DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
2. Claims 1-32 were previously cancelled. Claims 34-39 were cancelled. Claims 33 and 40-44 are under consideration in this office action.
Maintained Grounds of Rejection
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.
3. Claims 33 and 42-44 are rejected under 35 U.S.C. 103 as being unpatentable over Campana et al., (US PG PUB 20150139943 published May 15, 2015; priority to Oct. 17, 2013) in view of Olson et al., (WO2014093406 published June 2014; priority to Dec 2013).
The claims are drawn to a method for treating a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor, wherein the chimeric antigen receptor comprises: a chlorotoxin comprising SEQ ID NO:1; a spacer domain comprising any of SEQ ID NOs:2-12; a transmembrane domain selected from: a CD4 transmembrane domain comprising SEQ ID NO:16, a CD8 transmembrane domain comprising SEQ ID NOs: 17, 18 or 19, and a CD28 transmembrane domain comprising SEQ ID NO:14 or 15; a co-stimulatory domain selected from a CD28 co-stimulatory domain comprising SEQ ID NO: 22 or 23 and a 41-BB co-stimulatory domain comprising SEQ ID NO:24; and a CD3z (zeta) signaling domain comprising SEQ ID NO: 21.
Campana et al., teach chimeric receptors comprising an extracellular domain with affinity and specific for the Fc portion of an immunoglobulin molecule (Ig) (e.g., an extracellular ligand-binding domain of F158 FCGR3A or V158 FCGR3A variant); a transmembrane domain (e.g., a transmembrane domain of CD8α); at least one co-stimulatory signaling domain (e.g., a co-stimulatory signaling domain of 4-1BB); and a cytoplasmic signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM) (e.g., a cytoplasmic signaling domain of CD3ζ) [abstract]. Such immune cells can be used to enhance antibody-dependent cell-mediated cytotoxicity and/or to enhance antibody-based immunotherapy, such as cancer immunotherapy [abstract]. The methods are for enhancing antibody-dependent cell-mediated cytotoxicity (ADCC) in a subject. The method comprises administering to a subject in need of the treatment (e.g., a human cancer patient) an effective amount of host cells that express any of the chimeric receptors provided herein. The host cells are immune cells such as T cells [para 21].
Campana et al., teach a spacer domain comprising instant SEQ ID NOs:8, whereby Campana teach CD8-alpha protein hinge region/transmembrane domain consisting of amino acid sequence SEQ ID NO:58. Campana et al., teach a transmembrane domain selected from: a CD4 transmembrane domain comprising SEQ ID NO:16 whereby Campana et al., teach a CD4 Transmembrane domain as SEQ ID NO:14. Campana et al., teach a CD8 transmembrane domain comprising instantly claimed SEQ ID NO:19 within Campana et al’s CD8-alpha protein hinge region/transmembrane domain consisting of amino acid sequence SEQ ID NO:58.
Campana et al., teach a co-stimulatory domain selected from a CD28 co-stimulatory domain comprising instantly claimed SEQ ID NO: 23 at Campana et al’s SEQ ID NO;12 within Example 2. Campana et al., teach instantly claimed 41-BB co-stimulatory domain comprising SEQ ID NO:24; by disclosing 4-1BB (CD137) protein co-stimulatory/signaling domain, SEQ ID 59 [see also claim 8].Campana et al., teach the instantly claimed CD3z (zeta) signaling domain comprising SEQ ID NO: 21 by describing cytoplasmic signaling domain of CD3ζ consists of the amino acid sequence of SEQ ID NO: 60 [See claim 9]. Therefore, Campana et al., teach instant claim 33. Campana et al., teach instantly recited SEQ ID NOs: 8, 16, 19, 21, 23 and 24 with 100% sequence identity. Please see the office action mailed May 16, 2025 for the full sequence alignments.
The subject may be a human patient suffering from a cancer and the therapeutic antibody is for treating the cancer. In some examples, the cancer is a head and neck cancer, glioma or glioblastoma [para 25]. It is noted that glioblastomas are the most aggressive and most common type of malignant glioma. The terms “treat”, “treatment”, and the like mean to relieve or alleviate at least one symptom associated with such condition, or to slow or reverse the progression of such condition. Within the meaning of the present disclosure, the term “treat” also denotes to arrest, delay the onset (i.e., the period prior to clinical manifestation of a disease) and/or reduce the risk of developing or worsening a disease. For example, in connection with cancer the term “treat” may mean eliminate or reduce a patient's tumor burden, or prevent, delay or inhibit metastasis, etc [para 55]. Thus teaching claims 42-44. Campana et al., teach instantly recited SEQ ID NOs: 8, 16, 19, 21, 23 and 24 with 100% sequence identity.
