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 .
Claim Status
To expedite the compact prosecution, the Examiner is pursuing the claims dated 17 October 2024, in which applicant canceled claims 1-49 and added new claims 50-68.
Therefore, claims 50-68 are pending in the application.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 50-61 and 68 drawn to a nucleic acid construct or constructs comprising a CAR and a transcription factor or a variant thereof in the reply filed on 24 June 2026 is acknowledged.
Claims 62-67 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 50-61 and 68 are under current examination.
Priority
This application was filed 08/06/2024 and is a Divisional of 16096562, filed 10/25/2018, now U.S. Patent # 12060394. The National Stage entry of PCT/US2017/030284, international filing date: 04/28/2017 and claims priority from Provisional Application 62328936, filed 04/28/2016. Thus, the earliest possible priority for the instant application is 04/28/2016.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/24/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner and the signed and initialed PTO Forms 1449 are mailed with this action.
New Claim Rejections - 35 USC § 112(a)
(Written Description)
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 55 and 56 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.
As per MPEP 2163(I), "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Also, as per MPEP 2163.03(V), there is a presumption that an adequate written description of the claimed invention is present in the specification as filed.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Possession may be shown in a variety of ways, for example, possession may be shown by describing an actual reduction to practice of the claimed invention. A specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. Cooper v. Goldfarb, 154 F.3d 1321, 1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) ("[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim."); Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) ("[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose."); Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves). Alternatively, applicant may present that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it").
Finally, MPEP 2163.04 describes the burden on the examiner with regard to the Written Description requirement, stating that in rejecting a claim, the examiner must set forth express findings of fact which support the lack of written description conclusion. These findings should:
(A) Identify the claim limitation(s) at issue; and
(B) Establish a prima facie case by providing reasons why a person skilled in the art at the time the application was filed would not have recognized that the inventor was in possession of the invention as claimed in view of the disclosure of the application as filed.
Dependent claims 55 encompass a genus of a nucleic acid sequence encoding an amino acid sequence having at least 80-99% or 100% identity with TZ.47 scFv.
Dependent claims 56 encompass a genus of nucleic acid sequence encoding an amino acid sequence having at least 80-99% or 100% identity with TZ.47-28-3z, Tz.47-28-3zMsTBET, Tz.47-28-3zMsTBET-STOP and/or Tz.47-28-3zMsTBET-
TBOX Deletion.
Teachings of the Specification:
In the specification Applicant discloses the B7H6-specific CAR construct (the ''TZ.47 CAR") wherein the B7-H6-specific monoclonal antibody clone 47.39 was used as the basis for the antigen receptor, fused in frame to the endodomains of CD28 and CD3 zeta. The anti-B7H6 scFv (amino acid SEQ ID NO: 13, nucleic acid sequence SEQ ID NO: 24) was generated by fusing the variable regions of the 47.39 antibody heavy chain (VH, aa 1-134) and light chain (VL, aa 23-129) in frame with a 15 amino acid glycine (G)-serine (S) linker (SPEC [413-414]). Therefore, disclosure does not support the full claim scope of identity with different variant of amino acid sequence, it has support for 100% identity to the SEQ ID NOs 13 or 24. Similarly, SEQ ID Nos: 25, 26, 34-39 (SPEC [429-436]).
Working examples of the specification:
In regards to claims 50 and 56 encompass a genus of an antibody fragment derived from human, humanized, or chimeric scFv antigen binding domain that specifically recognizes TZ.47 scFv and comprising the amino acid sequence of at least 80-99% identity, however, it only describes SEQ ID NO:13 or 24 for TZ.47 scFV [413], SEQ ID NOs: 25-26 for the Tz.47-28-3z [231, 413], SEQ ID NO: 34-35 for Tz.47-28-3zMsTBET [234], SEQ ID NO: 36-37 for Tz.47-28-3zMsTBET-STOP [235], [431] and SEQ ID NO: 38-39 for Tz.47-28-3zMsTBET-TBOX Deletion [236], [431]. The Examiner could only find the amino acid sequence of 100% identity with TZ.47 scFv, Tz.47-28-3z, Tz.47-28-3zMsTBET, Tz.47-28-3zMsTBET-STOP and Tz.47-28-3zMsTBET-TBOX Deletion but not amino acids sequence for 80%-99% identical. Therefore, the amino acid sequence of at least 80-99% identity with TZ.47 scFv, Tz.47-28-3z, Tz.47-28-3zMsTBET, Tz.47-28-3zMsTBET-STOP and Tz.47-28-3zMsTBET-TBOX Deletion is insufficiently detailed written description to show that Applicant had claimed a genus of antibody fragments recognizes amino acid sequence 80-99% identity.
