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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/27/2026 has been entered.
Election/Restrictions & Priority
Applicant’s election without traverse of Group I, claims 32-48, and election of species: SEQ ID NO. 693 for claim 38, in the reply filed on Aug 13, 2024, previously acknowledged, continues to be maintained. Claims 49-51 were withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected groups, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/13/2024.
This application benefits from the priority date of the foreign application EP17181798.4, which is 07/18/2017.
Status of the Claims
Claims 32-38 and 40-48 are being examined.
Amendments
This action is in response to papers filed 27th Jan 2026, in which claim 32 was amended with the recitation from previous claim 39 and claim 39 was canceled, and no new claims were added. All of the amendments have been thoroughly reviewed and entered.
Applicant’s arguments, see Pgs. 9 - 10, filed 27th Jan 2026, with respect to:
rejections of claims 32-38, 40-44, and 47-48 under 35 USC § 103 have been fully considered but are not persuasive for the reasons discussed in this office action. Applicant’s amendments have overcome the 103 rejections over Engler and Coren in view of others. The 103 rejections in the previous office action are withdrawn. However, the claims are still not free of the prior for the reasons recited in the rewritten §103 rejections below addressing amendments.
NSDP rejections of claims 32-37, 40-41, 43, and 47-48 are not persuasive for the reasons discussed in this office action; the NSDP rejections of claims 32-37, 40-41, 43, and 47-48 are maintained; while the NSDP rejections of claims 38, 42, and 44-46 are persuasive and the rejection of these claims is withdrawn.
Any rejection or objection not reiterated herein has been overcome by amendment.
Arguments applicable to maintained rejections are addressed below. Arguments that are no longer relevant are not addressed.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 32-38 and 40-48 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
This is a new rejection necessitated by amendment.
Regarding claim 32, the newly amended phrase " the J donor vector comprises an oligonucleotide having the sequence of SEQ ID NO: 700 "and the previously recited phrase (B) the J donor oligonucleotide sequence further comprises: a. an origin of replication, b …e… in claim 32 render the claim indefinite because it is not clear if the elements a to e as recited are encompassed in the sequence of SEQ ID NO: 700. The specification in Fig. 4E and examination of the sequence itself indicates that Type IIS sequences are part of the 13 nucleotides that make up SEQ ID NO: 700. However, it is not clear if any other of the recited elements are also part of SEQ ID NO: 700 or in addition to it. Thus, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Clarification is required.
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 32-37, 40-41, 43, and 47-48 are rejected under 35 U.S.C. 103 as being unpatentable over Schendel (WO 2016/193299, IDS of 10/14/2021) in view of Engler (Engler et al., (2008), PloS one, 3(11), e3647) and Katzen (US 20130274129 A1) and evidenced by Addgene (pUC19 plasmid vector sequence and map, 2002) (claim 32).
This is a new rejection necessitated by amendment.
Regarding claim 32, Schendel teach a TCR library system that allows for fast reconstruction of TCR sequences and enables unrestricted exchange of TCR sub-domains. The system is modular having different building blocks that makes it possible to exchange the different TCR regions (variable, constant, CDR3) (pg. 2). The library comprises 45 TCR constructs each encoding one of the 45 different variable TCR a chains and 47 TCR constructs each encoding one of the 47 different variable TCR b chains, each integrated into one backbone vector individually (pg. 4).
Schendel ’s constructs read on instant oligonucleotide sequences (A) and (B) as further described:
Each of the TCR constructs encoding the variable TCR a chain comprises (i) one of the variable AV segments; (ii) a linker sequence specific for the A segment. Each of the TCR constructs encoding the variable TCR b chain comprises (i) one of the variable BV segments; (ii) a linker sequence specific for the B segment (pg. 66). The segments are further designed to be easily exchanged. See following recitation from Schendel (pg. 5):
To achieve this, the building blocks contain at least one combination site at the 5 '-end and at least one combination site at the 3 '-end. More specifically, the combination site of the 3 '-end of a first building block is compatible to the combination site at the 5 '-end of the second building block which may be connected to the 3 '-end of the first building block.
Schendel ’s vectors read on instant vectors (I) and (II) as further described:
Schendel teach constructs may be integrated into the backbone vectors by known cloning techniques that include use of Type IIS restriction enzyme based cloning approaches, use of recombination based cloning approaches such as Gateway® cloning and others (pg. 66) and describe making of their vector library using a retroviral vector backbone (pg. 72). Schendel teach various components are part of vectors. See the recitation from pg. 41:
Expression vectors typically contain one or more of the following components (if they are not already provided by the nucleic acid molecules): a promoter, one or more enhancer sequences, an origin of replication, a transcriptional termination sequence, a complete intron sequence containing a donor and acceptor splice site, a leader sequence for secretion, a ribosome binding site, a polyadenylation sequence, a polylinker region for inserting the nucleic acid encoding the polypeptide to be expressed, and a selectable marker element.
