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 1-3, 5-11, 13-16 and 19-20 are pending.
Claims 13-16 are withdrawn.
Claims 1-3, 5-11 and 19-20 are under examination.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 19th, November, 2025 has been entered.
Examiner’s Remark
It is noted that Applicant’s amendment, filed 19th, November, 2025 encompasses a switch from the previously elected invention, drawn to a polynucleotide, to a T-cell comprising a polynucleotide. There are no longer any claims drawn to the previously elected polynucleotide group. Applicant is directed to MPEP 819 which states that while applicant, as a matter of right, may not shift from claiming one invention to claiming another, the examiner is not precluded from permitting a shift. The examiner is most likely to do so where the shift results in no additional burden, and particularly where the shift reduces work by simplifying the issues (MPEP 819).
Although this amendment represents an invention switch, it has been entered at the discretion of the Examiner because it appear to result in no additional burden.
Rejoinder
The restriction requirement between Group I, drawn to polynucleotides and expression vectors, and Group II, drawn to immune cells , as set forth in the Office action mailed on 21st, March, 2024 has been reconsidered in view of Applicant’s amendments. Claims 7-11, directed to previously non-elected Group II are no longer withdrawn from consideration.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Duplicate Claim Warning
Claims 2 and 3 appear to be substantially duplicate claims.
Applicant is advised that should claim 2 be found allowable, claim 3 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Withdrawn Claim Rejections - 35 USC § 112(a)
The rejection of claims 1-6 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 as set forth in the previous office action because the amendment filed on 16th, April 2024 contained limitations that appeared to be new matter is withdrawn in view of Applicant’s amendments.
The rejection of claims 4 and 17-18 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 as set forth in the previous office action because the amendment filed on 16th, April 2024 contained limitations that appeared to be new matter is withdrawn in view of the cancellation of these claims.
Withdrawn Claim Rejections - 35 USC § 112(a)
The rejection of claims 1-2 and 5-6 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 as set forth in the previous office action us withdrawn in view of Applicant’s amendments.
The rejection of claims 4 and 17 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 as set forth in the previous office action us withdrawn in view of Applicant’s amendments as set forth in the previous office action is withdrawn in view of the cancellation of these claims.
Withdrawn Claim Rejections - 35 USC § 112(b)
The rejection of claims 1-2 and 5-6 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
The rejection of claims 4 and 17-18 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite as set forth in the previous office action is withdrawn in view of the cancellation of these claims.
Withdrawn Claim Rejections - 35 USC § 103
The rejection of claims 4 and 17-18 as being unpatentable over Galetto et al. (US-2016/0145337-A1; henceforth “Galetto”) in view of Molina et al (WO-2013144409-A2; see IDS filed 1st, September, 2021; pages refer to attached translation; henceforth “Molina”) and Frecha et al. (Gene Ther. 2008 Jun;15(12):930-41.; see IDS filed 1st, September, 2021; henceforth “Frecha”) as set forth in the previous office action is withdrawn in view of the cancellation of these claims.
Claim Rejections - 35 USC § 103
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.
Claims 1-3, 5-11 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Galetto et al. (US-2016/0145337-A1; henceforth “Galetto”) in view of Molina et al (WO-2013144409-A2; see IDS filed 1st, September, 2021; pages refer to attached translation; henceforth “Molina”) and Frecha et al. (Gene Ther. 2008 Jun;15(12):930-41.; see IDS filed 1st, September, 2021; henceforth “Frecha”).
Regarding claim 1, Galetto discloses a T-cell that comprises an expression vector (“TCR-alpha Inactivated Cells Expressing a 4G7-CAR,” “T cells were transduced with a lentiviral vector encoding 4G7-CAR” and “cells transduced with the lentiviral vector encoding 4G7-CAR”; see Example 1; see also (para. [0029]; Claim 8) comprising a polynucleotide comprising a nucleotide sequence encoding a specific chimeric antigen receptor (CAR) and a promoter (para. [0028-0030, 0033-0034, 0039, 0041, 0081]; claims 8 and 20-21) wherein said promoter is operably linked to the nucleotide sequence encoding the CAR in order to drive the expression of the chimeric antigen receptor, and wherein the CAR comprises at least one extracellular ligand binding domain, a transmembrane domain, and at least one intracellular signalling domain (para. [0006, 0016, 0018, 0020, 0025, 0027, 0039, 0086]; see also claims 1 and 11).