Therefore, Campana et al., teach a method for treating a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor, wherein the chimeric antigen receptor comprises: a spacer domain comprising any of SEQ ID NO: 8, a transmembrane domain selected from: a CD4 transmembrane domain comprising SEQ ID NO:16, a CD8 transmembrane domain comprising SEQ ID NO:19; a co-stimulatory domain selected from a CD28 co-stimulatory domain comprising SEQ ID NO: 23 and a 41-BB co-stimulatory domain comprising SEQ ID NO:24; and CD3z (zeta) signaling domain comprising SEQ ID NO: 21; but does not teach the inclusion of chlorotoxin.
Olson et al., teach methods are provided for treating a disease associated with cells expressing a chlorotoxin target, the method comprising: administering, to a subject in need thereof, a therapeutically effective amount of a pharmaceutical composition comprising a peptide according to the present disclosure or a composition comprising a peptide of the present disclosure, thereby treating the disease [para 13].
The disease comprises cancerous tissue associated with glioma [para 63]. Olson et al., teach treating gliomas and malignant gliomas such as astrocytomas ependymomas and other brain tumors [para 126]. Thus teaching claims 33 and 42-44. The peptides having D-amino acids and being based on a chlorotoxin scaffold, e.g., D-amino acid chlorotoxin and/or D-amino acid chlorotoxin variants. The peptides based on chlorotoxin can include varying amounts of D-amino acids [para 84]. The methods include administering a D-amino acid chlorotoxin and/or D-amino acid chlorotoxin variant described herein to a subject with a tumor such that the peptide selectively targets tumor tissue over normal tissue [para 127]. Olson et al., the targeting capability (e.g., tumor). Some selected properties include stability/oral bioavailability, 2) controllable/programmable pharmacokinetics, 3) ability to disrupt protein/protein interactions, 4) ability to cross the blood- brain barrier, 5) ability to penetrate cells, ability to penetrate specific organelles and/or cellular compartments, 6) potential for selectable tissue/organ targeting, 7) ability to be conjugated specifically to drugs, 8) "programmable diversity" 9) readily engineered and 10) potential for programmable intracellular targeting [para 53]. Olson et al., teach an IgK signal peptide (signaling domain) with linkers (spacers) and chlorotoxin fusion protein. Olson et al., instantly claimed SEQ ID NO:1 with 100% sequence identity. Please see the office action mailed May 16, 2025 for the full sequence alignments.
Therefore, it would have been prima facie obvious to combine Campana et al’s treatment of a glioblastoma, a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor, wherein the chimeric antigen receptor comprises: a spacer domain, a transmembrane domain selected from: a CD4 transmembrane domain, a CD8 transmembrane domain, a CD28 transmembrane domain, and a CD3 z transmembrane domain; a costimulatory domain; and CD3 z (zeta) signaling domain; and incorporate the chlorotoxin as taught by Olson et al., in order to treat malignant gliomas such as glioblastomas, astrocytomas and ependymomas. No more than routine skill would have required to modify Campana et al., teach a method for treating a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor, wherein the chimeric antigen receptor comprises: a spacer domain comprising any of SEQ ID NO: 8, a transmembrane domain selected from: a CD4 transmembrane domain comprising SEQ ID NO:16, a CD8 transmembrane domain comprising SEQ ID NO:19; a co-stimulatory domain selected from a CD28 co-stimulatory domain comprising SEQ ID NO: 23 and a 41-BB co-stimulatory domain comprising SEQ ID NO:24; and CD3z (zeta) signaling domain comprising SEQ ID NO: 21; to include the chlorotoxin as taught by Olson et al., in order to Olson et al., selectively target malignant gliomas such as astrocytomas ependymomas and other brain tumors. Taken all together, it would have been obvious to one of ordinary skill in this art before the filing of the instant application that the CAR of Campana et al., which treat glioma and malignant glioma cells, while incorporating Olson’s chlorotoxin which also specifically treat malignant gliomas; thus teaching the same purpose as Campana et al. Such would provide the advantage of additivity or synergism between the CAR of Campana and Olson’s chlorotoxin. This is an inclusion CAR and chlorotoxin against glioblastoma to yield a predictably functional therapy with a very high expectation of success owed to the successes of Campana et al., and Olson et al., as discussed above.
