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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/26/25 has been entered.
Allowable Subject Matter
Claim 27 is allowed.
Claim 121 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Response to Amendment
Applicant's arguments filed 11/26/25 have been fully considered but they are not persuasive to overcome the rejection of record.
The rejections are maintained for the reasons of record. In the final rejection, the examiner indicated “The arguments regarding the TriPril CAR are strong but no claim contains this limitation. Newly amended claim Claim 1 indicates that the CAR can contain “a portion thereof” which is not commensurate with the unexpected results.”
Applicant argues in conclusion that “Thus, the skilled person would not have had a reason to modify the APRIL CAR of UCL to produce a CAR comprising 3 or more APRIL domains because the produced CAR, based on the teachings of UCL and HHS, (1) would not have brought the signaling endodomains of multiple CARs together to achieve the T cell activation advantages of the trimerized APRIL CARs reported
in UCL, (2) would not have had two independent moieties that recognize distinct highly conserved sites, which HHS proposed as causing greater potency than a monspecific CAR, and (3) the APRIL CAR of ULC already was already bispecific for distinct sites, BCMA and TACI.” However applicant’s arguments are not persuasive for the reasons already of record particularly where applicant’s clams only require “a portion thereof” of the APRIL domain.
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 1-3, 8, 11, 17 23, 32, 34, 44-45, 101 & 119-120 & 122-123 (as they read on the generic invention) are rejected under 35 U.S.C. 103 as being unpatentable over WO 2015/052538 (UCL) and US 2017/0267739 (HHS).
UCL teaches a chimeric antigen receptor (CAR) polypeptide (pg 22, In 16-20) which has a) an extracellular domain, comprising a Tumor Necrosis Factor (TNF) superfamily receptor ligand or a portion thereof, b) a transmembrane domain; and C) an intracellular signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma. UCL teaches wherein the transmembrane domain comprises a hinge/transmembrane domain (p. 3, In 20-30) (from CD28), one or more co-stimulatory domains (p 12, In 26-33), wherein the TNF superfamily receptor ligand is A Proliferation-Inducing Ligand (APRIL) (Abstract) and wherein the composition wherein the portion of APRIL does not comprise a cleavage site (pg 16, In 9-11).
UCL does not specifically teach a CAR with the three targeting domains as is claims however UCL teaches there are three domains in the binding of BCMA with APRIL and targeting of all 3 domains (pg 7, In 11-21) predicting that the three-fold symmetry inherent in the binding of BCMA with APRIL. This means that every interaction between the CAR and BCMA will involve 3 CARs, approximating 3 endodomains on the T-cell surface. Since T-cell activation is triggered by close approximation of signaling endodomains in an immunological synapse, the CAR design of the present invention is highly sensitive and specific
One of ordinary skill in the art at the time the invention was filed would have made a CAR polypeptide as is claimed because HHS teaches wherein a CAR can be designed to have more than one extracellular domain [0122] The CAR molecules disclosed therein include one targeting domain of a multispecific CAR can be a cell surface receptor, such as CD4 (i.e., a multispecific CD4- based CAR). In another example, one targeting domain of a multispecific CAR can be a cell surface receptor, such as CD4, and the second targeting domain can be an antibody or a fragment thereof, such as a scFv (i.e. a multispecific CD4-scFv CAR). Given the teachings of UCL and HHS, it would have been obvious to design a CAR with the 3 extracellular domains that target each binding sights between BCMA and APRIL as taught by UCL using the CAR multiple extracellular domain structure designs of HHS, in order to block all binding between BCMA and APRIL with a single CAR molecule. HHS further teaches wherein the two or more extracellular domains are connected to each other by one or more linker sequences [0006], comprises a leader sequence, wherein the leader sequence is a CDS leader sequence [0258] and wherein he co-stimulatory domain comprises the intracellular domain of 4-1 BB [0259].
Applicant is directed to pages 12-13 of KSR v Teleflex (500 US 398 2007) “ … the Court has held that a “patent for a combination which only unites old elements with no change in their respective functions . . . obviously withdraws what is already known into the field of its monopoly and diminishes the resources available to skillful men.” Great Atlantic & Pacific Tea Co. v. Supermarket Equipment Corp., 340 U. S. 147, 152 (1950). This is a principal reason for declining to allow patents for what is obvious. The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” “When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one(emphasis added). If a person of ordinary skill can implement a predictable variation, §103 likely bars its patentability. For the same reason, if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill.”
"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); >see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.");< ** In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
Accordingly, the claimed invention was prima facie obvious to one of ordinary
skill in the art at the time the invention was made especially in the absence of evidence
to the contrary.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BLAINE LANKFORD whose telephone number is (571)272-0917. The examiner can normally be reached M-Th 8-6:30.
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BLAINE LANKFORD
Examiner
Art Unit 1657
/BLAINE LANKFORD/Primary Examiner, Art Unit 1657