However, regarding claim 1, although Galetto discloses a promoter, Galetto does not disclose the promoter is a promoter from the Wiskott-Aldrich syndrome locus, which is a nucleotide sequence comprising SEQ ID NO: 1.
Nevertheless, regarding claim 1, Molina teaches a promoter from the Wiskott-Aldrich syndrome locus, which is a nucleotide sequence comprising SEQ ID NO: 1 (the WAS promoter contained within SEQ ID NO: 4 of Molina comprises both instant SEQ ID NO:1 and instant SEQ ID NO: 2) (see claim 4; pg. 6, 10). Molina teaches the promoter comprises a 387 bp fragment of the alternative WAS promoter immediately upstream of the 500 bp proximal promoter of the WAS promoter (pg. 6)
Additionally, regarding claim 1, Frecha teaches a vector comprising a 386-bp fragment of the alternative WAS promoter immediately upstream of the 500 bp proximal WAS promoter (pg. 6) (Figure 2A; see also pg. 932). Frecha teaches the performance of a vector comprising the alternative WAS promoter immediately upstream of the proximal WAS promoter supported high expression in human T cells, and was a suitable LV backbone for gene therapy of hematopoietic diseases (abstract; pg. 930).
Therefore, regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare the T -cell of Galetto, and simply substitute the known element of the promoter from the Wiskott-Aldrich syndrome locus comprising instant SEQ ID NO: 2 of Molina for the known element of the T7 promoter of Galleta to obtain the predictable result of a T cell that comprises and expression vector (see MPEP 2143 Exemplary Rationale (B). One of ordinary skill would have been motivated to do so as taught by Frecha because a vector containing the alternative WAS promoter immediately upstream of the proximal WAS promoter supported high expression in human T cells, and is a suitable LV backbone for gene therapy of hematopoietic diseases (abstract; pg. 930) and would therefore be beneficial to the vector of Galetto, which is designed to be expressed in human T cells for gene therapy (para. [0002, 0004, 0020-0023, 0025, 0040, 0043-0045, 0051, 0059, 0064, 0083, 0085, 0091-0092, 0103]; Examples 1-3). Regarding the reasonable expectation of success, Molina evidences a vector comprising the promoter and a nucleic acid of interest (Molina SEQ ID NO: 4; claim 4; pg. 6, 10), and Galetto evidences a vector comprising a polynucleotide encoding a CAR and a promoter (Figures 1-6; Example 3). Given that replacing promoter DNA sequences of a vector nucleotide for expression in a T-cell was within the skill level of one of ordinary skill in the art before the effective filing date of the claimed invention, Molina and Galetto together provide a reasonable expectation of success to substitute the promoter.
Regarding the wherein clause of claim 1, this clause recites “an expression profile of the CAR mimics a T-cell receptor (TCR)-like expression pattern” this result appears to be an obvious result of the combination discussed above. First, the instant specification does not provide a special definition of the term “mimic” and therefore it is interpreted as its plain and ordinary meaning of to imitate or copy. The expression pattern of the CAR taught by Galetto is on the surface of the T-cells which is similar to the expression pattern one of ordinary skill would expect of a T-cell receptor and therefore one of ordinary skill would also expect a similar expression pattern. Furthermore, Molina teaches expression vectors comprising the 387 bp fragment 100% identical to SEQ ID NO: 1 as the promoter expressed the transgenes in hematopoietic cells (pg. 6; 6th-7th para), and therefore one of ordinary skill would expect this promoter to similarity express the CAR in the suggested combination above. Finally, Frecha specifically teaches insertion of a 386-bp fragment of the WAS alternative promoter (1 bp shorter than the WAS alternative promoter of instant claims) into WE vector specifically mimics endogenous expression profiles in T cells (see “mimic endogenous expression profiles”; Title; see also “eGFP expression from WE vector mimics WASp endogenous expression profile” pg. 931 col. 2 and pg. 932 col. 1). Therefore, because Frecha specifically teaches the 386-bp fragment of the WAS alternative promoter results in mimicking endogenous expression profiles, this is an expected property that would arise from including the 386-bp fragment of the WAS alternative promoter as discussed above and it met by the combination of art discussed above.
