, including ZAP300 and ZAP327, but this is not defined as a closed group [e.g., pg. 13, ¶ 2-3; pg. 14, ¶ 1; pg. 15, ¶ 3; pg. 88-90]. Further, the instant specification provides “…derivatization may alter the function of the protein…” [e.g., pg. 55, ¶ 1]. Since it is unclear how ZAP70 is to be derivatized to yield the class of molecules referred to in the claims, a person of skill in the art cannot describe the metes and bounds of a discrete and identifiable class of molecules to these claims. For the purposes of compact prosecution, the phrase “derivatized from” is not considered part of the instant invention. This rejection may be overcome by amending claim(s) 46 to remove references to derivatives. Claim(s) 47 can overcome this rejection by amending claim 46 as described above.
Claim(s) 49 recites a list of antigen recognition moieties comprising elements without a joining word between “mimetic” and “a protein receptor” in line 3, rendering the claim indefinite. Specifically, it is unclear if the antigen binding moiety comprises (1) one of the listed elements; (2) a specific combination of listed elements; (3) any combination of the listed elements; or (4) something else. For the purposes of compact prosecution, the joining word between the listed antigen binding moiety elements is considered to be “or”.
Claim(s) 50 recite(s) “wherein the antigen recognized by the antigen recognition moiety is selected from the group of antigens recognized by scFv consisting of [list of antigens], or any combination thereof” in line(s) 1-4, rendering the claim(s) indefinite. Specifically, it is unclear if the phrase means (1) the antigen recognition moiety is required to comprise an scFv; (2) how one scFv would recognize a combination of the listed antigens (e.g., no indication of why cross-reactivity would be expected for those antigens); (3) if the antigen recognition moiety is monoclonal; (4) if the antigen recognition moiety is multispecific; or (4) something else. For the purposes of compact prosecution, the phrase will be considered to mean “wherein the antigen recognition moiety comprises an scFv and wherein the scFv binds an antigen selected from [list of antigens].”. This rejection may be overcome by amending claim(s) 50 as recited above or to otherwise clearly recite the limitation(s) of the instant invention.
Regarding claims 51, 63, 70, the phrase “(A2-ESO-1, DP4-ESO-1)” is not defined in the terms preceding it. Thus, the phrase “(A2-ESO-1, DP4-ESO-1)” renders the claim indefinite because it is unclear whether the limitation(s) in the parentheses are a part of the claimed invention. See MPEP 2173.05(d). It is unclear if “A2-ESO-1, DP4-ESO-1” is a limitation or merely provided as an example. To promote compact prosecution, the phrase “A2-ESO-1, DP4-ESO-1” is not considered a limitation of the claim(s). This rejection may be overcome by amending claim(s) 51, 63, 70 to delete “(A2-ESO-1, DP4-ESO-1)”.
Regarding claim(s) 59, 63, 70, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(h)(II). It is unclear if the limitation(s) following the phrase are limitation(s) or merely provided as an example. For the purposes of compact prosecution, the limitations following the phrase are not considered part of the claimed invention. This rejection may be overcome by amending claim(s) 59, 63, 70 to remove “optional” limitations and/or the phrase “optionally”.
Claim(s) 70-71 recite(s) 70(a)-(d) without a joining words between 70(c) and 70(d), rendering the claim indefinite. Specifically, it is unclear if claim 70(a)-(d) means the CAR of claim 70 comprises (1) only one of 70(a) – (d); (2) each of 70(a)-(d); or (3) something else. For the purposes of compact prosecution, the joining word between 70(c) and 70(d) is considered to be “or”. This rejection may be overcome by amending claim 70 to include a joining word between 70(c) and 70(d). Claim 71 can overcome this rejection by amending claim 70 as described above.
Claim(s) 53 is/are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: the instant claim(s) is/are lacking clear steps to expressing the CAR for functional activation of immune cells. For the purposes of compact prosecution, any teaching of expressing the CAR of the instant invention in an immune cell will be considered to teach functional activation of immune cells. This rejection may be overcome by amending claim(s) 53 to clearly recite the steps for expression the car for functional activation of immune cells.
Claim Rejections - 35 USC § 112(a) – enablement
Claim(s) 50 is/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a CAR comprising an antigen recognition moiety, does not reasonably provide enablement for any combination of the recited antigen binding fragments of instant claim 50. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation."' (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (A) The nature of the invention; (B) The breadth of the claims; (C) The amount of direction provided by the inventor; (D) The existence of working examples; (E) The state of the prior art; (F) The level of predictability in the art; (G) The quantity of experimentation needed to make or use the invention based on the content of the disclosure and (H) The level of one of ordinary skill. While all of these factors are considered, a sufficient amount for amount for a prima facie case are discussed below.