Schendel ’s vectors are constructed in such a way that each segment or segment variation (variable V, linker sequence and constant C segment) can be easily exchanged in a single step procedure (pg. 5). Also see Fig. 1. Schendel further teach how the various components come together to make a complete TCR, see Fig. 9A-B.
Thus, Schendel ’s AV segment containing vector reads on instant vector comprising VC oligonucleotide and Schendel ’s vector comprising linker reads on instant J donor vector comprising J segment. Specifically, Schendel ’s teaching of an origin of replication reads on instant a. an origin of replication; Schendel ’s teaching of a donor and acceptor splice site reads on instant c. a 5' genetic element, and a 3' genetic element; and Schendel ’s teaching of Type IIS restriction enzyme based cloning approaches reads on instant, e. a first Type IIS recognition sequence and g. a second Type IIS recognition sequence.
Schendel lack a teaching on:
the J donor vector comprises an oligonucleotide having the sequence of SEQ ID NO: 700.
the oligonucleotide sequence comprising e. a Kozak sequence
specifics of vector selectable marker elements b. a first positive selection marker and f. a negative selection marker
the location of the various components; i.e., wherein the TCR variable gene segment is flanked by the Kozak Sequence on one end and the first Type IIS recognition sequence on the other end, and wherein the TCR constant gene segment is downstream of the second Type IIS recognition sequence and upstream of the 3' genetic element
However, before the effective filing date of instant invention, Engler had taught Golden Gate cloning approach that capitalizes on the unique feature of Type IIS restriction enzymes Engler teach Golden Gate comprising: at least two entry vectors into which any gene segment may be inserted (Fig.3B) and a destination vector that allows for the combination of entry vector elements (Fig.3A). Engler base their vectors on the pUC19 plasmid. As evidenced by the vector sequence and map (shown below), pUC19 has a. an origin of replication.
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Engler’s vectors further comprise: b. a first positive selection marker (S2, Fig. 3A), c. a 5' genetic element (grey triangle represents an attB recombination site; Fig. 3A), e. a first Type IIS recognition sequence (box labeled B in Fig. 3B), f. a selection marker (box labeled Z in Fig. 3A), g. a second Type IIS recognition sequence (box labeled B in Fig. 3B), and h. a 3' genetic element (box labeled N which is a viral 3′ non-translated region). Engler teach the restriction sites on the entry and recipient vectors are Bsa1 restriction sites. See Fig. 1, also below, for the sequence.
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By alignment, instant SEQ ID NO: 700 comprises this same (Bsa1) sequence of Engler as shown in bold below:
1 GAATTCGGTCTCG 13
Engler’s Golden Gate system is particularly advantageous because the use of Type IIS recognition sequences allows for cleavage to occur outside of the recognition site, resulting in overhangs that can consist of any nucleotide (pg. 1, last line). When combined, the entry vectors and destination vector together form a vector wherein the gene of interest (GFP) is retained and the selection marker is spliced out (lower vector in Fig. 3B). Engler’s Fig. 3A and B shown below:
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Thus, it is inherent in Engler’s Golden Gate system wherein the gene or fragment to be inserted (instant TCR variable gene segment) is positioned after the 5’ genetic element on one end and the first Type IIS recognition sequence on the other end, and wherein the second gene or fragment to be inserted (instant TCR constant gene segment) is downstream of the second Type IIS recognition sequence and upstream of the 3' genetic element.
Engler lack a teaching on (A) the VC oligonucleotide sequence further comprises: … f. the selection marker is a negative selection marker and the oligonucleotide sequence comprising a Kozak sequence.
However, before the effective filing date of instant invention, Katzen had reduced to practice the use of Golden Gate to code for coding multiple functional components (abstract, [0370]). Katzen had taught creation of libraries, using the Golden Gate technique of Engler, comprising vectors which encode functional proteins [0039]. Katzen taught, the Golden Gate strategy, which permits the generation of libraries of recombinant genes by combining in one reaction several fragment sets prepared from different parental templates, is also useful for building highly repetitive nucleic acid molecules [0370]. Katzen’s vectors comprise a negative selection marker juxtaposed between two compatible type IIS restriction enzyme cleavage sites such that insertion of the gene segment of interest into the vector will result in elimination of the negative selection marker [0058]. See recitation from Katzen:
“target vector via compatible type IIS restriction enzyme cleavage sites thereby replacing a negative selection marker gene”.
