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 .
Election/Restrictions
Applicant’s election without traverse of SEQ ID NO: 56 and SEQ ID NO: 54 was previously acknowledged.
In the reply filed 10/15/25, Applicants amended claims 1 and 15. Claims 7-11 were cancelled.
Claims 1-6 and 12-24 are pending and under consideration.
Drawings
The drawings were received on 10/15/25. These drawings are acceptable.
Claim Rejections-Withdrawn
The rejection of claims 8-9 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 due to cancelation of the claims.
The rejection of claims 1, 12-14 and 17-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated over Ma et al. (WO2017/112877, cited on IDS) is withdrawn due to amendment of claim 1.
The rejection of claims 1-4, 6, 12-13 and 17-24 rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (WO2017/112877,published 6/29/2017 cited on IDS) in view of Studnicka et al. (USPN 5,869,619,cited on IDS) is withdrawn due to amendment of claim 1.
The rejection of claims 1-7, 12-13 and 17-24 rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (WO2017/112877,published 6/29/2017 cited on IDS), Studnicka et al. (USPN 5,869,619) in view of Foster et al. (US2016/0046700,cited on IDS) and Whitlow et al. (“An improved linker for single-chain Fv with reduced aggregation and enhanced proteolytic stability” Protein Eng. 1193, Nov; 6(8):989-95,cited on IDS) is withdrawn due to amendment of claim 1.
The rejection of claims 1, 10-14 and 17-24 rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (WO2017/112877, cited on IDS) in view of GenBank AAX36174.1 (July 26,2016) is withdrawn due to amendment of claim 1.
The rejection of claims 1, 10-24 under 35 U.S.C. 103 as being unpatentable over Ma et al. (WO2017/112877, cited on IDS) in view of JarJour et al. (USPN 10,428,142) is withdrawn due to amendment of claim 1.
Claim Rejections - 35 USC § 112-Maintained
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
The rejection of claims 1-6 and 12-24 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention is maintained.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Scope of the claimed genus
Claim 1 is drawn to a polynucleotide encoding a CAR comprising a CD5 specific scFv comprising a VL and VH and IL-15,(i) wherein the CD5 specific scFv comprises an scFV portion of the sequence set forth in SEQ ID NO: 30 or an amino acid sequence having at least 85% sequence identity to the scFv portion of the sequence set forth in SEQ ID NO: 30 or (ii) wherein the scFv comprises the CDRs of the scFv set forth in SEQ ID NO:30, wherein for (i) or (ii), the IL-15 comprises the amino acid sequence set forth in SEQ ID NO: 56 or an amino acid sequence having at least 85% sequence identity thereto. Claims 2 is drawn to wherein the VL comprises and amino acid sequence of SEQ ID NO: 31 or a sequence having at least 90% sequence identity to framework regions of SEQ ID NO: 31. Claim 3 is drawn to wherein the VH comprises and amino acid sequence of SEQ ID NO: 32 or a sequence having at least 90% sequence identity to framework regions of SEQ ID NO: 32. Claim 5 is drawn to wherein the scFv comprises the sequence set forth in SEQ ID NO: 30 or an amino acid sequence having at least 90% sequence identity thereto. Claim 15 is drawn to the CD3 zeta domain comprises the amino acid sequence set forth in SEQ ID NO: 54 or an amino acid sequence having at least 90% sequence identity thereto.
The USPTO provides claim terms with broadest reasonable interpretation in light of the specification. The instant specification defines “chimeric antigen receptors (CARs)” as artificial T cell receptors, chimeric T cell receptors or chimeric immunoreceptors… and comprise a intracellular activation domain, a transmembrane domain, an extracellular domain comprising a tumor associated antigen binding region….. In certain cases, CARS comprise domains for additional co-stimulatory signaling such as CD3zeta….” [PGPUB 0082].
Assessment of whether species are support in the original specification
Four embodiment of the invention of the claims. The specification reduces to practice the CD5Ev3-CAR and hCD5Ev3-CAR. The specification further reduces to practice a CAR comprises DAP12 endodomain, such as CD5Ev3DAP12-CAR or hCD5Ev3CAP12-CAR. The “h” is for humanized.
There was no disclosure of other CARs comprising CD5 specific scFv comprising a VL and VH. With respect to IL-15, the specification discloses SEQ ID NO: 56. respect CD3zeta, the specification discloses SEQ ID NO: 54. The specification does not disclose sequences having at least 90% sequence identity thereto. Furthermore, the specification does not adequately describe the amino acids that constitute the “scFv” portion, the CDRs or the framework regions. The specification does not define the boundaries (i.e. amino acid residues) that make up these specific regions.
