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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/27/2026 has been entered.
Applicant’s amendment, filed on 2/27/2026, is acknowledged.
Claims 1-50, 55, 60-67, and 69 are cancelled.
Claims 51-54, 56, 59, 68, 70, and 71 are currently pending and are under examination as reading on a chimeric polypeptide comprising an anti-CD19 ECD, a CD28 hinge domain, a CD28 TMD, a CD3ζ ICD, and a 4-1BB co-stimulatory domain.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/02/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner in its entirety.
Claim Rejections - 35 USC § 112
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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 51-54, 56-59, 68, 70, and 71 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 claims 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 inventors, at the time the application was filed, had possession of the claimed invention.
Claims 51-54, 56-59, 68, 70 recite a broad genus of scFv structures with little to no structure and the function of “binds to CD19”.
Claims 51-54, 56-59, 68, 70, and 71 additionally recite a broad genus of hinge domains structures with no recite structure (i.e. amino acid sequence) and the function of “CD28 hinge domain”.
Regarding the broadly claimed genus of CAR ECD scFv structures with the function of “binds to CD19” (claims 51-54, 56-59, 68, and 70):
The claims are rejected under 35 U.S.C. 112(a) written description for the same reasons discussed in the Office Action mailed on 10/09/2025.
Applicant’s arguments, filed 2/27/2026, have been fully considered, but have been found to be not convincing.
Applicant argues that the specification provides sufficient written description support of such a broadly claimed genus of structures with no recited structure and the function of “binds to CD19”, and gives examples of functional anti-CD19 scFv structures found in the instant specification (Remarks pg. 6).
This has been found to be not convincing for the same reasons set forth in the Office Action mailed on 10/09/2025. Briefly, while the instant specification discloses specific scFv structures, defined by their amino acid sequences, with the function of “binds to CD19”, the instant specification neither provides a sufficient representative species to represent such as broadly claimed genus of scFv structures. Furthermore, the instant specification not only fails to disclose structural features common to scFvs capable of binding specific targets, it also fails to disclose a way to distinguish those scFvs capable of binding from scFvs incapable of binding those targets. Thus, the specification failed to adequately describe a broad genus of generic binding elements or a narrower genus of scFvs based on the shared structure between all anti-CD19 scFvs under 35 U.S.C. 112(a) WD.
To overcome this rejection, it is recommended to amend instant claim 51 to recite disclosed structures of scFvs with the function of “binds to CD19”, i.e., SEQ ID NO: 3, 17, and 31 (the scFv structures recite in instant claim 71).
Regarding the broadly claimed genus of CAR hinge domains with the function of “CD28 hinge domain” (claims 51-54, 56-59, 68, 70, and 71):
The claims recite a broad genus of hinge domain structures with no recited structure (i.e., amino acid sequence) and the function of “CD28 hinge domain”, which encompasses any polypeptide sequence with this function.
The specification discloses (¶[007]): “…it has been determined that incorporation of a CD28 hinge domain in a polypeptide or CAR that either contains no costimulatory domain or contains a costimulatory domain not derived from CD28 could result in surprisingly enhanced functionality.” The instant specification further discloses that CAR-T cells comprising anti-CD19 CARs with the CD28 hinge domain were more potent at reducing tumor progression when compared to a CAR without the CD28 hinge domain (Examples 1 and 2, Fig. 2A):
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However, the specification fails to provide adequate written description support for a genus of polypeptides with no recited structure having the desired functional properties required to practice the claimed function of “CD28 hinge domain”.
The claims are not supported by a description that satisfies 35 U.S.C. § 112(a) or 35 U.S.C. § 112, first paragraph. "[T]he test for sufficiency [of the written description] is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Phanns., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane).
A "sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Id. at 1350. "[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials." Id.
"[F]unctional claim language can meet the written description requirement when the art has established a correlation between structure and function." Id. "But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species." Id.
"A sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
The specification discloses five specific examples of CD28 hinge domain sequences, which are SEQ ID NO: 5, 19, 33, 45, and 59 (¶[0088]).
With respect to representative number of species, see AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014). Also, see MPEP 2163 Il(A)(3)(a))(ii):
A representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See Abb Vie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.").
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
In the instant case, the application is claiming any CD28 hinge domain structure with the function of “CD28 hinge domain” that also increases CAR-T potency. However, the instant specification discloses only 5 polypeptide structures with this function. These five structures do not represent the broad genus of polypeptides of any sequence and length that are encompassed by the claims.
Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed antigen binding constructs to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function.
Given the broadly claimed class of hinge domains, and in the absence of sufficient disclosure of relevant identifying characteristics for the broadly claimed class of hinge domains, the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014), MPEP 2163.
The specification at best describes plan for making hinge domains that have the recited function “CD28 hinge domain”, and then identifying those that satisfy the claim limitations, but a mere “wish or plan” for obtaining claimed invention is not sufficient. Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011).
