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Claims 13-16 are withdrawn.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.
Withdrawn Duplicate Claim Warning
The warning that should claim 2 be found allowable, claim 3 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof as set forth in the previous office action is withdrawn in view of Applicant’s arguments. Specifically, it is noted that Applicant argues that “whereas in claim 3, the promoter "is the sequence as set forth in SEQ ID NO: 1" (emphasis added). Thus, the promoter of claim 3 cannot include elements in addition to the sequence as set forth in SEQ ID NO: 1”(remarks filed 12th, June, 2026 pg. 5) clarifies on the record that the scope of the transitional phrase “is” is closed language.
Maintained 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 stand 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.
Response to Arguments
Applicant’s arguments, filed 12th, June, 2026, have been fully considered but are not found persuasive.
Applicant argues there is no motivation to combine the cited references with a reasonable expectation of success to arrive at the claimed invention (pg. 8-13). Applicant argues “one skilled in the art could not have combined the elements as claimed by known methods with no change in their respective functions” (pg. 8).
Specifically, Applicant argues the interpretation of “TCR-like expression profile” and Applicant argues features that “A person having ordinary skill in the art would recognize that a TCR-like expression profile refers to…” (pg. 8 last para. and pg. 8 last para. to pg. 9 last para.).
In response, this is not found persuasive because Applicant is not appreciating the broadest reasonable interpretation of instant claims. During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." (MPEP 2111).
In the instant case, Applicant’s arguments rely on the interpretation of the instantly claimed wherein clause of “wherein an expression profile of the CAR mimics a T-cell receptor (TCR)-like expression pattern.” While Applicant alleges that this claimed limitation requires specific features (pg. 8 last para. and pg. 8 last para. to pg. 9 last para.), the instant specification is silent to a specific special definition or guidance for these claimed limitations.
The claimed limitation is broader than as Applicant argues because it recites “T-cell receptor (TCR)-like expression pattern” and because it recites that is “mimics” this a “T-cell receptor (TCR)-like expression pattern.” Absent a special definition, the term “T-cell receptor (TCR)-like expression pattern” only requires that the expression pattern is “like” (similar to) a T-cell expression pattern to some degree. Furthermore, as there is no special definition or specific definition of the breadth of “mimics,” as set forth previously, 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 full breadth of the term “mimics” only requires some imitation or copying and does not require a complete or perfect copying or mimicry. Furthermore, because the data cited by Applicant is not a complete or exact copy or mimic of a T-cell expression pattern, the scope of the claimed term mimic must encompass less than exact mimicry to be consistent with the data of the specification. Finally, the claims recite “an expression profile” which is broad and can include expression distribution (such as distribution on the surface) and does not require the full kinetics or all possible features of the expression.
Applicant argues that “that the cited references do not provide one of ordinary skill in the art any motivation to arrive at the feature of "wherein an expression profile of the CAR mimics a T-cell receptor (TCR)-like expression pattern" as claimed with a reasonable expectation of success” (pg. 10-12).
In response, this is not found persuasive because as discussed above, Applicant is not appreciating the broadest reasonable interpretation of instant claims. The broadest reasonable interpretation of the claimed wherein clause is discussed above. The features relied upon by Applicant (see pgs. 8-9 and the interpretation of the wherein clause above) are not required by instant claims, which only require an expression pattern that mimics to some degree and expression pattern that is somewhat similar (i.e. “like”) a T-cell expression pattern.
Regarding motivation, as set forth above, the rejection of record provides the motivation that the promoter would be obvious to use because it supported high expression in human T cells, and is a suitable LV backbone for gene therapy of hematopoietic diseases.
Regarding the reasonable expectation of success, 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")). In the instant case, as set forth above, 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 and therefore one of ordinary skill would have a reasonable expectation of success in achieving this property by using the suggested 386-bp fragment of the WAS alternative promoter.
Applicant argues the proposed modification renders the cited art unsatisfactory for its intended purpose (pg. 13-16). Specifically, Applicant argues that because the CAR T cell of Galetto has an intended function of strong and sustained antigen-independent activation and proliferation, and Frecha teaches a fundamentally different design principle. Frecha emphasizes that gene expression must be "well-controlled” and occur "at the right levels" depending on the cell type (see, for example, Frecha,
Abstract, Introduction, and Discussion) “ (pg. 13-16). Applicant argues this creates a direct technical incompatibility with the CART cell of Galetto (pg. 13-16).
In response this is not found persuasive because Galleto generally teaches “The present invention relates to chimeric antigen receptors (CAR)” and “polynucleotides, vectors encoding said CAR and isolated cells expressing said CAR at their surface” (abstract and field of the invention). Therefore, the intended purpose of the full Galleto is to express CARs on the surface of isolated cells.
Applicant is directed to MPEP 2143 (V) which cites In re Urbanski, 809 F.3d 1237, 1244, 117 USPQ2d 1499, 1504 (Fed. Cir. 2016) (The patent claims were directed to a method of enzymatic hydrolysis of soy fiber to reduce water holding capacity, requiring reacting the soy fiber and enzyme in water for about 60-120 minutes. The claims were rejected over two prior art references, wherein the primary reference taught using a longer reaction time of 5 to 72 hours and the secondary reference taught using a reaction time of 100 to 240 minutes, preferably 120 minutes. The applicant argued that modifying the primary reference in the manner suggested by the secondary reference would forego the benefits taught by the primary reference, thereby teaching away from the combination. The court held that both prior art references "suggest[ed] that hydrolysis time may be adjusted to achieve different fiber properties. Nothing in the prior art teaches that the proposed modification would have resulted in an ‘inoperable’ process or a dietary fiber product with undesirable properties." (emphasis in original)) . In the instant case, the suggested modification does not teach away or render inoperable for its intended use because even though it would change the cells of Galetto, and therefore potentially forego the alleged the benefits taught by the primary reference (the “maximizes and sustains activation and proliferation of a CART cell” argued by Applicant; see pg. 14), nothing in the prior art teaches that the proposed modification would have resulted in an ‘inoperable’ cell that expresses a CAR, and therefore the claims are prima facie obvious and the suggested combination of art does not render the prior art of Galetto unsatisfactory for its intended purpose.
Conclusion
THIS ACTION IS MADE FINAL. 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.
No claim is allowable.
Correspondence
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/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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