Regarding claims 2-3, further to the discussion of claim 1 above, the promoter as suggested by Molina above (see claim 1 rejection above), has 100% identity to instant SEQ ID NO: 1 (the WAS promoter contained within SEQ ID NO: 4 of Molina comprises instant SEQ ID NO:1).
Regarding claims 5-6, further to the discussion of claim 1 above, Galetto teaches the expression vector is a viral vector (instant claim 5) which is a lentiviral vector (instant claim 6) (para. [0007-0012, 0029, 0035, 0071-0072, 0094, 0096, 0098-0100, 0103]; Figures 1-6; Examples 1 and 3).
Regarding claims 7-8, and 19 further to the discussion of claims 1 and 5 or 6 above, Galetto teaches the T cells, which are immune cells, as discussed above (see claims 1 and 5 rejection above) which comprise the expression construct, and Galetto teaches the T cells (Cells Expressing a 4G7-CAR; Examples 1 and 3) express at the cell surface membrane a specific chimeric antigen receptor (4G7-CAR) comprising at least one extracellular ligand binding domain (“extracellular ligand binding is a scFV derived from a CD19 monoclonal antibody, preferably 4G7” abstract; see also para. [0001, 0006, 0017-0018, 0020, 0025, 0027, 0039, 0086]; claims 1, 7 and 11) and at least one intracellular signalling domain (“at least one signal transducing domain” para. [0006] and “signal transducing domain or intracellular signaling Domain” para. [0020]; see also para. [0003, 0064]; claims 1, 3-4 and 11).
Regarding claims 9 and 20, further to the discussion of claims 1, 5 and 7 or 8 above, Galetto teaches the T cells are derived from inflammatory T-lymphocytes, cytotoxic T-lymphocytes, regulatory T- lymphocytes or helper T-lymphocytes (para. [0040]).
Regarding claims 10-11, further to the discussion of claims 1, 5 and 7 above, Galetto teaches the cells are recovered from donors (instant claim 10) or patients (instant claim 11) (“said cell can be derived from a healthy donor, from a patient diagnosed with cancer or from a patient diagnosed with an infection (para. [0040]).
Hence, the claimed invention as a whole was prima facie obvious.
Examiner’s Remark
Applicant’s amendments changed the scope of the claims and constitute a switch of inventions as discussed above and necessitated the new grounds of rejection above. For the sake of compact prosecution, arguments considered pertinent to the new grounds of rejection are addressed below.
Response to Arguments
Applicant’s arguments, filed 19th, November, 2025, have been fully considered but are not found persuasive.
Applicant argues “Applicant respectfully submits that there is no disclosure, teaching or suggestion in the cited parts of Galetta, Molina, and Frecha of "[a] T-cell that comprises an expression vector comprising a polynucleotide comprising i) a nucleotide sequence encoding a specific chimeric
antigen receptor (CAR) and ii) a promoter from the Wiskott-Aldrich syndrome locus or a fragment
thereof comprising a nucleotide sequence having at least 99% identity with the sequence as set
forth in SEQ ID NO: 1 ... and wherein an expression profile of the CAR mimics a T-cell receptor
(TCR)-like expression pattern" as recited in claim 1, as amended.” (pg. 5). Applicant argues “claim 1, as amended (from which claims 2-6 and 17-18 depend) includes elements that are not disclosed, taught, or suggested by the cited references” (pg. 9-10).
In response, the cited references, and each of their teachings as they apply to the amended claims are discussed in the new grounds of rejection under 35 U.S.C. 103 above.
Applicant argues “Galetta discloses CAR constructs using promoters to express CAR in T-cells (see, for example, Galetta, paragraphs [0028] and [0033]), but fails to disclose, teach, or suggest a promoter derived from the Wiskott-Aldrich syndrome locus or any physiological regulatory feature similar to endogenous TCR dynamics.” (pg. 9)
Applicant argues “the cited parts of Molina do not disclose, teach, or suggest a T-cell that comprises an expression vector comprising a nucleotide sequence encoding a specific chimeric antigen receptor (CAR) and ii) a promoter from the Wiskott-Aldrich syndrome locus or a fragment thereof comprising a nucleotide sequence having at least 99% identity with the sequence as set forth in SEQ ID NO: 1, and wherein an expression profile of the CAR mimics a T-cell receptor (TCR)-like expression pattern (as recited in claim 1, as amended) (pg. 9).