Further, Katzen describe the negative selection marker as being “toxic or otherwise inhibitory” to the cells [0120-0121]. Further, Katzen describe in [0125] that any vector can be modified to include a negative selection marker (counter selectable marker). See recitation from that para:
“Any of the vectors used in embodiments of the invention (including cloning vectors, expression vectors, capture vectors, viral vectors or functional vectors) can be modified to carry counter selectable marker genes such as ccdB or tse2 or functional variants thereof”.
In [0119] Katzen state that selectable markers (positive and negative) are widely used as reporter systems in genetic engineering to evaluate the success of cloning strategies or cell transduction efficiency. See Katzen’s vectors carrying both a positive (pos sel) and negative selection (neg sel) marker:
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In [0280] Katzen state that Kozak consensus and polyA signal are generally provided on the RNA.
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to utilize the Golden Gate method of Engler in cloning components of the TCR for the advantage of using Type IIS recognition sequences, which in turn allow for efficient assembly of multiple fragments of DNA as needed for TCR, and further substituting the selection marker for a negative selection marker as demonstrated by Katzen. One skilled in the art knows that TCRs consist of highly repetitive regions such as the constant chains, and so would be especially motivated to use Engler’s Golden Gate because Katzen teach that Golden Gate is especially useful in situations where there are highly repetitive nucleic acid molecules. Further, substitution of a negative selection marker in place of Engler’s marker would be a simple substitution because Katzen states that use of selection markers is a common genetic engineering technique. By using the BsaI as the Type IIS recognition sequence, as taught by Engler, one would have a sequence sufficiently similar to instant SEQ ID NO: 700, to use as the means of joining the various components. See MPEP 2144, 2143 I.(A) and (B).
Regarding claims 33 and 35, the vector system of claim 32 is discussed above. As discussed for claim 32, Schendel teach their vector comprises 5' and 3' genetic elements that are homologous recombination arms for a genomic site of interest (pg. 5, 2nd para). See also last para of pg. 59.
Regarding claim 34, the vector system of claim 32 is discussed above. Schendel further disclose their vector comprises selection markers. Engler also teach on page 6, right- hand column, second paragraph that the negative selection marker can be: any other negative selection marker that an experimenter would prefer to use. Katzen’s teachings of negative selection markers have been discussed for the rejection of claim 32 and similarly apply here (Katzen, [0119] and [0120-0121]).
Regarding claims 36 and 37, the vector system of claim 32 is discussed above. Schendel further disclose CDR3 duplex oligonucleotides are part of a vector system encoding the TCR segments (Fig. 9A and 9B). The duplexes are flanked by linker segments (thin line in figures). The linker segments are restriction endonuclease sites (NotI, AgeI, EcoRI; Fig. 10A).
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Regarding claim 40, the vector system of claim 32 is discussed above. As discussed for claim 32, Schendel taught the T cell receptor (TCR) variable gene segment is a TCRα variable gene segment (45 different variable TCR α chains; pg. 3).
Regarding claim 41, the vector system of claim 32 is discussed above. Engler further disclose their vector system comprises a second selection marker (S1; Fig. 3B) and give free reign on selecting a negative selection marker (pg. 6, right- hand column, second paragraph: the negative selection marker can be any other negative selection marker that an experimenter would prefer to use); As discussed for claim 32, Schendel disclose the VC oligonucleotide sequence can be cloned using Type IIS restriction sequences; and Katzen teaches the vector system (Golden Gate/Engler’s) can comprise any number of repeats of vectors, each with selectable markers flanked by Type IIS recognition sequences (Fig. 7B, [0443]).
Regarding claim 43, the vector system of claim 32 is discussed above. Katzen have reduced to practice the use of the Golden Gate vector system of Engler to clone multiple components and Schendel have already taught for TCR these components are Vα and Vβ (45 different variable TCR α chains…47 different variable TCR β chains; pg. 3). Engler further disclose their vector system comprises another entry vector with the same components as the entry vector described in claim 40 except for the gene of interest (box labeled SP is the new gene of interest; Fig. 3C as shown below). Engler also disclose that vectors (constructs) are made by cloning PCR fragments into basic plasmid vectors (Engler, bridging pgs. 6-7).
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Regarding claim 47, the vector system of claim 32 is discussed above. Engler further disclose a second system (consisting of using a second type IIs enzyme to perform the cloning from entry clone to expression vector…in a second set of expression cloning vectors; Pg. 6, 2nd column, 1st paragraph) is possible.