Therefore, there is inadequate written description information in the instant specification to support a broadly claimed genus of polypeptide hinge domains with the function of “CD28 hinge domain”. It is recommended to amend instant claim 51 to recite specific hinge domain sequences with this function (i.e., SEQ ID NO: 5, 19, 33, 45, and 5) to resolve this issue.
Possession is not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus may be achieved by means of a recitation of a representative number of anti-TMPRSS6 antibodies or antigen binding fragments thereof falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406.
Claims 51-54, 56-59, 68, and 70 do not meet the requirements of 35 U.S.C. 112(a) for written description.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
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.
Claims 51-54 and 56-59 are rejected under 35 U.S.C. 103 as being unpatentable over Milone et al. (Mol Ther. 2009 Aug;17(8):1453-64. doi: 10.1038/mt.2009.83. Epub 2009 Apr 21, in Office Action mailed 10/29/2025) in view of Alabanza et al. (Mol Ther. 2017 Nov 1;25(11):2452-2465. doi: 10.1016/j.ymthe.2017.07.013. Epub 2017 Jul 27, in Office Action mailed 10/29/2025), as evidenced by Oldham et al. (Expert Opin Biol Ther. 2017 Aug;17(8):961-978. doi: 10.1080/14712598.2017.1339687. Epub 2017 Jun 16).
Milone et al. teaches a chimeric antigen receptor (i.e., “a chimeric polypeptide”) comprising, from the N-terminus to the C-terminus, an anti-CD19 scFv (i.e., “an scFv that binds CD19”), a CD8α hinge and TM domain, and an intracellular domain comprising a 4-1BB co-stimulatory domain and a CD3ζ domain (Figure 1, see annotated and cropped version below):
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Note that the “hCD8α hinge” region includes a TM domain, as can be seen in Figure 1 (the black lines that the arrow is pointing to denotes the plasma membrane of a cell). Also note that the CAR taught by Milone et al. does not comprise a co-stimulatory domain from CD28. Milone et al. additionally teaches CAR T-cells comprising this CAR in a pharmaceutically acceptable carrier for use to effectively treat a mouse model of ALL (“T cells were injected into animals 9-21 days following ALL injection…”, “Mouse xenograft studies” section; also see Figure 5). The CD19 antigen that the CARs target is therefore a tumor-associated antigen (i.e., the limitation of instant claim 54).
Milone et al. does not teach a CAR comprising CD28 hinge and TM domains (i.e., instant claim 51).
Alabanza et al. in the same field of endeavor, teaches anti-CD19 CARs have different functions based on whether or not the CARs contain hinge and TM domains from CD8α and C28 (Abstract). Alabanza et al. teaches that both chimeric antigen receptors were effective in eliminating CD19 expressing tumors in vivo (“Human T Cells Expressing Hu19-CD828Z and Hu19-28Z Can Eliminate Tumors of CD19+ Cells In Vivo” section; Figure 6).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the invention, to have modified the CAR taught by Milone et al. in view of Alabanza et al. to replace the CD8α hinge and TM domains of the CAR taught by Milone et al. with those from CD28 with a reasonable expectation of success, as both references teach anti-CD19 CAR engineering that can apply to any of the taught CARs. One would have been motivated to make this change for the purposes of eliminating CD19 expressing tumors in vivo.
Additionally, regarding replacing the CD8α hinge domain taught by Milone et al. with the CD28 hinge domain from Alabanza et al., it would have been obvious to have replaced these two art-recognized equivalent structures that function as a functional CAR hinge domain. The references teaches that both of these hinge domains are functional hinge domains that can be used in anti-CD19 CARs. See Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980) (The mere fact that phthalocyanine and selenium function as equivalent photoconductors in the claimed environment was not sufficient to establish that one would have been obvious over the other. However, there was evidence that both phthalocyanine and selenium were known photoconductors in the art of electrophotography. "This, in our view, presents strong evidence of obviousness in substituting one for the other in an electrophotographic environment as a photoconductor." 209 USPQ at 759.) Also see MPEP § 2143(I)(B).
Furthermore, Oldham et al. is provided as an evidentiary reference to demonstrate that both CD8 and CD28 hinge domains are commonly used in chimeric antigen receptors in the prior art (Fig. 1A, cropped below):
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Oldham et al. further teaches that both these hinge domains are commonly used in CARs (Section 2.4.3): “[w]hile both CD8α and CD28 hinges have been broadly used in CAR clinical trials, they have not been directly compared clinically. Since many other factors vary between trials, it is quite difficult to determine if one hinge is truly superior.”
Regarding instant claim 56, one with ordinary skill in the art would expect an anti-C19 CAR is expected to bind to CD19 whether it is expressed at low density or not. For example, Milone et al. teaches anti-CD19 binding CARs (Fig. 1).
Applicant’s arguments, filed on 2/27/2026, have been fully considered, but have been found to be not convincing. Applicant argues: A) Milone et al. failed to teach every element of the claimed invention; and B) Alabanza et al. fails to remedy the deficiencies of Milone et al.