Response to Arguments
4. Applicant’s arguments, filed May 7, 2026, with respect to the rejection of
claims 33 and 42-44 under Campana et al., in view of Olson et al., is maintained.
Applicants allege that they are confused that Campana et al., teach the treatment of a glioblastoma and/or a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor, wherein the chimeric antigen receptor comprises: a spacer domain, a transmembrane domain selected from: a CD4 transmembrane domain, a CD8 transmembrane domain, a CD28 transmembrane domain, and a CD3 z transmembrane domain; a costimulatory domain; and CD3 z (zeta) signaling domain; but does not teach the inclusion of a chlorotoxin. In this case, no more than routine skill would have been required to incorporate Olson et al/. chlorotoxin into Campana treatment method and chimeric antigen receptor in order to specifically target tumor tissue. One of ordinary skill in the would have a reasonable expectation of success by incorporating the chlorotoxin as taught by Olson et al., in order to treat malignant gliomas such as glioblastomas, astrocytomas and ependymomas.
Applicants argue that neither Campana et al., nor Olson et al., teach the utilization of chlorotoxin as a direct targeting domain to bind glioma cells and kill them. However, Applicants attention is directed to the instant claims reciting “…method for treating a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor…” . In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies i.e., targeting action and killing action are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Therefore, Applicants repeated arguments about targeting and killing are not persuasive, because neither targeting nor killing are a requirement recited by any rejected claims.
In response to applicant's argument that the prior art does not teach targeting and killing of glioma cells, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art chimeric antigen receptor comprising a chlorotoxin having SEQ ID NO:1; a spacer domain having SEQ ID NO: 8; a transmembrane domain selected from: a CD4 transmembrane domain comprising SEQ ID NO:16, a CD8 transmembrane domain having SEQ ID NO:19, a co-stimulatory domain selected from a CD28 co-stimulatory domain having SEQ ID NO: 23 and a 41-BB co-stimulatory domain having SEQ ID NO:24; and a CD3z (zeta) signaling domain comprising SEQ ID NO: 21, thereby providing structures capable of performing the intended use, then the prior art components and methods meet the claimed limitations.
Applicants argue that the modification of the CAR of Campana et al., bears no resemblance to the CAR of the present claims because it exemplifies a universal chimeric receptor and does not target cancer cells. In response, Campana et al., teach targeting by the antibody or such other anti-tumor molecule comprising the Fc portion. Therefore Campana et al’s teaching is not limited to the full length antibody. Moreover, the instantly rejected claims do not exclude an antibody. Campana et al., in view of Olson et al., teach a method for treating a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor, wherein the chimeric antigen receptor comprises: a spacer domain comprising any of SEQ ID NO: 8, a transmembrane domain selected from: a CD4 transmembrane domain comprising SEQ ID NO:16, a CD8 transmembrane domain comprising SEQ ID NO:19; a co-stimulatory domain selected from a CD28 co-stimulatory domain comprising SEQ ID NO: 23 and a 41-BB co-stimulatory domain comprising SEQ ID NO:24; and CD3z (zeta) signaling domain comprising SEQ ID NO: 21 as taught by Campana et al; while the inclusion of chlorotoxin is taught by Olson et al.
Applicants argue that there is no data that Olson et al., can bind or kill a glioma cell. Applicants are reminded that reduction to practice is not the only way a patent publication can teach an inventive concept. Therefore, the lack of data does not preclude Olson et al., from teaching the chlorotoxin can target a glioma. The MPEP section 2123 teaches that patents are relevant as prior art for all they contain, “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir.1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. “The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.”). Therefore applicant’s argument is not persuasive especially when Olson et al., the targeting capability (e.g., tumor). Some selected properties include stability/oral bioavailability, potential for selectable tissue/organ targeting, and ability to be conjugated specifically to drugs, and/or readily engineered for programmable targeting. Olson et al., teach a signaling domain with linkers (spacers) and chlorotoxin fusion protein. Olson et al., instantly claimed SEQ ID NO:1 with 100% sequence identity. Therefore, Olson et al., teach the that one of ordinary skill would incorporate the chlorotoxin because it can be conjugated to other drugs and ability to be targeted.