Regarding claim 48, the vector system of claim 43 is discussed above. Engler further disclose a second system (consisting of using a second type IIs enzyme to perform the cloning from entry clone to expression vector…in a second set of expression cloning vectors; Pg. 6, 2nd column, 1st paragraph) is possible.
Thus, Schendel in view of Engler and Katzen make obvious instant claims 32-37, 40-41, 43, and 47-48.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Response to Arguments:
Applicant's arguments filed 01/27/2026 to claim rejections under 35 USC § 103 have been fully considered but they are not persuasive as discussed below.
A. On Pgs. 8-9 of the Remarks, Applicant disagrees with the obviousness over Engler in view of Coren rejection of claims 32-35, 40, 41, 43, 47 and 48 because amended claim 32 recites the J donor vector comprises an oligonucleotide having the sequence of SEQ ID NO: 700, and:
i. Coren does not teach or suggest encoding a J donor oligonucleotide into a vector.
ii. Examiner's interpretation impermissibly expands Coren beyond its actual disclosure, which teaches away from the presently claimed Architecture.
iii. Modifying Coren to encode a J donor oligonucleotide into its own vector would:
• reintroduce the very complexity Coren sought to avoid,
• eliminate Coren' s reliance on direct amplification,
• negate the streamlined, single-step principle of operation, and
• fundamentally redesign Coren' s system.
Such a modification constitutes a change in the principle of operation and therefore cannot support a prima facie case of obviousness. See In re Ratti, 270 F .2d 810 (CCPA 1959).
Regarding A, this argument is moot because instant rejection addressing amendments do not rely on Coren.
B. On Pg. 10 of the Remarks, Applicants go on to critique Studley that was referenced in the previous response to arguments.
Regarding B, this argument is not persuasive. Studley was only used in the Response to Arguments to indicate that it would have been obvious to one of skill in the art to put the PCR-amplified TCR segments into an entry vector, as Studley, a graduate student, had done so relying entirely on the reference of Coren.
C. On Pg. 10 of the Remarks, Applicant disagrees with the obviousness over Engler in view of Coren rejection of claims 32-35, 40, 41, 43, 47 and 48 because previously presented claim 32 comprises the following not taught by the secondary reference of Katzen:
Katzen does not teach a J donor vector nor does it disclose the claimed combinatorial architecture.
Regarding C, this is not persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
D. On page 11, Applicant argues that Schendel does not resolve the deficiency of Engler in view of Coren in the rejection of claims 36-37 because:
Schendel does not teach a J donor vector. Schendel discloses CDR3 duplex oligonucleotides are part of a vector system encoding the TCR segments.
Regarding D, this is not persuasive. The same response as in C. above applies.
E. On pages 11-12, Applicant argues that Liu does not resolve the deficiency of Engler in view of Coren in the rejection of claim 45.
This is not found persuasive because: Applicant does not provide any reasoning for this argument other than its dependency from claim 32. However, in view of the rejection presented in instant office action, Liu is not relied upon as no motivation could be gleaned from the prior art to combine Schendel with Liu.
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 32 – 37, 40-41, 43, and 47-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-10 of U.S. Patent No. US 11274309 in view of Engler (Engler et al., (2008), PloS one, 3(11), e3647) and evidenced by Addgene (pUC19 plasmid vector sequence and map, 2002) (claim 32). See comparison of instant claim 32 and reference claims 4 and 5:
Instant Claim
Reference (US 11274309) Claims
32: A vector system comprising:(I) a variable-constant (VC) entry vector comprising a VC oligonucleotide sequence comprising a T cell receptor (TCR) variable gene segment and a TCR constant gene segment; and(II) a joining donor (J donor) vector comprising a J donor oligonucleotide sequence comprising a TCR joining gene segment, wherein the J donor vector comprises an oligonucleotide having the sequence of SEQ ID NO: 700, wherein:(A) the VC oligonucleotide sequence further comprises: a. an origin of replication, b. a first positive selection marker c. a 5' genetic element, d. a Kozak Sequence, e. a first Type IIS recognition sequence, f. a negative selection marker, g. a second Type IIS recognition sequence, and h. a 3' genetic element, wherein the TCR variable gene segment is flanked by the Kozak Sequence on one end and the first Type IIS recognition sequence on the other end, and wherein the TCR constant gene segment is downstream of the second Type IIS recognition sequence and upstream of the 3' genetic element; and(B) the J donor oligonucleotide sequence further comprises: a. an origin of replication, b. a second positive selection marker, c. a third Type IIS recognition sequence, d. a 5' portion of a constant gene segment, and e. a fourth Type IIS recognition sequence, wherein the TCR joining gene segment is flanked by the third Type IIS sequence on one end and the 5' portion of the constant gene segment on the other end.