Regarding A) Milone et al. failed to teach every element of the claimed invention:
Applicant argues that Milone et al. does not teach every element (Remarks pg. 12): “…Milone clearly failed to teach any car comprising a CD28 hinge domain.”, and does not provide rationale to combine this reference with Alabanza et al. (Remarks pg. 12): “…Milone neither teaches nor suggests any rationale or methodology for modifying the disclosed CAR to incorporate a different hinge domain.”
This has been found to be not persuasive. The 35 U.S.C. § 103 supra rejection relies on the combination of all of the cited references. Milone et al. and Alabanza et al. in combination teach each of the elements of the instant application, as discussed supra. Additionally, while neither Milone et al. nor Alabanza et al. do not explicitly recite a rationale to combine the references or swap the hinge domains between the two anti-CD19 CARs, MPEP § 2144(I) states:
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992); see also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); Ex parte Clapp, 227 USPQ 972 (Bd. Pat. App. & Inter. 1985) (examiner must present convincing line of reasoning supporting rejection); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning).
In the instant case, the rational to combine the references comes from substitution of the two known elements of CAR hinge domains. See MPEP § 2143(I)(B):
To reject a claim based on this rationale, Office personnel must resolve the Graham factual inquiries. Then, Office personnel must articulate the following:
a finding that the prior art contained a device (method, product, etc.) which differed from the claimed device by the substitution of some components (step, element, etc.) with other components;
a finding that the substituted components and their functions were known in the art;
a finding that one of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable; and
whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness.
The anti-CD19 CARs taught by Milone et al. and Alabanza et al. contained different hinge components. Additionally, Milone et al. and Alabanza et al. teach that their respective hinge domains function as CAR hinge domains, and Oldham et al. further teaches CD8 and CD28 hinge domains are commonly used in CARs. Therefore, as discussed supra, one with ordinary skill in the art could have substituted these known hinge domain elements with a reasonable expectation of success using basic molecular biology/cloning techniques that are common in the art.
Additionally, in response to applicant’s arguments against the references individually, one cannot show non-obviousness by attacking references individually where the rejections are based on combination of references. See MPEP 2145. Contrary to applicant’s arguments against the references individually, note that One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to be an argument that attacks the reference(s) individually. Where an applicant’s reply establishes that each of the applied references fails to teach a limitation and addresses the combined teachings and/or suggestions of the applied prior art, the reply as a whole does not attack the references individually as the phrase is used in Keller and reliance on Keller would not be appropriate. This is because "[T]he test for obviousness is what the combined teachings of the references would have suggested to [a PHOSITA]." In re Mouttet, 686 F.3d 1322, 1333, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012). See MPEP 2145 IV.
Regarding B) Alabanza et al. fails to remedy the deficiencies of Milone et al.:
Applicant argues (Remarks pg. 13): “…Alabanza expressly details multiple well-supported rationales demonstrating that anti-CD19 CARs containing a CD8α hinge domain confer significant clinical advantages over anti-CD19 CARs containing a CD28 hinge domain.” Applicant further argues that (Remarks pg. 14): “…Alabanza repeatedly stated that CARs containing CD8α hinge/TM domains are clinically advantageous compared to CARs containing CD28 hinge/TM domains.” Applicant cites Alabanza et al. teaching that CARs containing a CD8α hinge/TM domain produced less cytokines that one with CD28 hinge/TM domains. Applicant further argues (Remarks pg. 15): “…the most important finding of their studies is that the reduced cytokine production by Hu19-CD828Z-expressing T cells compared with HU19-28Z-expressing T cells would be clinically advantageous…”
This has been found to be not persuasive. Applicant is relying on the teachings of Alabanza et al. to argue clinical advantages of a CAR with a CD8α hinge/TM domain compared to one with a CD28 hinge/TM domain. To evaluate the evidence that Applicants are relying upon to support the claim of a clinical advantage, the Alabanza et al. reference will be relied upon in its entirety.
Alabanza et al. states that there are potential clinical advantages of a CAR with a CD8α hinge/TM domain (Abstract): “…[i]n anti-CD19 CARs with CD28 costimulatory moieties, lower levels of inflammatory cytokine production and AICD are potential clinical advantages of CD8a hinge and transmembrane domains over CD28 hinge and transmembrane domains.”
Alabanza et al. focused on testing two different CARs, Hu19-CD828Z (with the CD8α hinge/TM domains) and Hu19-28Z (with the CD28 hinge/TM domains; Fig. 1A):
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T-cells expressing both constructs were tested in vitro for CD19 specific activation. When compared to T-cells express Hu19-28Z, Hu19-CD828Z expressing T-cells has less levels of CD8 T-cell degranulation (Fig. 2C), lower levels of IFNγ and TNFα release (Fig. 2E and F), similar proliferation levels (Fig. 4D), and lower levels of IL-2 release (Fig. 4E).