Applicants argue that no combination of Campana and Olson provide a reasonable expectation of success in practicing the claimed method because Campana does not teach or suggest that their CAR T cells target and kill cancer cells without the aid of an antibody- based immunotherapy. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See 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), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Campana et al., designed chimeric receptors comprising an extracellular domain with affinity and specificity for the Fc portion of an IgG antibody, a transmembrane domain, at least one co-stimulatory signaling domain, and a cytoplasmic signaling domain that comprises an immunoreceptor tyrosine-based activation motif (ITAM). Immune cells expressing such a chimeric receptor construct would enhance efficacy of immune therapy enhancing Antibody dependent cell-mediated cytotoxicity (ADCC) activity.
Applicants urge that nothing in Campana shows that administering a CAR T cell immune therapy can directly target and kill cancer cells. Therefore, Applicants are reminded that the instant claims do not require direct killing of cancer cells. The instant claims recite a method for treating a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor. At best the claims are required to treat a malignant glioma. Campana et al., teach administration and treatment of a glioblastoma; while Olson et al., teach administration and treatment of astrocytomas and ependymomas. Campana et al., and Olson et al., similarly define treatment to include eliminate or reduce a patient's tumor burden, or prevent, delay or inhibit metastasis and/or treatment improves or a treatment may delay worsening of a progressive disease in an individual, or prevent onset of additional associated diseases. Therefore, the instantly rejected claims recite treatment and the prior art references teach treatment. Therefore this argument is not persuasive.
Contrary to Applicants arguments, Campana et al., teach a method for treating a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor, wherein the chimeric antigen receptor comprises: a spacer domain comprising any of SEQ ID NO: 8, a transmembrane domain selected from: a CD4 transmembrane domain comprising SEQ ID NO:16, a CD8 transmembrane domain comprising SEQ ID NO:19; a co-stimulatory domain selected from a CD28 co-stimulatory domain comprising SEQ ID NO: 23 and a 41-BB co-stimulatory domain comprising SEQ ID NO:24; and CD3z (zeta) signaling domain comprising SEQ ID NO: 21. The claims do not exclude any components taught by Campana et al. Therefore, taken all together, it would have been obvious to one of ordinary skill in this art before the filing of the instant application that the CAR of Campana et al., which treat glioma and malignant glioma cells, and incorporate Olson’s chlorotoxin because it also specifically targets and treat malignant gliomas. Therefore the teaching of Campana and Olson both teach the same purpose.
Applicants argue the claims do not need to recite direct targeting of glioma cells; yet Applicants repeatedly argue that the prior art references do not recite direct targeting of glioma cells. The Office agrees that the recitation is not necessary. The Office has merely pointed out that direct targeting of glioma cells is not recited by the claims, yet Campana et al., teach a method for treating a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor, while Olson teach a method for treating a malignant glioma, a disease associated with cells expressing a chlorotoxin target, comprising administering a therapeutically effective dose of chlorotoxin which has glioma targeting capability and the ability to be conjugated specifically to other drugs.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See 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), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, exemplary data is not needed to show Campana et al., clearly teach a method for treating a glioblastoma, a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor, comprising a spacer domain; a transmembrane domain selected from: a CD4 transmembrane domain, a CD8 transmembrane domain, and a CD28 transmembrane domain; a co-stimulatory domain selected from a CD28 co-stimulatory domain; a 41-BB co-stimulatory domain; and a CD3z (zeta) signaling domain with the exact same sequences. Again, data is not required to show Olson taught the instantly claimed chlorotoxin with the exact same sequence will treat malignant gliomas. Both Campana et al., and Olson et al., provided prior art specifications, identified by paragraph each and every claimed limitation. Furthermore, the Olson et al., reference clearly teach the advantages and benefits of including the chlorotoxin within the CAR as taught by Campana et al.
