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 .
Claims Status
The amendments and remarks filed 06/05/2026 are acknowledged.
Claims 21 and 24-33 are pending.
Claims 1-20 and 22-23 are cancelled.
Claims 21 and 24 are amended.
Claims 33 is new.
Claims 25-32 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 21, 24, and 33 are under examination.
Withdrawn
The objections to the drawings are withdrawn. Applicant has submitted replacement drawings to overcome the objections.
The objection to claim 21 is withdrawn. Applicant has amended the claim to overcome the rejection.
The rejections of claims 21 and 24 under 35 U.S.C. 112(b) are withdrawn. Applicant has amended claim 21 to overcome the rejections.
The rejection of claim 24 under 35 U.S.C. 112(d) is withdrawn. Applicant has amended the claim to overcome the rejection.
The previous rejection of claim 21 under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendment to claim 1 requiring that the amino acid sequence of the anti-CD7 VHH antibody is set forth in SEQ ID NO: 6.
Maintained Rejections
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.
This rejection has been modified solely to address the amendments to claim 21 requiring that the anti-CD7 antibody comprises SEQ ID NO: 6.
Claims 21 and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 11, 13, and 14 of copending Application No. 18/253,819 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 21 and 24, claim 1 of the reference application teaches a method for preparing CD7-CAR-T cells, which comprises the following steps: (i) providing a sample to be processed containing T cells, (ii) sorting and activating the T cells contained in the sample, thereby obtaining activated T cells, (iii) introducing a first viral vector for expressing a CD7-blocking molecule into the activated T cells, thereby obtaining CD7-blocked T cells, and (iv) introducing a second viral vector for expressing a CD7-CAR into the CD7-blocked T cells, thereby obtaining the CD7-CAR-T cells, wherein, after the T cells are co-incubated with an activator for 12-36 h, preferably 18-30 h, more preferably 22-26 h, the first viral vector for expressing a CD7-blocking molecule is introduced into the activated T cells, claim 8 of the reference application teaches wherein the CD7-blocking molecule comprises one or more anti-CD7 nanobodies and an endoplasmic reticulum retention sequence, claim 11 of the reference application teaches wherein the CD7-blocking molecule has a structure as shown in the following Formula II: L’-VHH’-ER (II), wherein, each "-" is independently a linking peptide or peptide bond; L' is a signal peptide sequence; VHH' is a binding region comprising two anti-CD7 nanobodies; and ER is an endoplasmic reticulum retention sequence, claim 13 of the reference application teaches wherein the amino acid sequence of the ER is shown in SEQ ID NO: 10, and claim 14 of the reference application teaches wherein the amino acid sequence of the CD7-blocking molecule is shown in SEQ ID NO: 1 or 2.
SEQ ID NO: 10 of the reference application has 100% sequence identity to SEQ ID NO: 10 of instant claim 21 and SEQ ID NO: 2 of the reference application has 100% sequence identity to SEQ ID NO: 2 of instant claim 24, respectively. Further SEQ ID NO: 2 of the reference application comprises SEQ ID NO: 6, as set forth in instant claim 21. See alignment below.
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments Regarding Double Patenting Rejections
The double patenting rejections over copending Application No. 18/253,819 (reference application) are maintained. On page 12 of the remarks, Applicant argues that the reference application merely recites anti-CD7 nanobodies in a generic manner and does not require the anti-CD7 VHH sequence recited in claim 21. This is not found persuasive because SEQ ID NO: 2 of the reference application, which has 100% sequence identity to SEQ ID NO: 2 of instant claim 24, comprises the anti-CD7 VHH sequence recited in claim 21 (i.e. SEQ ID NO: 6). See sequence alignment above. Thus, the reference application does not merely recite anti-CD7 nanobodies in a generic manner as Applicant argues, but rather, the reference application teaches the exact same sequence as claimed for the CD7-blocking molecule.
Applicant further argues that the reference application is directed to a method for preparing CD7-CAR-T cells, and thus, the reference claims are directed to a specific manufacturing process and do not claim the presently recited molecule having anti-CD7 VHH domains defined by SEQ ID NO: 6. This is not found persuasive because while the reference application may be directed to a method of manufacture, the reference application nonetheless teaches the product produced by the process, more specifically, a CD7-blocking molecule comprising SEQ ID NO: 2, which is identical to the CD7-blocking molecule as instantly claimed, and which comprises a VHH domain identical to instantly claimed SEQ ID NO: 6. See above.
New Grounds of Rejection Necessitated by Amendment
Claim Rejections - 35 USC § 112(b)
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 24 is 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.
Claim 24 recites the limitation “VHH’ is a binding region comprising two anti-CD7 VHH antibodies, and the amino acid sequence of the anti-CD7 VHH antibody is set forth in SEQ ID NO: 6”. Since the claim recites “two anti-CD7 VHH antibodies”, it is unclear what anti-CD7 VHH antibody is being referred to that comprises SEQ ID NO: 6 or if both comprise SEQ ID NO: 6. Therefore, the scope of this claim is indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 33 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 33, which depends from claim 24, recites the limitation of “the nucleic acid molecule according to claim 24, which comprises a sequence as set forth in SEQ ID NO: 1.” SEQ ID NO: 1 is a nucleic acid sequence but depends from a claim requiring a CD7-blocking molecule, i.e. a protein. Therefore, SEQ ID NO: 1 does not further limit the CD7-blocking molecule of claim 24. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Tang et al., 2016 (7/10/2025 IDS) in view of Feldman (WO 2015112830; instant PTO-892), Yang (U.S. Patent No. 10,106,609; instant PTO-892) and Png (US 20180179280; instant PTO-892).