Alabanza et al. remarked on the lack of differences in proliferation rates (pg. 2461, Col. 1, ¶2): “[t]here was not a statistically significant difference in proliferation as measured by CFSE dilution (Figure 4C) or increase in T cell number (Figure 4D) when Hu19-CD828Z CAR T cells were compared with Hu19-28Z CAR T cells. Because of the lower levels of AICD in Hu19-CD828Z CAR T cells, these findings might be somewhat unexpected. These results could be due to the much higher level of IL-2 production by Hu19-28Z CAR T cells (Figure 4E). This high level of IL-2 production by Hu19-28Z CAR T cells might be one factor promoting in vitro proliferation by Hu19-28Z CAR T cells, while other factors such as high levels of AICD might limit the increase in the number of T cells expressing this CAR. IL-2 production might be a particularly important factor in vitro when no exogenous cytokines were added to the culture media as was the case in our proliferation experiments.”
Alabanza et al. examined T-cells expressing both constructs in vivo as well, in a mouse NALM xenograft model (Fig. 6E and F). T-cells expressing both constructs had similar levels in tumor volume reduction (Fig. 6E):
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T-cells expressing both constructs also exhibited increased survival times in mice with tumors with animals treated with T-cells expressing Hu19-28Z having greater percent survival after 50 days, although the p-value for this difference was above the set value of 0.1 for statistical significance (Fig. 6F):
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Alabanza et al. further remarks on the goal of the study and selection of CARs for further study (pg. 2461, Col. 2, ¶2 and 3): “…[d]espite the reduced cytokine production of T cells expressing Hu19-CD828Z versus T cells expressing Hu19-28Z, T cells expressing Hu19-CD828Z can eliminate malignant cells from mice. Our goal is to find a CAR that has the best efficacy to toxicity ratio in humans. Because toxicity is such a significant clinical problem with CAR T cell therapies, it is possible that the better overall CAR for clinical use might be a CAR that is associated with less toxic cytokine release even if this CAR has slightly less anti-malignancy activity in NSG mice… Hu19-CD828Z was modestly inferior to Hu19-28Z at eliminating disseminated leukemia (Figures S8 and S9). We observed no difference in toxicity in mice receiving the T cells expressing the different CARs…”
Alabanza et al. studies the differences between anti-CD19 CARs with CD8α hinge/TM domains and CD28 hinge/TM domains, and found that while T-cells expressing the Hu19-CD28Z CAR with the CD28 hinge/TM domains were more efficacious as eliminating tumors in vivo, the Hu19-CD828Z had less cytokine release. Alabanza et al. states that the Hu19-CD828Z was chosen for further study for its potential reduction in toxic side effects, and Alabanza et al. did not ever test the two CARs for a clinical advantage over each other. In fact, while Hu19-CD828Z may have a “clinical advantage” in one respect with a reduction in cytokine release and therefore a potential reduction in T-cell exhaustion, one with ordinary skill in the art would appreciate that Hu19-CD28Z may have a clinical advantage in another respect (i.e., increased potency at reducing tumor progression).
Additionally, Oldham et al. reviews the functions of hinge domains, including CD28 hinge domains, that are used in CARs and CAR-T cells (Section 2.4.3): “[a]nother well-used and validated hinge domain is derived from CD28. This hinge domain is often combined with the CD28 TM domain and the CD28 costimulatory domain. While both CD8α and CD28 hinges have been broadly used in CAR clinical trials, they have not been directly compared clinically. Since many other factors vary between trials, it is quite difficult to determine if one hinge is truly superior.” Therefore, one with ordinary skill in the art would appreciate that the prior art does not teach a clinical advantage between CARs with a CD28 hinge domain vs a CD8 hinge domain.
A prior art reference may be considered to teach away when "a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken by the applicant." In re Gurley, 27 F.3d 551, 553, 31 USPQ2d 1130, 1131 (Fed. Cir. 1994). General skepticism of those in the art -- not amounting to teaching away -- is also "relevant and persuasive evidence" of nonobviousness. Gillette Co. v. S.C. Johnson & Son, Inc., 919 F.2d 720, 726, 16 USPQ2d 1923, 1929 (Fed. Cir. 1990). In effect, "teaching away" is a more pointed and probative form of skepticism expressed in the prior art. In any case, the presence of either of these indicia gives insight into the question of obviousness.