Applicant argues “Frecha does not disclose, teach, or suggest a T-cell comprising an expression vector encoding a CAR, wherein an expression profile of the CAR mimics a T-cell receptor (TCR)-like expression pattern ( claim 1, as amended)” (pg. 9)
In response to applicant's arguments against the references of Galetto, Molina, and Frecha 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). In the instant case, the rejection of record above is based on the combination of Galetto in view of Molina and Frecha. Galetta discloses CAR constructs using promoters to express CAR in T-cells as discussed above and Molina and Frecha teach and suggest a promoter derived from the Wiskott-Aldrich syndrome locus for the reasons stated above and as discussed above, Frecha specifically teaches the 386-bp fragment of the WAS alternative promoter results in mimicking endogenous expression profiles and therefore this is an expected property that would arise from including the 386-bp fragment of the WAS alternative promoter as discussed above and it met by the combination of art discussed above. Regarding Applicant’s argument concerning “or any physiological regulatory feature similar to endogenous TCR dynamics” this is not a requirement of instant claims. As discussed above, instant claims require “ an expression profile of the CAR mimics a T-cell receptor (TCR)-like expression pattern” which is met by the art of record for the reasons stated above. Physiological regulatory features are not recited by and therefore not required by instant claims.
Applicant argues “Frecha emphasizes sustained, high-level transgene expression for correcting genetic deficiencies (see, for example Frecha, page 934 Col. 2 paragraph 4 ("Discussion")). This concept teaches away from an expression profile of a CAR that mimics a T-cell receptor (TCR)-like expression pattern ( claim 1, as amended). Thus, Frecha teaches away from a T-cell comprising an expression vector
encoding a CAR, wherein an expression profile of the CAR mimics a T-cell receptor (TCR)-like
expression pattern, as recited in claim 1, as amended” (pg. 9-10).
In response, as discussed above, Frecha specifically teaches insertion of a 386-bp fragment of the WAS alternative promoter (99% identical to instant SEQ ID NO:2 as it is merely 1 bp shorter) into WE vector specifically mimics endogenous expression profiles in T cells (see “mimic endogenous expression profiles”; Title; see also “eGFP expression from WE vector mimics WASp endogenous expression profile” pg. 931 col. 2 and pg. 932 col. 1). Because Frecha specifically teaches the 386-bp fragment of the WAS alternative promoter results in mimicking endogenous expression profiles, Frecha does not appear to teach away from the claimed invention. Furthermore, Applicant is directed to MPEP 2145 which states that "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). See also UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 692, 2023 USPQ2d 448 (Fed. Cir. 2023) ("a reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage investigation into the invention claimed.") (internal quotations omitted) (quoting DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed. Cir. 2009)); and Schwendimann v. Neenah, Inc., 82 F.4th 1371, 1381, 2023 USPQ2d 1173 (Fed. Cir. 2023) ("Although Oez [the prior art] used a white pigment with a cross-linking polymer, it does not discourage a skilled artisan from using the white pigment without a cross-linking polymer or lead the skilled artisan in a direction divergent from the path taken in the Appealed Patents. Thus, Oez's disclosure is substantial evidence that supports the Board's finding that Oez does not teach away from the proposed combination."). In the instant case, the prior art of Frecha does not criticize, discredit or otherwise discourage investigation into the invention claimed and therefore the prior art of Frecha does not teach away from the suggested combination. Finally, as set forth previously, Frecha makes obvious combining the promoter to support supported high expression in human T cells. MPEP 2144 (IV) states that the reason or motivation to modify a reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by Applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). In instant case, the prior art teaches to use the promoter to support supported high expression in human T cells. The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Applicant argues there is no motivation to combine the cited references with a reasonable expectation of success to arrive at the claimed invention (pg. 10-12). Specifically, Applicant argues “it would not have been obvious to combine the promoter of Molina with the CAR of Galetta as motivated by Frecha to arrive at the T-cell of claim 1 comprising a promoter wherein "an expression profile of the CAR mimics a T-cell receptor (TCR)-like expression pattern". As discussed above and in the response to Non-Final Office Action dated October 16, 024, the cited parts of Molina appear silent on use of the promoter in T-cells, Galetta does not disclose a CAR construct wherein "an expression profile of the CAR mimics a T-cell receptor (TCR)-like expression pattern", and Frecha teaches away from the same” (pg. 10).