The nature of the invention
Claim(s) 50 is/are drawn to a CAR comprising an antigen recognition moiety comprising “ScFv fragments, Fv fragments, Fd fragments, Fab fragments, Fab' fragments, F(ab)'2 fragments, VH domains, VL domains, monoclonal antibodies, polyclonal antibodies, or any combination thereof”.
Breadth of the claims
The invention as disclosed in claim(s) 50 is/are readable to 3CDRs, which is effectively half of an antibody binding site, as being sufficient for a functional antibody recognition moiety. Specifically, the claim limitations as written require (I) only one VH domain (e.g., Fd fragment or VH domain) comprising 3 CDRs (e.g., HCDR1-3) or (II) only one VL domain comprising 3 CDRs (e.g., LCDR1-3), which is effectively half an antibody binding site missing either (I) the VL complement (with LCDR1-3) or (II) the VH complement (with HCDR1-3), respectively, to create a full antibody binding site (e.g., 6 CDRs). One of ordinary skill in the art would understand that one cannot use half of an antibody binding domain (e.g., VH only) and reasonably expect to maintain target antigen binding function.
Further, claim(s) 50 is drawn to a mix and match of antibodies and/or antibody antigen binding fragment domains. Specifically, the inventions as disclosed in claim(s) 50 recite(s) “…wherein the antibody, antigen binding fragment, antibody mimetic, a protein receptor or ligand for a specific receptor comprises ScFv fragments, Fv fragments, Fd fragments, Fab fragments, Fab’ fragments, F(ab)’2 fragments, VH domains, VL domains, monoclonal antibodies, polyclonal antibodies, or any combination thereof”. These claims read that one would be able to mix and match any and all antibodies and/or antibody antigen-binding domain fragments listed and arrive at an antibody that binds to a target antigen. One of ordinary skill in the art would understand that to antibodies and/or antibody binding domains, the result must result in one or more complete antigen recognition moiety, with each complete antigen binding domain minimally comprising HCDR1-3 and LCDR1-3 sequences. Briefly, non-limiting examples of non-functional combinations readable to claim 50 include (1) a Fd fragment and a VH (e.g., comprising 2 distinct sets of HCDR1-3 only); and (2) a scFv and a VL domain (e.g., comprising one full 6 CDR set, and half an antigen binding domain comprising LCDR103 only).
The instant disclosure teaches antibody and/or antigen binding fragments thereof (e.g., antigen recognition moieties) are derived from or related to an antibody, which bind to an antigen.
The amount of direction provided by the inventor/the existence of working examples
The examples of the instant disclosure of a CAR comprising an antigen recognition moiety include(s) scFvs that specifically bind to CD19, BCMA, B7-H3, Mesothelin, or HER2 [e.g., pg. 15, ¶ 2; figs. 18A-E, 26A-C; examples 4].
Additionally antibody-derived antigen recognition fragments are readily known in the art and include but are not limited to scFv, Fab, Fv, Fab’, F(ab)’2.
The state of the art/the level of predictability in the art
At the time of filing, antibody functionality of classical antibody antigen binding domains were known to depend on the entire structure, particularly a full complement of six CDRs. It is understood by one of ordinary skill in the art that that mutation to CDRs is unpredictable and that each construct requires function testing.
Sela-Culang, Kunik, and Ofran (Fron. Immuno., Vol. 4, Article 302, Oct. 2013), hereinafter “Sela-Culang”, reviews the structural basis of antibody-antigen recognition in the state of the art. Naturally occurring antibodies have six hypervariable loops are commonly termed complementary determining regions (CDRs) and are widely assumed to be responsible for antigen recognition [e.g., pg. 1, abstract; pg. 3, “The Role of CDRs and their Definition”]. A person of ordinary skill in the art would understand that although the above basics of antibody-antigen binding are known, that the specifics of antibody structure (e.g., within the CDRs) that underlie the antigen recognition are not well characterized [e.g., pg. 1, “The Motivations for…”].
Further, Herold et al. (Nature Scientific Reports, 7:12276, 25 Sep 2017), hereinafter “Herold”, teaches that it should be emphasized that there is no correlation between experimentally determined change in antibody binding affinity and a given mutation and additionally that no such correlation is expected because antigen binding is “affected by each CDR loop differently” and changes thereto “can in principle affect antigen binding affinity in an unpredictable way” [e.g., pg. 14, ¶ 2]. Further, Herold asserts that multiple determinants regulate antigen affinity and the interactions with CDRs are complex [e.g., pg. 14, ¶ 3].