Here, in contrast to applicant’s assertions of teaching away by the prior art because Alabanza et al. indicate an anti-CD19 CAR with a CD8 hinge domain instead of a CD28 hinge domain may have less potentially harmful cytokine production and AICD levels and is therefore “clinically advantageous”, however Alabanza et al. further teaches that an anti-CD19 CAR with a CD28 hinge domain has greater anti-tumor potency and can also therefore be “clinically advantageous”. Additionally, there is no discouragement nor skepticism in the prior art for use of an anti-CD19 CAR comprising a CD28 hinge domain (for example, a direct comparison of CAR-T cells expressing each construct demonstrating that the CAR with this CD28 hinge domain does not lead to tumor regression in vivo when directly compared to the CAR with a CD8α hinge domain), particularly in light of Alabanza et al. teaching that both anti-CD19 CARs were effective in eliminating anti-CD19 tumors in vivo (Alabanza et al., Figure 6). Additionally, Alabanza et al. teaching a preferred anti-CD19 CAR embodiment, and using this preferred embodiment for testing in a clinical trial, does not constitute teaching away due to a clinical advantage.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 68 and 70 are rejected under 35 U.S.C. 103 as being unpatentable over Milone et al. (supra) in view of Alabanza et al. (supra), as evidenced by Oldham et al. (supra), as applied to claims 51-54 and 56-59 above, and further in view of Delaney et al. (WO2015066551, in Office Action mailed on 10/29/2025).
The teachings of Milone et al. in view of Alabanza et al., as evidenced by Oldham et al. are discussed supra. Milone et al. in view of Alabanza et al., as evidence by Oldham et al. do not teach explicitly teach pharmaceutical compositions comprising the CAR and an acceptable carrier, or kits comprising the CAR (instant claims 68 and 70).
Delaney et al., in the same field of endeavor, teaches pharmaceutical compositions comprising cells comprising CARs and an acceptable carrier such as physiological saline (i.e., instant claim 68; ¶[0163] and claims 72-74). These compositions are useful for administration of the cells into a subject (¶[0153]).
Delaney et al. additionally teaches kits comprising cells comprising pharmaceutical compositions of CART-cells (¶[0173] and claims 80-82). Delaney et al. teaches that the kits can also comprise useful information such as instruction for proper use, proper disposal methods, and the like (¶[0173]).
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant application, to have modified the combined teachings of Milone et al. and Alabanza et al., as evidenced by Oldham et al., further in view of Delaney eta l. to formulate the CAR or CAR-T cells into pharmaceutical compositions and/or package the CAR or CAR-T cells into kits with a reasonable expectations of success, as Delaney teaches such compositions and kits for CAR applications. One would have been motivated to make this change for the purposes of formulating a pharmaceutical composition for administration to a subject and/or providing useful information such as instructions for use and disposal methods in a kit along with the pharmaceutical composition, as taught by Delaney et al.
Applicant's arguments, filed 2/27/2026, have been fully considered, but have been found to be not persuasive.
Applicant argues that the combined teachings of Milone et al. and Alabanza et al. do not teach the limitations of instant claim 51, and Delaney et al. does not cure this deficiency. However, these arguments were found to be unpersuasive for the reasons discussed supra.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim 71 is rejected under 35 U.S.C. 103 as being unpatentable over Milone et al. (supra) in view of Alabanza et al. (supra), as evidenced by Oldham et al. (supra), as applied to claims 51-54 and 56-59 above, and further in view of Jensen (U.S. Patent 9,447,194, in Office Action mailed on 10/29/2025).
The teachings of Milone et al. in view of Alabanza et al., as evidenced by Oldham et al. are discussed supra. Milone et al. in view of Alabanza et al., as evidence by Oldham et al. do not explicitly teach an anti-CD19 CAR comprising an anti-CD19 scFv comprising SEQ ID NO: 3 (i.e., the limitations of instant claim 71).
Jensen teaches chimeric antigen receptors (entire document) comprising anti-CD19 scFvs (Figure 2), including a CAR comprising SEQ ID NO: 9, which comprises an anti-CD19 scFv that is 100% identical to instant SEQ ID NO: 3. Jensen further teaches that cells expressing these CARs successfully bound to and lysed target cells expressing CD19 (Example 6).
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant invention, to have modified the combined teachings of Milone et al. and Alabanza et al., as evidenced by Oldham et al., further in view of Jensen to make and anti-CD19 CAR with an anti-CD19 scFv comprising instant SEQ ID NO: 3 with a reasonable expectation of success, as Jensen teaches CARs with an anti-CD19 scFv comprising instant SEQ ID NO: 3. One with ordinary skill in the art would appreciate this anti-CD19 scFv can be applied to other CARs such as the one taught by the combined teachings of Milone et al. and Alabanza et al. One would have been motivated to make the change for the purposes of making CARs comprising a functional anti-CD 19 scFv to allow the engineered CARs to successfully bind and lyse CD 19-expressing target cells.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 51-54, 56, 57, 68, and 71 are rejected under 35 U.S.C. 103 as being unpatentable over Abbot et al. (U.S. PGPub 20150307623) in view of Jensen (supra).
Abbot et al. teaches polypeptides (claim 1), including chimeric antigen receptors (claim 42), comprising, from N to C terminus (¶[0032]): “…(i) an antigen-binding domain (e.g., an antigen binding domain that binds an antigen on a tumor cell, e.g., an antigen on a tumor cell described above); (ii) a CD28 hinge polypeptide sequence; (iii) a CTLA4 or PD-1 transmembrane domain; (iv) a 4-1BB costimulatory domain; and (v) a CD3ζ intracellular signaling domain.”
