DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2 Applicant's amendment, filed on 04/18/2024, is acknowledged.
3. Claims 1-7 and 10-21 are pending.
4. Applicant’s IDS, filed 07/13/2023, is acknowledged.
5. The following is a quotation of 35 U.S.C. 112(b) (Pre AIA , 35 U.S.C. 112, second paragraph):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
6. Claims 2, 12-15 and 17 are rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
(a) The “structure” recited in claim 2, lacks sufficient antecedent basis is base claim 1.
(b) The recitation “derived from” in claims 12-15 is indefinite because it is unclear what changes or how many changes could have occurred to result in a derivative. Derivation only describes the source and not the result. It is suggested that claim 12 for example recites “L is a macrophage colony stimulating factor signal peptide” to overcome the rejection.
(c ) The “amino acid sequence” in claim 17, lacks sufficient antecedent bases in base claim 1. It is suggested that the claim recites, “wherein the CAR is shown in SEQ ID NO: 3”.
7. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(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.
8. Claims 1-7 and 10-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recited a genus of CARs comprising a genus of VH and VL comprising 6 CDRs without antigen specificity and without framework.
Claims 5 recites a genus of immune cell comprising the CARs.
However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of treating a disease including cancer or tumor, B7-H3-ositive tumor such as AML. The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus.
With respect to the recitation an antibody which comprise all 6 CDRs of the antibody without antigen specificity and lacks the framework, the Examiner directs Applicant's attention to the training material given by Bennett Celsa, Example 2: (Ab genus: modified CDR's) slides 34-40. Example 2 of the Training material which requires that the claims explicitly recite the binding antigen in addition to all 6 CDR regions for fulfillment of the written description requirements under § 112, 1. Slide 39 indicates that a claim encompasses antibodies with 6 intact CDRs as well as a subgenus of antibodies that encompass up to 10% variation (fragments and/or analogs) in the 6 CDRs lacks written description. Slide 40 provide the conclusion that, a single antibody species would not be deemed by one of skill in the art to be representative of a claim that defines an antibody that binds antigen X comprising at least 90% homology to the 6 CDR of the VH and VL chains. Instants lacks both the antigen specificity, i.e., B7-H7 as well as the framework.
Claims 5 recites a genus of immune cell comprising the CARs. However, Red blood cells which lacks nucleic acid and machinery to express engineered receptors is impractical cells for chimeric antigen receptor (CAR) technology. Further, B cells and neutrophils are not utilized as primary CAR chassis platforms due to sort lifespans, genetic intractability, and lack of targeted tumor-killing.
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.
9. Claims 18-21 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating B7-H3-postive tumor including acute myeloid leukemia (AML) with a T-cell expressing CAR comprising anti-B7-H3 antibody comprising the CDRs of SEQ ID NOs: 6-11, does not reasonably provide enablement for each and every disease with an immune cell expressing a CAR comprising anti-B7-H3 antibody comprising the CDRs of SEQ ID NOs: 6-11. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The instant claims are drawn to a large genus of methods which have not been developed yet to the point where a specific benefit exists in currently available form.
In Wands , the court noted that the there was no disagreement as to the facts, but merely a disagreement as to the interpretation of the data and the conclusion to be made from the facts. In re Wands, 858 F.2d at 736-40, 8 USPQ2d at 1403-07. The court held that the specification was enabling with respect to the claims at issue and found that "there was considerable direction and guidance" in the specification; there was "a high level of skill in the art at the time the application was filed;" and "all of the methods needed to practice the invention were well known." Id. at 740, 8 USPQ2d at 1406. After considering all the factors related to the enablement issue, the court concluded that "it would not require undue experimentation to obtain antibodies needed to practice the claimed invention." Id. , 8 USPQ2d at 1407.
The specification at page 31disclsoes that the present invention not only demonstrates that the B7-H3-CAR T cell can effectively and specifically eliminate AML tumor cells expressing B7-H3 antigen in vitro and in vivo, but also demonstrates its good safety, laying a foundation for the clinical use of B7-H3-CAR T cells for the treatment of AML. Compared with the most commonly used CD33-CAR T and CD123-CAR T cells which require prior bone marrow clearance before administration, B7-H3-CAR T cell not only has the possibility of prolonging the survival of relapsed refractory AML patients, but also simplifies the difficulty of administration of CAR T treatment in clinical practice and reduces risk in the patient.
The specification fails to provide empirical data showing that B7-H3-CAR T cells would treat each and every disease. The specification lacks animal models for the whole genus of the target diseases.
Given the relatively incomplete understanding in correlating in vitro assays and in vivo animal models to clinical treatment of cancer involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims, the claims are not enabled. See MPEP 2164.08
If the use disclosed is of such nature that the art is unaware of successful treatments with chemically analogous compounds, a more complete statement of how to use must be supplied.
The determination that "undue experimentation" would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988).
If the use disclosed is of such nature that the art is unaware of successful treatments with chemically analogous compounds, a more complete statement of how to use must be supplied.
"The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements...However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims.” MPEP § 2164.03.
"Substantiating evidence may be in the form of animal tests which constitute recognized screening procedures with clear relevance to utility in humans. See Ex parte Krepelka, 231 USPQ 746 (Board of Patent Appeals and Interferences 1986) and cases cited therein." Ex parte Maas, 9 USPQ2d 1746.
Further, in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297-1303 (CAFC 2005), the court states “If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the 'inventor' would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis.”
The MPEP states that the issue of "correlation" is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. See MPEP 2164.02.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
10. 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.
11. Claims 1-7 and 10-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-9 and 11-14 of copending Application No. 18261398 (US 20250002583 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the `398 applicant teaches a CAR construct, wherein the CAR construct comprises an scFv region specifically binding to CD276, and the scFv comprises a heavy chain variable region of an antibody, which comprises following three complementarity determining regions (CDRs):
a CDR1 set forth in SEQ ID NO: 1,
a CDR2 set forth in SEQ ID NO: 2, and
a CDR3 set forth in SEQ ID NO: 3 or 7 and
a light chain variable region of an antibody, which comprises following three complementarity
determining regions (CDRs):
a CDR1' set forth in SEQ ID NO: 4,
a CDR2' set forth in SEQ ID NO: 5, and
a CDR3' set forth in SEQ ID NO: 6,
A recombinant immune cell expressing an exogenous CAR construct.
A method for preventing or treating a CD276-positive tumor CD276-related disease, wherein the method comprises administering an antibody targeting CD276, an antibody-drug conjugate of the antibody, or a CAR-T cell expressing the antibody- or a combination thereof to a subject in need thereof, wherein the antibody targeting CD276 comprises:
(1) a heavy chain variable region of an antibody, which comprises following three
complementarity determining regions (CDRs):
a CDR1 set forth in SEQ ID NO: 1,
a CDR2 set forth in SEQ ID NO: 2, and
a CDR3 set forth in SEQ ID NO: 3 or 7 and
a light chain variable region of an antibody, which comprises following three complementarity
determining regions (CDRs):
a CDR1' set forth in SEQ ID NO: 4,
a CDR2' set forth in SEQ ID NO: 5, and
a CDR3' set forth in SEQ ID NO: 6,
The claims of the `398 applications anticipate the instant claims
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
12. No claim is allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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August 10, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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