Regarding claim 21, Tang teaches PG002, a bivalent CD7 nanobody-based immunotoxin [see Abstract], comprising two VHH6’s (i.e. two anti-CD7 nanobodies) linked by a flexible linker, with a KDEL (i.e. endoplasmic reticulum retention motif) on the C terminus [see Page 34076; Figure 4A].
However, Tang does not specifically teach that the PG002 comprises a signal peptide on the N-terminus, that the amino acid sequence of the anti-CD7 VHH antibody comprises the amino acid sequence of SEQ ID NO: 6, or that the endoplasmic reticulum retention sequence comprises the amino acid sequence of SEQ ID NO: 10.
Feldman teaches a GM-CSF receptor leader sequence (i.e. signal peptide) that may be positioned at the amino terminus of a polypeptide that may facilitate expression of the polypeptide on the surface of the cell [0021] and CARs comprising an antigen binding domain and can comprise the receptor leader sequence.
Yang teaches a VHH chain of a human CD7 nanobody that can comprise the sequence of SEQ ID NO: 36 [column 2, lines 54-59; columns 23-24, Clone 5 sequence].
SEQ ID NO: 36 of Yang has 100% sequence identity to SEQ ID NO: 6 of the instant claim.
Png teaches compositions comprising an anti-CD7 CAR and an anti-CD7 protein expression blocker [see Abstract] which can comprise a localizing domain linked to the target-binding molecule [0006], and that the localizing domain can be SEQ ID NO: 8, an endoplasmic reticulum (ER) retention peptide [0087].
SEQ ID NO: 8 of Png has 100% sequence identity to SEQ ID NO: 10 of the instant claim.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the bivalent CD7 nanobody-based immunotoxin of Tang to comprise a signal peptide linked to the N terminus of the VHH, as taught by Feldman. One would have been motivated to make this modification because Feldman teaches that the GM-CSF receptor leader sequence can be used for chimeric antigen receptors to facilitate protein expression. It also would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the VHH6 and endoplasmic reticulum retention motif of Tang to specifically be the VHH sequence comprising SEQ ID NO: 36 of Yang and be the ER retention peptide comprising SEQ ID NO: 8 of Png. One would have been motivated to make this modification because Yang teaches that SEQ ID NO: 36 is a VHH chain of a human CD7 nanobody and Png teaches this sequence is a ER retention peptide sequence and can be used in anti-CD7 CARs. Further, one would have been motivated to use these sequences for the VHH and the ER retention sequence because they are known sequences in the art, and it is obvious to use known variations in the prior art for predictable outcomes. See MPEP 2143 (F).
Response to Arguments Regarding Rejections Under 35 U.S.C. 103
The previous rejection of claim 21 under 35 U.S.C. is withdrawn. However, Applicant’s arguments will be addressed to the extent they apply to the newly applied rejection. On pages 7-8, Applicant argues that Tang is directed a fundamentally different molecule serving a fundamentally different purpose than the presently claimed CD7-blocking molecule and that Tang does not disclose or suggest a molecule designed to e.g. intracellularly sequester CD7 and thereby block expression of CD7 on the surface of T cells, nor does Tang recognize the technical problem addressed by the claimed invention, namely the prevention of fratricide during production of CD7-targeted CAR-T cells by blocking expression of CD7 on the CAR-T cells themselves. Applicant further argues that the claimed construct therefore differs from the construct of Tang not merely in structural details but also in intended function and biological activity. This is not found
persuasive because in response to applicant's argument that the references fail to show
certain features of the invention, it is noted that the features upon which applicant relies
(i.e., intracellularly sequester CD7 and prevent fratricide during production of CD7-targeted CAR-T cells by blocking expression of CD7 on the CAR-T cells themselves) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
On pages 8-19 of the remarks, Applicant argues that the present application demonstrates that the claimed CD7-blocking molecule can exhibit the unexpected results of an exceptionally high level of CD7-blocking activity without adversely affecting normal expansion of engineered T cells, altering CD4/CD8 phenotype distribution, and impairing cytotoxic activity against target cells, pointing to Examples 1-4 of the instant specification for support. Applicant further argues that none of the prior art teachings would have led a person of ordinary skill in the art to reasonably expect that the claimed CD7-blocking molecule would simultaneously (1) reduce detectable CD7 surface expression to less than 0.5%, (2) render CD7 expression substantially undetectable in both T cells and CAR-T cells, (3) prevent fratricide-associated loss of engineered cells, (4) permit normal cellular expansion, and (5) preserve phenotype and cytotoxic function of CAR-T cells. This is not found persuasive because in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., (1) reduce detectable CD7 surface expression to less than 0.5%, (2) render CD7 expression substantially undetectable in both T cells and CAR-T cells, (3) prevent fratricide-associated loss of engineered cells, (4) permit normal cellular expansion, and (5) preserve phenotype and cytotoxic function of CAR-T cells) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Further, Example 1 (results shown in Figure 1) do not compare the claimed CD7-blocking molecule to any other CD7-blocking molecules, Example 2 (results shown in Figure 2) does not demonstrate the results of the CD7-blocking molecule alone, Example 3 (results shown in Figure 3) does not demonstrate the results of the CD7-CAR alone, and Example 4 (results shown in Figure 4) does not demonstrate the results of the CD7-blocking molecule alone in Figures 4A and 4B. Therefore, the Examiner cannot make a determination of a trend that would lead to a conclusion of unexpected results. The burden is on Applicant to provide to the Examiner a trend proving the unexpected results. See MPEP 716.02(b). In view of the above, Applicant’s arguments of unexpected results are not persuasive to rebut the 103 rejection.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brittney E Donoghue whose telephone number is (571)272-9883. The examiner can normally be reached Mon - Fri 7:30 - 3:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571) 272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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