Abbot et al. further teaches that the antigen binding domain binds to a tumor-specific antigen (claim 20), including CD19 (claim 34). Abbot et al. further teaches the extracellular domains comprising scFvs (claim 19).
Abbot et al. does not teach CARs comprising an anti-CD19 scFv comprising instant sequence of SEQ ID NO: 3 (i.e., the limitations of instant claims 1 and 71).
Jensen, in the same field of endeavor, teaches chimeric antigen receptors (entire document) comprising anti-CD19 scFvs (Figure 2), including a CAR comprising SEQ ID NO: 9, which comprises an anti-CD19 scFv that is 100% identical to instant SEQ ID NO: 3. Jensen further teaches that cells expressing these CARs successfully bound to and lysed target cells expressing CD19 (Example 6).
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant invention, to have modified the teachings of Abbot et al. in view of Jensen to use the anti-CD19 scFv sequence (i.e., instant SEQ ID NO: 3) taught by Jensen in the CAR taught by Abbot et al. with a reasonable expectation of success, as Jensen teaches CARs with an anti-CD19 scFv comprising instant SEQ ID NO: 3. One with ordinary skill in the art would appreciate this anti-CD19 scFv can be applied to other CARs such as the one taught by Abbot et al. One would have been motivated to make the change for the purposes of making CARs comprising a functional anti-CD 19 scFv to allow the engineered CARs to successfully bind and lyse CD 19-expressing target cells.
The anti-CD19 CAR taught by the combined references of Abbot et al. in view of Jensen would yield a CAR comprising, from N-C: the anti-CD19 scFv of instant SEQ ID NO: 3, a CD28 hinge, a TM domain, a 4-1BB co-stimulatory domain, and a CD3ζ ICD, meeting the limitations of instant claims 51-54, 57, and 71.
Regarding instant claim 56, one with ordinary skill in the art would expect an anti-C19 CAR is expected to bind to CD19 whether it is expressed at low density or not. For example, Milone et al. teaches anti-CD19 binding CARs (Fig. 1).
Regarding claim 68, Abbot et al. teaches pharmaceutical compositions comprising the CAR and an acceptable carrier (¶[0153]), meeting the claim limitations.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 58 and 59 is rejected under 35 U.S.C. 103 as being unpatentable over Abbot et al. (supra) in view of Jensen (supra), as applied to claims 51-54, 56, 57, 68, and 71 above, and further in view of Zhang et al. (J Immunol. 2012 Sep 1;189(5):2290-9. doi: 10.4049/jimmunol.1103495. Epub 2012 Jul 30).
The teachings of Abbot et al. in view of Jensen have been discussed supra. The combined references do not teach a CAR comprising a CD28 transmembrane domain (i.e., the limitations of instant claims 58 and 59).
Zhang et al., in the same field of endeavor, teaches construction of chimeric antigen receptors with differing TM domains (pg. 3, ¶2, Fig. 1):
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Zhang et al. further teaches (Results, pg. 6, ¶1): “[s]imilar to the CD8α TM domain, human CD28 TM domain resulted in higher surface expression of chNKp30 with or without the CD28 cytoplasmic (CYP) domain.”
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to have modified the combined references of Abbot et al. and Jensen further in view of Zhang et al. to replace the CLTA4 or PD-1 TM domain taught by Abbot et al. with the CD28 TM domain of Zhang et al. with a reasonable expectation of success, as Zhang et al. teaches methods of constructing CARs with the CD28 hinge domain that can be applied to the combined references of Abbot et al. and Jensen. One would have been motivated to make this change to increase surface expression of the CAR with the CD28 hinge domain, as taught by Zhang et al.
The instant claims are a prima facie obvious variant of the combined references of Abbot et al. in view of Jensen, and further in view of Zhang et al., especially in absence to the contrary.
Claims 68 and 70 is rejected under 35 U.S.C. 103 as being unpatentable over Abbot et al. (supra) in view of Jensen (supra), as applied to claims 51-54, 56, 57, 68, and 71 above, and further in view of Delaney et al. (supra).
The teachings of Abbot et al. in view of Jensen have been discussed supra. The combined references do not teach pharmaceutical compositions comprising the CAR and an acceptable carrier, or kits comprising the CAR (instant claims 68 and 70).
The instant claims are a prima facie obvious variant of the combined references of Abbot et al. in view of Jensen, and further in view of Delaney et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in absence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 51-54, 56-59, and 68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,454,562 (Pat ‘562, in Office Action mailed 10/09/2025) in view of Milone et al. (Mol Ther. 2009 Aug;17(8):1453-64. doi: 10.1038/mt.2009.83. Epub 2009 Apr 21, in Office Action mailed 10/09/2025, supra) and Alabanza et al. (Mol Ther. 2017 Nov 1;25(11):2452-2465. doi: 10.1016/j.ymthe.2017.07.013. Epub 2017 Jul 27, in Office Action mailed 10/09/2025, supra).