In response, the motivation to combine the references is set forth in the new grounds of rejection above. In brief, Frecha teaches a vector containing the alternative WAS promoter immediately upstream of the proximal WAS promoter supported high expression in human T cells, and is a suitable LV backbone for gene therapy of hematopoietic diseases (abstract; pg. 930) and would therefore be beneficial to the vector of Galetto, which is designed to be expressed in human T cells for gene therapy (para. [0002, 0004, 0020-0023, 0025, 0040, 0043-0045, 0051, 0059, 0064, 0083, 0085, 0091-0092, 0103]; Examples 1-3). Arguments directed to each references individually are considered above and arguments that Frecha teaches away are considered above.
Applicant argues “a promoter that comprises sequence as set forth in SEQ ID NO: 1 (claim 1, as amended) better mimics the CD3 profile (see, for example, Figure 8 of the specification as filed and reproduced below) as compared to other promoters” (pg. 10-11).
Applicant argues “the data in Figure 8 demonstrate that a T-cell comprising an expression vector comprising a nucleotide sequence encoding a specific chimeric antigen receptor (CAR) and a promoter with the sequence as set forth in SEQ ID NO: 1 (as recited in claim 1, as amended) shows CAR expression kinetics that better mimic a T-cell receptor (TCR)-like expression pattern ( claim 1, as amended), as compared to other promoters” (pg. 11-12).
In response, Applicant’s arguments are not commensurate in scope with instant claims. Specially, instant claims require the result of “an expression profile of the CAR mimics a T-cell receptor (TCR)-like expression pattern” which is an expected result for the reasons stated above. The CD3 profile or the kinetics that better mimic a T-cell receptor (TCR)-like expression pattern is not claimed and is therefore not required.
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.,” better mimics the CD3 profile” and “shows CAR expression kinetics that better mimic a T-cell receptor (TCR)-like expression pattern ( claim 1, as amended), as compared to other promoters”) 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).
Applicant argues “these results would not have been predictable to one of ordinary skill in the art in view of the cited references” (pg. 12). Applicant argues “one of ordinary skill in the art would not have a reasonable expectation of success in selecting the specific combination of elements in a manner that would allow them to arrive at a solution to the problem of obtaining an expression profile of a CAR that mimics a T-cell receptor (TCR)-like expression pattern (claim 1, as amended)” (pg. 12).
In response, Applicant’s claim is drawn to a T-cell, and therefore the reasonable expectation of success is with regard to the T-cell and its preparation. As set forth above, because Molina evidences a vector comprising the promoter and a nucleic acid of interest (Molina SEQ ID NO: 4; claim 4; pg. 6, 10), and Galetto evidences a vector comprising a polynucleotide encoding a CAR and a promoter (Figures 1-6; Example 3). Given that replacing promoter DNA sequences of a vector nucleotide for expression in a T-cell was within the skill level of one of ordinary skill in the art before the effective filing date of the claimed invention, Molina and Galetto together provide a reasonable expectation of success to substitute the promoter. Furthermore, regarding the claimed result that “an expression profile of the CAR mimics a T-cell receptor (TCR)-like expression pattern” this result appears to be an obvious result of the combination discussed above. As set forth above, Frecha specifically evidences insertion of a 386-bp fragment of the WAS alternative promoter (99% identical to instant SEQ ID NO:2 as it is merely 1 bp shorter) into WE vector specifically mimics endogenous expression profiles in T cells (see “mimic endogenous expression profiles”; Title; see also “eGFP expression from WE vector mimics WASp endogenous expression profile” pg. 931 col. 2 and pg. 932 col. 1). Therefore, because Frecha specifically teaches the 386-bp fragment of the WAS alternative promoter results in mimicking endogenous expression profiles, this is an expected property that would arise from including the 386-bp fragment of the WAS alternative promoter and one of ordinary skill would have a reasonable expectation of success in obtaining this result by using this promoter as suggested.