In summary, for these reasons, the skilled artisan would reasonably conclude that the inventor(s), at the time the application was filed, had possession of CD5Ev3-CAR, hCD5Ev3-CAR, CD5Ev3DAP12-CAR and hCD5Ev3CAP12-CAR at the time the invention was filed.
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, the disclosure of the CD5Ev3-CAR, hCD5Ev3-CAR, CD5Ev3DAP12-CAR and hCD5Ev3CAP12-CAR are not representative of the genus because the genus encompassed by the claims is large. Claim 1 does not limit the CAR to any specific intracellular activation domain, transmembrane domain, an extracellular domain comprising a tumor associated antigen binding region, endodomain or co-stimulatory molecule. Importantly, if one considers that variants (at least 85% identity) and “portions” of the CAR components are also contemplated, the genus is enormous.
Therefore, disclosure of CD5Ev3-CAR, hCD5Ev3-CAR, CD5Ev3DAP12-CAR and hCD5Ev3CAP12-CAR are not representative of the genus.
Identifying characteristics and structure/function correlation
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe the structural, physical and/or chemical properties of the polynucleotides that lead to the claimed function of CD5 specific CAR.
This is an issue of written description. The specification does not make clear which proteins are in the genus and which are not because it does not describe the physical basis for the claimed activity. In other words, the specification does not describe which polynucleotides to make.
In conclusion, for the reasons presented above, the skilled artisan would reasonably conclude that the inventors, at the time the application was filed had full possession of CD5Ev3-CAR, hCD5Ev3-CAR, CD5Ev3DAP12-CAR and hCD5Ev3CAP12-CAR.
Response to Arguments
Applicant's arguments filed 10/15/25 have been fully considered but they are not persuasive. Applicants argue that claim 1 was amended to recite specific CD5 scFV portions. Applicants argue that a skilled artisan would understand applicants had possession of the invention at the time of filing.
This argument is not persuasive because the disclosure of the CD5Ev3-CAR, hCD5Ev3-CAR, CD5Ev3DAP12-CAR and hCD5Ev3CAP12-CAR are not representative of the genus because the genus encompassed by the claims is large. Claim 1 does not limit the CAR to any specific intracellular activation domain, transmembrane domain, an extracellular domain comprising a tumor associated antigen binding region, endodomain or co-stimulatory molecule. Importantly, if one considers that variants (at least 85% identity) and “portions” of the CAR components are also contemplated, the genus is enormous.
For the reasons presented above, the rejection is maintained.
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 1-6 and 12-24 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.
An scFv is an antibody fragment that comprises a VL and VH and their respective framework regions and CDRs. Please note that instant SEQ ID NO: 30 comprises SEQ ID NO: 31 and 32. SEQ ID NO: 30 comprises from the N to C-terminus: Signal peptide-SEQ ID NO: 31-linker sequence-SEQ ID NO: 32. Therefore, SEQ ID NO: 31 and 32 comprise an scFV portion (VL or VH). SEQ ID NO: 31 comprises the VL and SEQ ID NO: 32 comprises the VH sequence.
Claims 1 is indefinite because it is unclear what residues comprise scFv portion of SEQ ID NO: 30 or the CDRs of SEQ ID NO: 30. The specific portions or boundaries of the specific regions of the sequence is not defined in the claim or the specification and one of ordinary skill in the art would not be able to determine the metes and bounds of the claim.
Claims 2-4 are indefinite because it is unclear what residues comprise the framework region of SEQ ID NO: 31 and 32. The boundaries of the framework regions are not defined in the claim or the specification and one of ordinary skill in the art would not be able to determine the metes and bounds of the claim.
Claims 5-6 and 12-24 are rejected for depending from rejected claims 1-4.
Claim Rejections - 35 USC § 103-NEW
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.
Claims 1-4, 6, 12-14 and 17-24 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (WO2017/112877, cited on IDS) in view of Studnicka et al. (USPN 5,869,619,cited on IDS) and GenBank AAX36174.1 (July 26,2016). This is a new rejection necessitated by amendment of the claims
With respect to claim 1 (a), Ma et al. teach chimeric antigen receptors (CARs) (Abstract). Ma et al. teach generation of CD5CAR (Fig. 1A-1D). Ma et al. teach the CD5CAR comprises anti-CD5 scFv (Fig. 1A). Fig. 1B discloses the CD5CAR comprises a variable heavy and light chain. Ma et al. claims and teaches polynucleotide sequence encoding the CARs (claim 28; p. 25, lines 10-11, p. 30, lines 8-9).
