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
Claims 1-16, 18-19 and 21-32 are pending.
Claims 1-13 and 21-32 are withdrawn.
Claims 14-16 and 18-19 are under examination.
Withdrawn Claim Objections
The objection to claim 20 due to informalities as set forth in the previous office action is withdrawn in view of the cancellation of this claim.
New Claim Objections
Claim 14 is objected to because of the following informalities:
Claim 14 recites “and introduction of the nucleic acid into the T cells by the nucleic acid delivery carrier” which is grammatically improper because it is missing a verb.
Appropriate correction is required.
Withdrawn Claim Rejections - 35 USC § 112(a)
Scope of Enablement
The rejection of claims 14-16 and 18-19 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph because the full scope of the claims is not enabled is withdrawn in view of Applicant’s amendments.
The rejection of claim 17 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph because the full scope of the claims is not enabled is withdrawn in view of the cancellation of this claim.
Withdrawn Claim Rejections - 35 USC § 112(b)
The rejection of claims 14-16 and 18-19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of Applicant’s amendments.
The rejection of claims 17 and 20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of Applicant’s amendments.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 14-16 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Sahin et al. (WO-2016/180778-A1; henceforth “Sahin”).
Regarding claim 14, Sahin discloses a method for delivering a nucleic acid into T cells, comprising a step of contacting a cell population containing T cells (splenocytes) with at least one kind of T cell activating ligand (anti-CD3 and anti-CD28; pg. 67-68), and subsequently contacting the cell population with a nucleic acid delivery carrier containing a nucleic acid inside in one pod (well) (MLV-E retroviral vector with CLDN6-CAR; pg. 67-68) (see also Figure 5; Example 1).
Regarding claim 14, Sahin discloses the nucleic acid delivery carrier can be a liposome (“the nucleic acid encoding the antigen or variant thereof is formulated in liposomes” pg. 7 3rd para. ; see also pg. 38, 40-41, 68, 70; Claim 25).
Regarding the negative proviso of claim 14, Sahin is silent to a T cell activating ligand added to the surface of the liposome and therefore the liposome is free of a T cell activating ligand added to its surface.
However, regarding claim 14, Sahin does not disclose activation/proliferation of T cells by the T cell activating ligand and introduction of the nucleic acid into T cells by the nucleic acid delivery carrier are simultaneously performed.
Nevertheless, regarding claim 14, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Sahin, and choose simultaneous activation from the finite number of two solutions of simultaneous activation and subsequence activation (pre-activation of Sahin). Regarding the reasonable expectation of success, instant claims only require introducing the nucleic acid in to the T cell. Since liposomes can transfect cells in the absence of T cell activation, one of ordinary skill would have had a reasonable expectation of success in introducing the nucleic acid into at least one cell.
Furthermore, regarding claim 14, simultaneous activation is a timing of a step. Therefore, one of ordinary skill would not consider optimization of the timing of the activation step to be inventive.
Applicant is reminded that generally, differences in timings will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such timing is critical (MPEP 2144.05 II).
Regarding the wherein clause of claim 14, it is noted that the wherein clause does not recite any additional active method steps, but simply state a characterization or conclusion of the results of process step positively recited (e.g. “the T cells are activated/proliferated by the T cell activating ligand and introduction of the nucleic acid into the T cells by the nucleic acid delivery carrier”). Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."). See also MPEP 2111.04 which states that a “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure” and a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.”
Furthermore, regarding claim 14, the active method steps of the instantly claimed method are made obvious by Sahin above and therefore the result of “the T cells are activated/proliferated by the T cell activating ligand and introduction of the nucleic acid into the T cells by the nucleic acid delivery carrier” would naturally follow the recitation of the taught steps.
Regarding claim 15, further to the discussion of claim 14 above, Sahin discloses the T cell activating ligand includes an antibody to CD3 and/or an antibody to CD28 (anti-CD3 and anti-CD28; pg. 67-68).
Regarding claim 16, further to the discussion of claim 14 above, Sahin discloses two or more kinds of T cell activating ligands are contacted (anti-CD3 and anti-CD28; pg. 67-68).
Regarding claims 18 and 19, further to the discussion of claim 14 above, Sahin discloses the nucleic acid nucleic acid encodes a T cell activation promoting factor (claim 18), which is a CAR (claim 19) (CLDN6-CAR; Figures 4-8; pg. 64-68, 70-71; Example 1).
Hence, the claimed invention as a whole was prima facie obvious.
Response to Arguments
Applicant’s arguments, filed 14th, August, 2025, have been fully considered but are not found persuasive.
Applicant argues unexpected results (pg. 7). Specifically, Applicant argues “If T cells are simultaneously contacted with a T cell activating ligand and a nucleic acid delivery carrier that does not contain said ligand, a person skilled in the art would normally expect that, although T cells would be activated by the T cell activating ligand, the efficiency of nucleic acid delivery into T cells by the nucleic acid delivery carrier would be reduced (due to the lack of surface modification of the nucleic acid delivery carrier). However, as shown in the examples of the present application, when T cells are simultaneously contacted with a T cell activating ligand and a nucleic acid delivery carrier that does not contain said ligand, the T cells are activated and exhibit high transduction efficiency, which is a surprising result. This constitutes a separate unexpected that directly results from use of the nucleic acid delivery carrier "without surface modification" of the nucleic acid delivery carrier “ (pg. 7). Applicant further argues that the claims as amended are commensurate in scope with the alleged unexpected results (pg. 8).
First, in response, arguments of counsel cannot take the place of factually supported objective evidence in the record. See In re Schulze, 346 F.2d 500, 602, 145 USPQ 716, 718 (CCPA 1965), In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Thus, Attorney statements regarding the alleged unexpected result (i.e., “high transduction efficiency” pg. 7) are not evidence without a supporting declaration.
Further in response, the alleged unexpected results are not commensurate in scope with Applicant’s claims. Applicant’s specification evidences two specific examples encompassed by the claimed method (Examples 15-16) which are described as “highly efficient.” Example 15 uses CD3/CD28 DynabeadsTM, and Example 16 uses TransActTM which has CD3 and CD28 agonists. The use of these specific T-cell activating ligand products is not commensurate in scope with the instantly claimed method which only requires “at least one kind of T cell activating ligand.” Furthermore, the CD3/CD28 DynabeadsTM and TransActTM which has CD3 and CD28 agonists. Each of these producers comprise two-specific T-cell activating ligands (CD3 and CD28 agonists) in close proximity and these provide co-stimulation that results in T-cell activation. This is a much more specific embodiment than “at least one kind of T cell activating ligand.” Applicant has not provided factually objective evidence on the record that the full breadth of the claims achieves the alleged unexpected result with a reasonable expectation of success.
Applicant is reminded that DynabeadsTM and TransActTM are trademarked products and are not allowed in claims (see MPEP 2173.05(u)).
Conclusion
No claim is allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANA N EBBINGHAUS whose telephone number is (703)756-4548. The examiner can normally be reached M-F 9:30 AM to 5:30 PM ET.
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632