Thus, wherein the antigen binding domain of a CAR comprises an antibody or antigen binding domain fragment thereof (e.g., as in instant claim 50), the full six CDRs of an antibody sequence are required for target antigen recognition and/or binding.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
Based on the instant disclosure and prior art, there is no known method through which one of ordinary skill in the art would have been able to reliably predict which, if any, (1) half of an antigen binding domain fragments (e.g., Fd fragment, VH domain, VL domain); and/or (2) combinations of antigen binding domain fragments not taught in the prior (e.g., a Fd fragment and a VH (e.g., comprising 2 distinct sets of HCDR1-3 only), would result in an antigen recognition moiety (e.g., antigen binding domain) that retains the ability to bind target antigen (e.g., CD19). Therefore, in order to practice the invention as claimed, one of ordinary skill in the art would have to perform undue experimentation to create and test each and every possible combination of the recited antigen recognition fragments for each and every target antigen. Applicant is enabled for antigen binding fragments (e.g., antigen recognition moieties) known in the art to be functional for binding to a target antigen.
Conclusion
In view of the Wands factors as discussed above, one of ordinary skill in the art would have to engage in undue experimentation to practice the full scope of the instant claimed invention. As such, instant claim(s) 50 was/were determined to not meet the scope of enablement requirement of 35 USC § 112(a).
Enablement can be met by amending claim(s) 50 to recite only those antigen recognition moieties known in the art to bind a target antigen.
Claim Rejections - 35 USC § 112(a) – written description
Claim(s) 44-53, 59-61, 63, 65-66, and 70-71 is/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claimed Invention
Claim(s) 44-53, 59-61, 63, 65-66, 70-71, are drawn to a CAR comprising a derivatized, mutant, and/or variant ZAP70 kinase domain comprising a functional ZAP70 kinase domain.
Breadth of Claims
The invention as disclosed in claim(s) 44 (and dependent claim(s) 45-53, 59, 65-66) recite(s) “…the signaling domain comprises the ZAP70 kinase domain or a mutant or a variant thereof…”; claim(s) 46 recite(s) “…the CAR comprises the ZAP70 kinase domain derivatized from a functional wild type ZAP70 or a mutant or a variant thereof, wherein the ZAP70 kinase domain derivatized from a functional wild type ZAP70 or a mutant or a variant thereof further comprises a functional ZAP70 kinase domain…”; claim(s) 48 recite(s) “…a mutant of a variant thereof wherein the mutant or variant is a truncated biologically active fragment containing a functional ZAP70 kinase domain…”; . claim(s) 60 (and dependent claim(s) 61, 63) recite(s) “…a ZAP70 kinase domain or a variant thereof…”; and . claim(s) 70 (and dependent claim 71) recite(s) “…a ZAP70 kinase domain or a mutant or a variant thereof…”. The instant specification teaches the instant invention comprises a functional ZAP70 kinase domain (e.g., critical part of the instant invention) [e.g., ¶ pgs. 13-15; figs. 18A-E]. One of ordinary skill in the art would understand that the protein sequence, and/or proper folding/assembly are responsible for the function of enzymes and functional domains thereof (e.g., ZAP70 kinase domains), including acting as a signaling domain in a CAR construct. The claim(s) do/does not disclose the structure(s) (e.g., amino acid sequence) associated with the claimed function. The instant disclosure does not provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision all possible ZAP70 protein sequence derivatives, mutants, and/or variants, such that the obtained structure would result in the claimed functions.
Scope of Disclosed Species
The ZAP70 kinase domains in the Applicant disclosure including (1) wild type ZAP70 kinase domain, (2) ZAP300 kinase domain, and (3) ZAP327 kinase domain, represents the three ZAP70 kinase domain species that the applicant was in possession of at the time of filing [e.g., pg. 13, ¶ 2-3; pg. 14, ¶ 1; pg. 15, ¶ 3; pg. 88-90], but the specification does not define if these species are considered derivatives, mutants, and/or variants.
State of the Prior Art
At the time of filing, the functionality of enzymes and/or domains thereof (e.g., ZAP70 kinase domains) was/were known to depend on the protein sequence, proper folding, and PTMs. Further, The instant disclosure acknowledges that “…derivatization may alter the function of the protein…” [e.g., pg. 55, ¶ 1], and therefore require function testing. No structure-activity relationship was found in the prior art, nor provided in the instant specification that would allow for prediction of all of the possible derivatives, mutants, and/or variants of ZAP70 kinase domain that retain function/signaling activity.
The instant disclosure and the prior art do not teach a known structure activity relationship for ZAP70 kinase domains that would allow prediction of all of the possible ZAP70 kinase domain derivatives, mutants, and/or variants of ZAP70 kinase domains that would retain the required function(s).