With respect to claim 1 (b), Ma et al. teach and claim an embodiment providing a CD5CAR engineered cell that co-expressed a transgene and releases a transgenic product, such as IL-15. (claim 16 and bottom of p. 46).
Ma et al. does not teach the sequence CD5 specific scFV portion is SEQ ID NO: 30 or an amino acid sequence at least 85% sequence identity to SEQ ID NO: 30 the VL and VH sequence (claims 2-5). However, the teachings of Studnicka et al. cure this deficiency.
An scFv is an antibody fragment that comprises a VL and VH and their respective framework regions and CDRs. Please note that instant SEQ ID NO: 30 comprises SEQ ID NO: 31 and 32. SEQ ID NO: 30 comprises from the N to C-terminus: Signal peptide-SEQ ID NO: 31-linker sequence-SEQ ID NO: 32. Therefore, SEQ ID NO: 31 and 32 comprise an scFV portion (VL or VH). SEQ ID NO: 31 comprises the VL and SEQ ID NO: 32 comprises the VH sequence. Please note that the claim 1 does not require 85% sequence identity to entirety of SEQ ID NO: 30, the claim requires an scFv portion of SEQ ID NO: 30 or an amino acid sequence at least 85% sequence identity to the scFv portion of SEQ ID NO: 30 or the CDRs or SEQ ID NO: 30.
Studnicka et al. claim a protein comprising a light chain variable region (SEQ ID NO: 87) and a heavy chain variable region (SEQ ID NO: 88) (claim 9). SEQ ID NO: 87 of Studnicka et al. is 96.3% identical to SEQ ID NO: 31. SEQ ID NO: 88 is 89.7% identical to instantly claimed SEQ ID NO: 32. Studnicka et al. also teach SEQ ID NO: 27 and 29 that are identical to instantly claims SEQ ID NO: 31 and 32 respectively. Please see sequences below. Therefore, SEQ ID NO: 87, 88, 27 and 29 meet the limitation of (i) and (ii) and claims 2-4.
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Studnicka et al. teach the anti-CD5 antibodies were found to be particularly useful in several therapeutic regimens (col. 6, 4th para.).
It would have been obvious to a person of ordinary skill in the art to optimize the sequence of the CAR comprising a CD5 specific scFv comprising the VL and VH of Studnicka et al. because the sequences are known in the art and Studnicka et al. teach the are capable of binding antigen when combined. In particular, a person of ordinary skill in the art would have a motivation to the use the VL and VH of Studnicka et al. because the reference teaches they were particularly useful in several treatment regimens. There is a reasonable expectation of success given the sequences are known VL and VH sequences.
Ma et al. does not teach the sequence of IL-15 is SEQ ID NO: 56 or an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 56. However, the teaching of GenBank cure this deficiency.
GenBank teaches the sequence of IL-15 is AAX36174.1, which is identical to instantly claimed SEQ ID NO: 56.
It would have been obvious to a person of ordinary skill in the art to use the GenBank sequence of the IL-15 of Ma et al. because it is the sequence of IL-15. There is a reasonable expectation of success given that the Ma et al. teach the use of IL-15 and GenBank teaches the sequence of IL-15. Furthermore, the sequence of IL-15 is well known in the art.
With respect to claim 6, Studnicka et al. teach that studies provide an example of one therapeutic target (CD5) for the development of methods for the humanization of murine anti-Tcell antibodies (col. 6, 4th para.). Studnicka et al. teach the non-human (i.e. murine) variable region residues may be modified to contain amino acid residues of human origin (col. 6, 6th para.).
With respect to claims 12 and 13, Fig. 1A discloses the CD5CAR comprises CD28. Ma et al. teach the CD5CARs contain costimulatory domains (p. 44, lines 17). Ma et al. teach that in some embodiments CD5CAR includes at least one of transmembrane domains from CD28 (p. 44, lines 22-23). CD28 is a costimulatory molecule that comprises an extracellular domain, transmembrane domain and intracellular signaling domain.
With respect to claim 14, Fig. 1A discloses the CD5CAR comprises CD3zeta. Ma et al. teach the CD5CARs include CD3 zeta (p. 44, line14).
With respect to claim 17, Fig 1A discloses the CD5CAR comprises a CD5 specific scFv, a CD28 domain and a CD3 zeta domain.