4: The two-part device of claim 1, wherein the V-C entry vector component 1A comprises: (a) an origin of replication, (b) a first positive selection marker, (c) one or more 5′ genetic elements, (d) a Kozak Sequence, (e) a TCR variable gene segment, (f) a first Type IIS sequence, for site specific recognition and cleavage by a Type IIS restriction enzyme, (g) a negative selection marker, (h) a second Type IIS sequence, (i) a TCR constant gene segment, and (j) one or more 3′ genetic elements.
5: The two-part device of claim 4, wherein the J donor vector component 1B comprises: (a) an origin of replication, (b) a second positive selection marker, (c) a third Type IIS sequence, (d) a TCR Joining gene segment, (e) a C part, corresponding to a small 5′ portion of a constant gene segment, and (f) a fourth Type IIS sequence.
Thus, claims 4 and 5 of ref. US11274309 are drawn to a first part of a multicomponent T cell receptor (TCR) open reading frame (ORF) reconstitution and engineering system (TORES) that encompasses all the limitations of the instant application as claimed in claim 32.
Patented app claims lack a teaching on SEQ ID NO: 700.
However, before the effective filing date of instant invention, Engler (Engler et al., (2008), had taught the Golden Gate cloning method that is a Type II S restriction enzyme cloning strategy. Engler specifically taught the BsaI Type II S restriction enzyme and provided its sequence. Instant SEQ ID NO: 700 comprises this sequence. Teachings of Engler are discussed in the §103 rejection above.
It would have been obvious to one of ordinary skill, in the art at the time, to modify the patented claims 4 and 5 to include SEQ ID NO 700 as the skilled artisan would have predicted that SEQ ID NO: 700 comprises the restriction enzyme sequences needed to carry out cloning according to Engler’s Golden Gate cloning method. It would have amounted to a simple combination of prior art elements. The skilled artisan would have been motivated to do so for the advantage of carrying out cloning of various components of a T-cell receptor, many of which are known to be repetitive, as Engler’s teachings indicate that the Golden Gate system is specifically designed for the purpose of multi-component cloning. Thus the various limitations of instant claims 32 – 35, 40, 41, 43, 47, and 48 can be reached by combining the patented app claim’s 4-5 and dependent claims 6-10 with Engler.
Response to Arguments:
Applicant's arguments filed 1/27/2026 regarding the nonstatutory double patenting rejections of claim 32 as being unpatentable over claims of U.S. Patent No. 11274309 (reference application) is unpersuasive. The response asserts that the reference claims require the presence of a multicomponent engineered TCR-presenting cell system (eTPCS); i.e., claim 1 of the reference application.
This is not persuasive because:
Instant claim 32 is Part 1 of a 2-part invention (reference application). Part 1 has separate and independent utility from the 2-part invention of the reference application. So, even if the reference application’s claims 4 and 5 require reference application’s claim 1, as Applicants argue, reference application’s claims 4 and 5 can independently anticipate instant independent claim 32 and dependent claims 32-37, 40-41, 43, and 47-48.
Thus, the one-way test for double-patenting has been met.
Therefore, the double patenting rejection is maintained.
Regarding claims 38,42, and 44-46, the claims encompass sequences: SEQ ID NOs: 693 (claim 38), 756 (claim 42), 764 (claim 44), and 777 (claim 46), which are not recited in the claims of the patented application, nor could they be found in the prior art. Therefore, the NSDP rejection of these claims is withdrawn.
Allowable Subject Matter
Claims 38, 42, and 44-46 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The claims encompass sequences: SEQ ID NOs: 693 (claim 38), 756 (claim 42), 764 (claim 44), and 777 (claim 46), which are free of the prior art of record. Additionally, no motivation could be gleaned from the prior art to combine the vector system made obvious with the references applied in the §103 rejection above with a bidirectional terminator donor (BiT donor) vector as recited in claim 45.
Conclusion
Claims 32-38 and 40-48 are rejected.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHABANA MEYERING, Ph.D. whose telephone number is (703)756-4603. The examiner can normally be reached M - F: 9am to 5pm EST.
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SHABANA S. MEYERING, Ph.D.
Examiner
Art Unit 1635
/SHABANA S MEYERING/ Examiner, Art Unit 1635
/CATHERINE KONOPKA/ Primary Examiner, Art Unit 1635
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