Conclusion
As indicated by the applicant, derivatization of ZAP70 may alter the function of the protein, and therefore would require function testing. Written description can be met if the claims recite the minimal structure that is needed to perform the function(s). Above, the instant disclosure and/or prior art indicate(s) that the specific ZAP70 kinase domain derivatives, mutants, and/or variants thereof (e.g., sequence(s) and/or names known in the art) are the minimum structure required to perform the recited function(s). Specifically, Applicant claim(s) 44, 60, 70 would need to recite (1) the ZAP70 kinase domain derivative name(s) (e.g., if known in the art at the time of filing), and/or (2) the amino acid sequence of each and every ZAP70 kinase domain claimed as part of the instant invention. Dependent claim(s) 45-53, 59, 31, 63, 65-66, and 71 can overcome this rejection by amending claim(s) 44, 60, and 70 as recited above. Applicant is advised that amending claim(s) 44, 60, and 70 as recited above may result in a lack of antecedent basis for limitations in dependent claim(s) (e.g., derivatives, mutants, variants thereof), and therefore Applicant is advised to remove such terms to avoid new rejection(s).
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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 44-53, 60-61, 63, 65-66, 70-71 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2019/0023761 A1 (hereinafter “US761”).
Regarding instant claim(s) 44-52, 60-61, 63, 65, 70-71, US761 teaches a pharmaceutical composition comprising CAR T cells comprising a CAR comprising an anti-CD19 scFv (e.g., antigen recognition moiety), a transmembrane domain, a 4-1BB costimulatory domain, and an intracellular ZAP70 kinase domain [e.g., title, abstract; ¶ 0010; 0055-0056, 0204, 0236, 0238, 0413; fig. 5(b)]. US761 further teaches the ZAP70 domain comprises SEQ ID NO: 26 (e.g., truncated, see claim interpretations) [e.g., ¶ 0269-0270], which is the same as instant elected ZAP327 kinase domain (SEQ ID NO: 17; see alignment below). . US761 further teaches that pharmaceutical compositions further comprises a pharmaceutically acceptable carrier [e.g., ¶ 0463] and is useful in treating cancer (e.g., a therapeutically effective amount of CAR T cells) [e.g., ¶ 0464-0469].
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200
400
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Greyscale
Alignment of ZAP327 (SEQ ID NO: 17) with US761 (Human ZAP70 protein kinase domain, SEQ ID 26):
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498
617
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Greyscale
Regarding instant claim(s) 53, 66, US761 further teaches transfection or transduction of a T cell with a vector comprising the CAR construct (e.g., a method of expressing the CAR construct) [e.g., ¶ 0426-0432]. US761 teaches the construct results in stimulatory T cell (e.g., T cells, CD4+ T cells, CD8+ T cells) activating signals [e.g., ¶ 0276-0287; tbl. 1; fig. 9]. US761 further teaches that CAR constructs containing ZAP70 kinase domain(s) result in increased IFNy production [e.g., ¶ 0485]. IFNy activates macrophages, as evidenced by Müller [e.g., title, abstract].
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) 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0023761 A1 (hereinafter “US761”), as applied to claim(s) 44 above, and further in view of Tokarew et al. (British Journal of Cancer (2019) 120:26–37; hereinafter “Tokarew”).
The teachings of US761 as recited above apply for claim 44.
US761 does not expressly teach that the CAR T cell further comprises a chemokine receptor.
Regarding instant claim(s) 59, Tokarew teaches further engineering CAR T cells to comprise expression of a chemokine receptor (e.g., “fused”, see claim interpretation above) to increase CAR T cell recruitment (e.g., trafficking) [e.g., pg. 29].
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to combine the pharmaceutical composition comprising a CD19 directed CAR comprising transmembrane domain, a 4-1BB domain, and a ZAP70 domain as taught by US761, with the CAR T cell further comprising a chemokine receptor as taught by Tokarew, to arrive at a pharmaceutical composition comprising a CD19 directed CAR comprising transmembrane domain, a 4-1BB domain, and a ZAP70 domain, further comprising a chemokine receptor (e.g., fused, see claim interpretation above). A PHOSITA would have been motivated to combine the pharmaceutical composition comprising a CD19 directed CAR comprising transmembrane domain, a 4-1BB domain, and a ZAP70 domain as taught by US761 with the chemokine receptor as taught by Tokarew, because Tokarew teaches engineering CAR T cells to further express chemokine receptors is known and employed in the art to increase CAR T cell trafficking. There would have been a reasonable expectation of success for a PHOSITA to combine the pharmaceutical composition comprising a CD19 directed CAR comprising transmembrane domain, a 4-1BB domain, and a ZAP70 domain as taught by US761 with the chemokine receptor as taught by Tokarew, because US761 teaches the composition and CAR T cells, and Tokarew teaches engineering CAR T cells to further express chemokine receptors is known and employed in the art to increase CAR T cell trafficking. This rationale aligns with the principle of applying a known technique to a known method to yield predictable results, supporting a conclusion of obviousness (see MPEP § 2143).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are currently allowed.
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/AMY M. CHATTIN/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
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