State of the Art at the Time of Filing:
The claimed invention is not well established at the time of filling. Although, one of skill in the art would neither expect nor predict the appropriate functioning of the antibody fragment that the recognizes B7-H6 and comprising the amino acid sequence of at least 80-99% identity with Tz.47-28-3z, Tz.47-28-3zMsTBET, Tz.47-28-3zMsTBET-STOP and Tz.47-28-3zMsTBET-TBOX Deletion produced according to the claimed genus of nucleic acids as broadly as is claimed. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (PNAS, Vol., 79, Pg. 1979, 1982; cited in PTO892; hereinafter “Rudikoff”). Rudikoff teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. While CDR mutation might be expected to alter antigen binding of an antibody, framework mutations can also have an effect. Panka et al. (PNAS, Vol., 85, 1988; cited in PTO892) teach that a single amino acid difference in a framework residue at the boundary with CDR3 was responsible for the decreased affinity of an anti-digoxin antibody (Pg. 3083, Column 1, Paragraph, first partial). Similarly, in regard to the genus of antigen-binding fragments that specifically bind to B7-H6 Zhang et. al (J Immunol (2012) 189 (5): 2290–2299, cited in PTO 892) the ordinary skilled artisan would have been motivated to produce activate the immune cell. In regard to the reasonable expectation of success of substituting a known antigen-binding domain into a CAR, this was a well-known substitution at the time of filing and required no more than simple subcloning and routine recombinant technology.
The quantity of experimentation needed to make or use the invention:
Applicant has claimed a genus of antibody fragment that the recognizes TZ.47 scFv and comprising the amino acid sequence of at least 80-99% identity with Tz.47-28-3z, Tz.47-28-3zMsTBET, Tz.47-28-3zMsTBET-STOP and Tz.47-28-3zMsTBET-TBOX Deletion; however, it only describes in the specification amino acid sequence identity 100%. Because Applicant has no manner a priori to predict which amino acid in the CDR can be modified and used to make TZ.47 antibody fragments, the genus of antibody fragments claimed by Applicant cannot be predictably made or used by the ordinary artisan. Such random experimentation to identify later what structure, variant, or modification is not functional and is embraced by Applicant's claims is undue experimentation. Furthermore, functionally defined genus claims can be inherently vulnerable to invalidity challenges for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
Conclusion:
Taken together, the person of ordinary skill in the art would not have concluded that the applicant possessed the invention as it is claimed. The Examiner concludes that there is an insufficient written description of the instantly claimed genus of an antibody fragment that the recognizes TZ.47 scFv (i.e., B7-H6) and comprising the amino acid sequence of at least 80-99% identity with Tz.47-28-3z, Tz.47-28-3zMsTBET, Tz.47-28-3zMsTBET-STOP and Tz.47-28-3zMsTBET-TBOX Deletion. Specifically, it only describes disclose the amino acid sequence of at least 100% identity. However, it claims broadly amino acid sequence of at least 80-99% identity including the CDR mutation. The Examiner further concludes a skilled artisan would find the specification inadequately described.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claim 50-54, 57-61 and 68 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lim et al. (US20160264665 A1, Pub. Date: Feb. Sep. 15, 2016; cited in IDS filed 10/24/2024; hereinafter “Lim”).
Regarding claims 50-51, 61 and 68, Lim claims a nucleic acid comprises a nucleotide sequence encoding a transcriptional control element, responsive to the transcriptional activator, operably linked to a nucleotide sequence encoding a chimeric antigen receptor (CAR). (Claim 147). The intracellular domain comprising a transcriptional activator (i.e., transcription factor), wherein binding of the scFv or the nanobody to the antigen induces cleavage of the Notch receptor polypeptide at the one or more proteolytic cleavage sites, thereby releasing the intracellular domain comprising the transcription activator (i.e., transcription factor) (claim 144) and the transcriptional factor is T-bet ([0496], Fig, 28, 22 and 16A). Lim further claims that a recombinant expression vector comprising the nucleic acid (claim 164) and a kit comprising the nucleic acid construct [0164].
Regarding Claims 52, 57-58, Lim teaches a nucleic acid comprising (a) a nucleic acid encoding a chimeric antigen receptor (CAR) comprises an antigen binding domain (e.g., an scFv), a transmembrane domain CD28 and intracellular signaling domains CD28 and CD3zeta [0517, 0543].
Regarding claims 53, Lim claims the nucleic acid construct is in an immune cell (Claims 167-170), and as stated above, the transcription activator (i.e., transcription factor) induces (i.e, enhances) the expression of said CAR.
Regarding claim 54, Lim teaches that the CAR comprises a human, humanized, or chimeric antigen binding domain, optionally wherein the antigen binding domain comprises a human, humanized, or chimeric scFv [0139]-[0140].
Regarding claims 59-60, Lim teaches that the nucleic acid encoding the CAR and the nucleic acid encoding the transcription factor are on the same vector or on different Vectors [0546].
Accordingly, Lim anticipates the instant claims 50-54, 57-61 and 68.
Subject matter free of art
Claims 55-56 are objected because art does not teach or reasonably suggest the SEQ ID NOs: 13, 24-26, 34-39 (see ABSS report filed Jul. 17 2026). Since claims 55-56 depend from rejected base independent claim 50. Claim 55-56 would be free of the art, if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached on (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MASUDUR RAHMAN/Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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