The invention of instant claims 51-54, 56-59, and 68 are a prima facie obvious variant of the invention claimed by Pat ‘562 in view of Milone et al. and Alabanza et al. for the same reasons set forth in the Office Action mailed 10/09/2025. Note that claim 56 is included for the same reasons discussed in the 35 U.S.C. § 103 rejection supra.
Claim 70 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,454,562 (Pat ‘562, supra) in view of Milone et al. (supra) and Alabanza et al. (supra), as applied to claims 51-54, 56-59, and 68 above, and further in view of Delaney et al. (WO2015066551, in Office Action mailed on 10/09/2025, supra).
The invention of instant claim 70 is a prima facie obvious variant of the invention claimed by Pat ‘562 in view of Milone et al. and Alabanza et al., and further in view of Delaney et al. for the same reasons set forth in the Office Action mailed 10/09/2025.
Claim 71 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,454,562 (Pat ‘562, supra) in view of Milone et al. (supra) and Alabanza et al. (supra), as applied to claims 51-54, 56-59, and 68 above, and further in view of Jensen (U.S. Patent 9,447,194, in Office Action mailed on 10/29/2025).
The invention of instant claim 71 is a prima facie obvious variant of the invention claimed by Pat ‘562 in view of Milone et al. and Alabanza et al., and further in view of Jensen for the same reasons set forth in the Office Action mailed 10/09/2025.
Claims 51-54, 56, 57, and 68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,738,116 (Pat ‘116) in view of Abbot et al. (U.S. PGPub 20150307623, supra).
Pat ‘116 claims chimeric antigen receptors (CARs) comprising an anti-CD19 antigen binding domain, a hinge domain, a TM domain, and an intracellular signaling domain (claim 1). Pat ‘116 further claims a CD3ζ ICD (claim 11).
Pat ‘116 does not claim the anti-CD19 CAR further comprising a CD28 hinge domain and a 4-1BB costimulatory domain.
Abbot et al. teaches polypeptides (claim 1), including chimeric antigen receptors (claim 42), comprising, from N to C terminus (¶[0032]): “…(i) an antigen-binding domain (e.g., an antigen binding domain that binds an antigen on a tumor cell, e.g., an antigen on a tumor cell described above); (ii) a CD28 hinge polypeptide sequence; (iii) a CTLA4 or PD-1 transmembrane domain; (iv) a 4-1BB costimulatory domain; and (v) a CD3ζ intracellular signaling domain.”
Abbot et al. further teaches that the antigen binding domain binds to a tumor-specific antigen (claim 20), including CD19 (claim 34). Abbot et al. further teaches the extracellular domains comprising scFvs (claim 19). Abbot et al. further teaches T-cell comprising CARs comprising these components can successfully treat tumors that the extracellular domain binds to, including B-cell lymphoma and prostate cancer (Examples 1-7).
It would have been obvious to one with ordinary skill in the art, to have modified the CAR claimed by Pat ‘116 in view of Abbot et al. to synthesize an anti-CD19 CAR further comprising a CD28 hinge domain, a TM domain, a 4-1BB costimulatory domain, and CD3ζ ICD (i.e. the limitations of instant claims 51-54 and 57-59) with a reasonable expectation of success, as Abbot et al. teaches such CAR components can be incorporated into a variety of CARs that one with ordinary skill in the art would be able to apply to the CAR claimed by Pat ‘116. One would have been motivated to make this change for the purposes of generating a function anti-CD19 CAR that can successfully target and eliminate CD19 expressing tumor cells. as Jensen teaches CARs with an anti-CD19 scFv comprising instant SEQ ID NO: 3.
Regarding instant claim 56, one with ordinary skill in the art would expect an anti-C19 CAR is expected to bind to CD19 whether it is expressed at low density or not. For example, Milone et al. teaches anti-CD19 binding CARs (Fig. 1).
Regarding claim 68, Abbot et al. teaches pharmaceutical compositions comprising the CAR and an acceptable carrier (¶[0153]), meeting the claim limitations.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 58 and 59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,738,116 (Pat ‘116, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Zhang et al. (J Immunol. 2012 Sep 1;189(5):2290-9. doi: 10.4049/jimmunol.1103495. Epub 2012 Jul 30, supra).
The teachings of Abbot et al. in view of Jensen have been discussed supra. The combined references do not teach a CAR comprising a CD28 transmembrane domain (i.e., the limitations of instant claims 58 and 59).
The invention of instant claims 58 and 59 is a prima facie obvious variant of the invention claimed by Pat ‘116 in view of Abbot et al., and further in view of Zhang et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra.
Claim 70 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,738,116 (Pat ‘116, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Delaney et al. (supra).