Applicant is additionally directed to MPEP 2143.02 which states that where there is a reason to modify or combine the prior art to achieve the claimed invention, the claims may be rejected as prima facie obvious provided there is also a reasonable expectation of success. The reasonable expectation of success requirement refers to "the likelihood of success" in combining or modifying prior art disclosures to meet the limitations of the claimed invention. See Elekta Ltd. v. ZAP Surgical Sys., Inc., 81 F.4th 1368, 1375, 2023 USPQ2d 1100 (Fed. Cir. 2023) and Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367, 119 USPQ2d 1171, 1176 (Fed. Cir. 2016). In other words, while the prior art suggests the reason for modification, it is the preparation of the modification that requires a reasonable expectation of success. Achievement of the desired result, is not necessarily required. In the instant case, one of ordinary skill would have had a reasonable expectation of success in preparing the T cell of instant claims for the reasons stated above.
Furthermore, Applicant is reminded that conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")).
Applicant argues T-cells commensurate in scope with the claims show unexpected results over the cited references (pg. 12-13). Applicant argues “As described above, Applicants have experimentally demonstrated the unexpected and advantageous CAR expression kinetics of a T-cell comprising a CAR and a promoter with the sequence as set forth in SEQ ID NO: 1 (as recited in claim 1, as amended) that better mimic a T-cell receptor (TCR)-like expression pattern as compared to other promoters (see, for example, AW ARI in Figure 8c of the present application, reproduced above, which uses a promotor of SEQ ID NO: 1). This critical advantage, which addresses safety and efficacy issues in CAR-T therapies, for example, cytokine release syndrome (CRS) and premature T-cell exhaustion (see, for example, specification as filed at page 2 lines 11-23; page 7 lines 10-12; page 23 lines 7-10; and page 23 lines 27-30), is not disclosed, taught, or suggested by the cited references, either individually or in combination” (pg. 13).
In response, as discussed above, the prior art of Frecha appears to evidence that insertion of a 386-bp fragment of the WAS alternative promoter (99% identical to instant SEQ ID NO:2 as it is merely 1 bp shorter) into WE vector specifically mimics endogenous expression profiles (see “mimic endogenous expression profiles”; Title; see also “eGFP expression from WE vector mimics WASp endogenous expression profile” pg. 931 col. 2 and pg. 932 col. 1). Therefore, because Frecha specifically teaches the 386-bp fragment of the WAS alternative promoter results in mimicking endogenous expression profiles, this appears to be an expected property that would arise from including the 386-bp fragment of the WAS alternative promoter and does not appear to be an unexpected result. Applicant is directed to MPEP 716.02 (c)(II) which states that "Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) (resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentifrice was expected based on the teaching of the prior art); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989) (Claims at issue were directed to a process of sterilizing a polyolefinic composition which contains an antioxidant with high-energy radiation. Although evidence was presented in appellant’s specification showing that particular antioxidants are effective, the Board concluded that these beneficial results would have been expected because one of the references taught a claimed antioxidant is very efficient and provides better results compared with other prior art antioxidants. (see MPEP 716.02 (c)(II)). In the instant case, because Frecha evidences mimicking endogenous expression profiles with the taught WAS alternative promoter, this appears to be an expected property that would arise from including the 386-bp fragment of the WAS alternative promoter and therefore is evidence of obviousness.
Additionally, regarding the alleged unexpected result, it is noted that the data upon which Applicant relies compares the AWARI which uses SEQ ID NO:1 with both the ARI, WARI and ARI and does not compare the data to the closest prior art. Applicant is directed to MPEP 716.02 (b) (III) which states that evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e). See In re Blondel, 499 F.2d 1311, 1317, 182 USPQ 294, 298 (CCPA 1974) and In re Fouche, 439 F.2d 1237, 1241-42, 169 USPQ 429, 433 (CCPA 1971) for examples of cases where indirect comparative testing was found sufficient to rebut a prima facie case of obviousness (MPEP 716.02 (b) (III)); see also 716.02 (e)). Applicant is additionally directed to MPEP 716.02(b) (I) and (II) which state that the evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength "are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration.") and that Applicants have the burden of explaining the proffered data. Because the evidence of the specification cited by Applicant does not directly compare the closest prior art, it is not apparent whether the evidence is statistically and practically significant.
Conclusion
No claim is allowable.
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.
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, Peter Paras can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632 /VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632