With respect to claims 18 and 19, Ma et al. teach in a preferred embodiment, the CAR polypeptide is part of an expressing gene or cassette and includes an accessory gene or tag in addition to the CD5CAR. The accessory gene maybe an inducible suicide gene, such as caspase 9 gene (p. 34, 1st para.; p. 45, lines 22-23).
With respect to claims 20-24, Ma et al. teach CD5CAR expression in NK-92 cells (p. 75, lines 9-11). NK-92 cell are natural killer cells, meeting the limitations of “immune cell”, “NK cell” and “host cell”.
Claims 1-6, 12-14 and 17-24 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (WO2017/112877,published 6/29/2017 cited on IDS), Studnicka et al. (USPN 5,869,619) and GenBank AAX36174.1 (July 26,2016) in view of Foster et al. (US2016/0046700,cited on IDS) and Whitlow et al. (“An improved linker for single-chain Fv with reduced aggregation and enhanced proteolytic stability” Protein Eng. 1193, Nov; 6(8):989-95,cited on IDS). This is a new rejection necessitated by amendment of the claims
The teachings of Ma et al. and Studnicka et al. and GenBank are presented in detail above.
Studnicka et al. teach the sequences of SEQ ID NO: 31 and 32, but do not teach the entire sequence of SEQ ID NO: 30 that comprises a signal peptide (at the N-terminus) and linker sequence (between SEQ ID NO: 31 and 32). However, the teachings of Foster et al and Whitlow et al. cure this deficiency.
Foster et al. teach CARs (chimeric antigen receptors) [0006]. Foster et al. teach that chimeric proteins can contain a signal sequence at the N-terminus [0241]
Foster et al. teach the signal peptide of SEQ ID NO: 165 (MEFGLSWLFLVAILKGVQCSR) [0748].
Whitlow et al. teach a linker sequence GSTSGSGKPGSGEGSTKG for scFv that had reduced aggregation and was found to be more stable to proteolysis (abstract). Whitlow et al. teach the linker linked the VL and VH sequences (Table 1).
With respect to claim 5, It would have been obvious to a person of ordinary skill in the art to use the signal peptide of Foster et al. and linker sequence of Whitlow et al. in order create an scFv that meets the limitations of SEQ ID NO: 30. A person of ordinary skill in the art would have a motivation to include the signal peptide in order to target the sequence and the linker in order to improve the properties of the scFv. There is a reasonable expectation of success given that all components of the scFv are well known in the art and the method of making the proteins are routine in the art.
Claims 1-4, 6 and 12-24 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (WO2017/112877, cited on IDS), Studnicka et al. (USPN 5,869,619,cited on IDS), GenBank AAX36174.1 (July 26,2016) in view of JarJour et al. (USPN 10,428,142). This is a new rejection necessitated by amendment of the claims
The teachings of Ma et al., Studnicka et al. and GenBank are presented above. The references teach the CAR comprises a CD3zeta domain, however the reference does not teach the CD3zeta sequence is SEQ ID NO: 54. However, the teachings of JarJour et al. cure this deficiency.
With respect to claims 15-16, JarJour et al. teach chimeric antigen receptors comprising a CD3 zeta domain (col. 2, lines 38-40, Fig. 15A, col. 4, lines 1-2). JarJour et al. teach SEQ ID NO: 15, which comprises the CD3zeta sequence:
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The CD3zeta sequence of JarJour et al. is 98.8% identical to instantly claimed SEQ ID NO: 54. The JarJour et al. sequence is missing the C-terminal amino acid
(a proline). MPEP 2144.05 states obviousness of similar and overlapping ranges, amounts and proportions. In particular, MPEP 2144.05 states: a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v.Banner, 778 F.2d 775, 783,227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of “having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium” as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. “The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties.”). In the instant case, JarJour et al. teach a CAR comprising an CD3zeta domain that is 98.8% identical to instantly claimed SEQ ID NO: 54, which is close to the 100% to SEQ ID NO: 54. There is a reasonable expectation of success given the great similarity between sequences having 98.8% and 100% identity to SEQ ID NO: 54, one of ordinary skill in the art would reasonably conclude that the sequences have similar properties.
Response to Arguments
Applicant's arguments filed 10/15/25 have been fully considered but they are not persuasive. Applicants argue that Ma et al. does not teach amended claim 1.The Examiner agrees that Ma et al. no longer anticipates the claims. However, claim 1 is obvious in view Studnicka et al. and GenBank.
Conclusion
No claims are allowed.
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/TARA L MARTINEZ/Examiner, Art Unit 1654