The invention of instant claim 70 is a prima facie obvious variant of the invention claimed by Pat ‘116 in view of Abbot et al., and further in view of Delaney et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra.
Claim 71 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,738,116 (Pat ‘116, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Jensen (supra).
The invention of instant claim 70 is a prima facie obvious variant of the invention claimed by Pat ‘116 in view of Abbot et al., and further in view of Delaney et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra.
Claims 51-54, 56, 57, and 68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,980,640 (Pat ‘640) in view of Abbot et al. (supra).
Pat ‘640 claims chimeric antigen receptors (CARs) comprising an anti-CD19 antigen binding domain, a hinge domain, a TM domain, and an intracellular signaling domain (claim 1). Pat ‘116 further claims a CD3ζ ICD (claim 7).
Pat ‘640 does not claim the anti-CD19 CAR further comprising a CD28 hinge domain and a 4-1BB costimulatory domain.
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘640 in view of Abbot et al. for the same reasons discussed for Pat ‘116 supra.
Claim 58 and 59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,980,640 (Pat ‘640, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Zhang et al. (supra).
The invention of instant claims 58 and 59 is a prima facie obvious variant of the invention claimed by Pat ‘640 in view of Abbot et al., and further in view of Zhang et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra.
Claim 70 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,980,640 (Pat ‘640, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Delaney et al. (supra).
The invention of instant claim 70 is a prima facie obvious variant of the invention claimed by Pat ‘640 in view of Abbot et al., and further in view of Delaney et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra.
Claim 71 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,980,640 (Pat ‘640, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Jensen (supra).
The invention of instant claim 70 is a prima facie obvious variant of the invention claimed by Pat ‘640 in view of Abbot et al., and further in view of Delaney et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra.
Claims 51-54, 56, 57, and 68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,473,344 (Pat ‘344) in view of Abbot et al. (supra).
Pat ‘344 claims chimeric antigen receptors (CARs) comprising an anti-CD19 scFv antigen binding domain (claims 1, 4, and 6), and an intracellular signaling domain comprising 4-1BB and CD3ζ (claim 10).
Pat ‘344 does not claim the anti-CD19 CAR further comprising a CD28 hinge domain and a 4-1BB costimulatory domain.
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘344 in view of Abbot et al. for the same reasons discussed for Pat ‘116 supra.
Claims 58 and 59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,473,344 (Pat ‘344, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Delaney et al. (supra).
The invention of instant claims 58 and 59 are a prima facie obvious variant of the invention claimed by Pat ‘344 in view of Abbot et al., and further in view of Delaney et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra.
Claim 70 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,473,344 (Pat ‘344, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Delaney et al. (supra).
The invention of instant claim 70 is a prima facie obvious variant of the invention claimed by Pat ‘344 in view of Abbot et al., and further in view of Delaney et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra.
Claim 71 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,473,344 (Pat ‘344, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Jensen (supra).
The invention of instant claim 70 is a prima facie obvious variant of the invention claimed by Pat ‘344 in view of Abbot et al., and further in view of Delaney et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra.
Claims 51-54, 56, 57, and 68 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34, 36, 46, 47, 49-81, 97, and 98 of copending Application 17/149,541 (herein App ‘541) in view of Abbot et al. (supra).
App ‘541 claims chimeric antigen receptors (CARs) comprising an anti-CD19 scFv antigen binding domain (claims 1 and 3), as well as the CAR further comprising transmembrane domain and a hinge domain (claims 9 and 15).
App ‘541 does not claim the anti-CD19 CAR further comprising a CD28 hinge domain and a 4-1BB costimulatory domain.
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘541 in view of Abbot et al. for the same reasons discussed for Pat ‘116 supra. This is a provisional double patenting rejection.
Claims 58 and 59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34, 36, 46, 47, 49-81, 97, and 98 of copending Application 17/149,541 (App ‘541, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Zhang et al. (supra).
The invention of instant claim 70 is a prima facie obvious variant of the invention claimed by App ‘541 in view of Abbot et al., and further in view of Zhang et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra. This is a provisional double patenting rejection.
Claim 70 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34, 36, 46, 47, 49-81, 97, and 98 of copending Application 17/149,541 (App ‘541, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Delaney et al. (supra).
The invention of instant claim 70 is a prima facie obvious variant of the invention claimed by App ‘541 in view of Abbot et al., and further in view of Delaney et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra. This is a provisional double patenting rejection.
Claim 71 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34, 36, 46, 47, 49-81, 97, and 98 of copending Application 17/149,541 (App ‘541, supra) in view of Abbot et al. (supra), as applied to claims 51-54, 56, 57, and 68 above, and further in view of Jensen (supra).
The invention of instant claim 70 is a prima facie obvious variant of the invention claimed by App ‘541 in view of Abbot et al., and further in view of Delaney et al. for the same reasons set forth in the 35 U.S.C. § 103 rejection supra. This is a provisional double patenting rejection.
Conclusion
No claim is allowed.
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Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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