Again, Campana et al., teach treatment of a glioblastoma, a malignant glioma comprising administering a therapeutically effective dose of T cells expressing a chimeric antigen receptor, wherein the chimeric antigen receptor comprises: a spacer domain, a transmembrane domain selected from: a CD4 transmembrane domain, a CD8 transmembrane domain, a CD28 transmembrane domain, and a CD3 z transmembrane domain; a costimulatory domain; and CD3 z (zeta) signaling domain. Olson et al., teach methods are provided for treating astrocytomas and/or ependymomas with cells expressing a chlorotoxin target. Olson et al., teach a method comprising administering an effective dose of a composition including fusion proteins, peptides, or conjugates thereof to a subject with cancerous tissue (e.g., a tumor) such that the peptide selectively targets cancerous tissue (e.g., tumor tissue) over normal tissue [par 108]. Therefore, incorporating the chlorotoxin as taught by Olson et al., into the CAR of Campana would have been advantageous as taught by Olson in order to improve bioavailability and target malignant cancers like malignant gliomas. Thus, the argument is not persuasive.
Applicants point to their Examples 6A-7C, 10-11 and 12 showing that a CLTX CAR can reduce tumor growth in a murine xenograft model of a glioblastoma. It is noted, that the Office does not dispute the fact that a CLTX CAR will treat a glioblastoma upon administration. Campana et al., clearly and specifically teach treatment of malignant glioma, and astrocytoma and/or glioblastomas with chimeric antigen receptor comprising: a spacer domain, a transmembrane domain selected from: a CD4 transmembrane domain, a CD8 transmembrane domain, a CD28 transmembrane domain, and a CD3 z transmembrane domain; a costimulatory domain; and CD3 z (zeta) signaling domain. Olson et al., teach treating malignant gliomas, astrocytomas ependymomas and other brain tumors administering linkers (spacers) and chlorotoxin fusion protein. Therefore, the administration to gliomas would have been obvious.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. In this case, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine). Taken all together, it would have been obvious to one of ordinary skill in this art before the filing of the instant application that the CAR of Campana et al., which treat glioma and malignant glioma cells, and incorporate Olson’s chlorotoxin which was known to be conjugation ready and well-known to treat malignant gliomas. Such would provide the advantage of additivity or synergism between the CAR of Campana and Olson’s chlorotoxin to treat malignant gliomas. The an inclusion CAR and chlorotoxin against glioblastoma to yield a predictably functional therapy with a very high expectation of success owed to the successes of Campana et al., and Olson et al., as discussed above. Therefore the rejection is maintained despite applicants arguments.
Claim Objections
5. Claims 40-41 are objected to because of the following informalities: Claims 40-41 depend upon rejected claim 33. Appropriate correction is required.
Response to Arguments
6. Applicant's arguments filed May 7, 2026 have been fully considered but they are not persuasive. The objection is maintained despite Applicants acknowledgement of the objection. In this case, claims 40-41 are still objected to because the claims are dependent upon rejected claim 33. Therefore, the objection is maintained.
Pertinent Art
7. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
Caligiuri et al., (WO 2016164370 published Oct. 13, 2016; priority to April 6, 2015).
Forman et al., (WO2015105522 published July 16, 2015; priority to March 14, 2014) teach 100% sequence identity to at least instantly claimed SEQ ID NO:2 (IgG4 Fc region CH2 domain mutant, SEQ ID:20); 3 (IgG4 Fc region CH2 domain mutant, SEQ ID:20); 4 (IgG4 Fc region mutant (N79Q), SEQ ID:17); 5(IgG4 Fc region CH2 domain mutant, SEQ ID:20); 10, 11 (IgG4 Fc region mutant (S10P/L17E/N79Q), SEQ ID:19) and 12 (IgG4 Fc region CH2 domain mutant, SEQ ID:20).
Alvarez et al., (US Pat Pub 20110311445 published May 2011; priority to June 2003). Cooper et al., (WO2015123642) teach chimeric antigen receptors (CAR) to treat gliomas. Hallahan et al., (WO2015031645) teach antibody specifically binds 14-3-3 epsilon and comprises a heavy chain CDR3 to treat brainstem gliomas, brain tumors (cerebellar astrocytoma, cerebral astrocytoma/malignant glioma, ependymoma, medulloblastoma, supratentorial primitive neuroectodermal tumors, visual pathway and hypothalamic gliomas).
Conclusion
8. No claims allowed. However SEQ ID NOs:26-40 are free of the prior art.
9. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Peter Paras, can be reached on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/JANA A HINES/Primary Examiner, Art Unit 1645
Prosecution Insights