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 05/05/2026 are acknowledged.
Claims 54, 56-61, and 63-74 are pending.
Claims 1-53, 55, and 62 are canceled.
Claims 54, 56-61, and 63-73 are amended.
Claim 74 is new.
Claims 66-67 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/06/2025.
Therefore, claims 54, 56-61, 63-65, and 68-74 are under examination.
Withdrawn
The remarks regarding the sequence disclosure are withdrawn. Applicant has submitted a substitute specification with corrected sequence identifiers.
The objections to the drawings are withdrawn. Applicant has submitted replacement drawings to overcome the objections.
The objections of claims 57-59, 69, and 70 are withdrawn. Applicant has amended the claims to overcome the objections.
The previous rejections of claims 54-65 and 68-73 under 35 U.S.C. 112(b) are withdrawn. Applicant has amended the claims to overcome the rejections. However, new rejections under 35 U.S.C. 112(b) are applied below.
The rejection of claim 62 under 35 U.S.C. 112(d) is withdrawn. Applicant has canceled the claim to overcome the rejection.
The rejections of claims 54, 56-58, 60-64, and 68-73 under 35 U.S.C. 112(a) written description, as it was applied to previous claim limitations that encompassed variable CDR sequences, are withdrawn. Applicant has amended claim 54 to overcome this 112(a) rejection.
The rejection of claim 72 under 35 U.S.C. 112(a) enablement is withdrawn. Applicant has amended the claim to overcome the rejection.
The double patenting rejections of claims 54 and 68-72 over copending Application No. 18/261,149 are withdrawn. Applicant has amended claim 54 to overcome the rejections.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/05/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 59 objected to because of the following informalities: Claim 59 recites “(ii) the VH-CDRs 1, 2, and 3 comprises the amino acid sequences 30, 36 and 8”. For correct grammar, the “comprises” should read as “comprise”. Appropriate correction is required.
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 64, 68, 70, and 72-73 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.
Claim 64 recites the limitation “an analog thereof having 85% sequence identity” in regards to the TM domain and costimulatory domain together, the activation domain, and the leading sequence. It is unclear if the 85% sequence identity is to the listed sequences for the TM domain and costimulatory domain together, the activation domain, and the leading sequence, respectively, (i.e. SEQ ID NO: 17, 16, and 19) or if this is referring to another sequence because there is no sequence identifier succeeding “having 85% sequence identity”.
Claim 68 recites the limitation “a cell comprising the CAR according to claim 54 or a nucleic acid molecule encoding the CAR or a construct or a vector comprising the nucleic acid molecule.” There are three embodiments in this claim that can stand on their own. The first is “a cell comprising the CAR according to claim 54”, the second is “a nucleic acid molecule encoding the CAR” and the third is “a construct or a vector comprising the nucleic acid molecule”. The second and third embodiments do not depend from a specific claim so, it is unclear if these encompass the CAR of claim 54 or not. If these embodiments are meant to depend from claim 54, they lack antecedent basis because there is no mention of a “nucleic acid molecule”, “construct”, or “vector” in claim 54. Additionally, if the second embodiment is meant to depend from claim 54, the claim limitation of “a nucleic acid molecule encoding the CAR” is already encompassed by withdrawn claim 66.
Claim 70 recites the limitation “T cells comprising the CAR according to claim 54 or a nucleic acid encoding the CAR”. There are two embodiments in this claim that can stand on their own. The first is “T cells comprising the CAR according to claim 54” and the second is “a nucleic acid encoding the CAR”. The second embodiment does not depend from a specific claim so, it is unclear if this encompasses the CAR of claim 54 of not. If this embodiment is meant to depend from claim 54, it lacks antecedent basis because there is no mention of “a nucleic acid encoding the CAR”. Additionally, if the second embodiment is meant to depend from claim 54, the claim limitation of “a nucleic acid encoding the CAR” is already encompassed by withdrawn claim 66.
Claim 72 recites the limitation “a therapeutically effective amount of cells according to claim 68 or a pharmaceutical composition comprising the cells”. There are two embodiments in this claim that can stand on their own. The first is “a therapeutically effective amount of cells according to claim 68”. The second is “a pharmaceutical composition comprising the cells”. The second embodiment does not depend from a specific claim so, it is unclear if this encompasses the cell according to claim 68 or not. If this is meant to depend from claim 68, it lacks antecedent basis because there is no mention of “the cells”. Additionally, if the second embodiment is meant to depend from claim 68, the claim limitation of “a pharmaceutical composition comprising a plurality of cells according to claim 68 and a pharmaceutically acceptable carrier” is already encompassed by claim 71.
Claim 73, which depends from claim 72, is therefore rejected for the same reasons as above.
Maintained Rejections
Claim Rejections - 35 USC § 112(a)
Written Description
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.
This rejection has been modified solely to address the amendments to claims 63 and 64.
Claims 63 and 64 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. 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 63 is drawn to the CAR, wherein the CAR is characterized by at least one of: (i) the TM domain is a TM domain of a receptor selected from CD28 and CD8, or an analog thereof; (ii) the costimulatory domain is selected from a costimulatory domain of a protein selected from CD28, 4-1BB, OX40, iCOS, CD27, CD80, CD70, an analog thereof, and any combination thereof; (iii) the TM domain and the costimulatory domain are both derived from CD28; (iv) wherein the antigen binding domain is linked to the TM domain via a spacer; (v) wherein the activation domain is selected from FcRy and CD3-zeta activation domains; and (vi) further comprising a leading peptide. Claim 64 is drawn to the CAR of claim 63, wherein the CAR is characterized by at least one of: (i) the TM domain and the costimulatory domain together have the amino acid sequence SEQ ID NO: 17 or an analog thereof having at least 85% sequence identity; (ii) the spacer comprises the amino acid sequence comprising from 1 to 4 repetitions of amino acid sequence SEQ ID NO: 16; (iii) the activation domain is FcRy having amino acid sequence SEQ ID NO: 18 or an analog thereof having at least 85% sequence identity; and (vi) the leading peptide has amino acid sequence SEQ ID NO: 19 or an analog thereof having at least 85% sequence identity.
The specification teaches SEQ ID NO: 17 for the TM domain and/or the costimulatory domain for CD28 [see paragraphs 73 and 183], SEQ ID NO: 18 for the FcyR ITAM intracellular signaling domain [see paragraph 183], and SEQ ID NO: 19 for the signaling peptide [see paragraphs 82 and 183]. The specification further teaches that “analog” refers to a polypeptide, peptide or protein which differs by one or more amino acid alterations (e.g., substitutions, additions or deletions of amino acid
residues) from the original sequence, having at least 70% sequence identity to the original sequence and still maintains the properties of the parent polypeptide, peptide or protein. The specification provides no examples of “analogs” of SEQ ID NOs: 17, 18, or 19, of analogs for CD28 and CD8 for the TM domain, or of analogs for CD28, 4-1BB, OX40, iCOS, CD27, CD80, and CD70 for the costimulatory domain. The specification further does not provide any guidance on which residues could be modified while still maintaining the function of the recited proteins, nor does the specification teach any functional “analog” of the recited proteins.
One means of providing adequate written description and evidence of
possession of a claimed genus is through providing sufficient distinguishing identifying
characteristics of the genus. The factors to be considered include disclosure of
complete or partial structure, physical and/or chemical properties, functional
characteristics, structure/function correlation, methods of making the claimed product,
or any combination thereof. In this case, the claim does not require that the modifications be made at specific amino acid residues or in a particular region of the sequences, and thus, the claims are drawn to a broad genus of “analogs” for the recited proteins.
Claims 63 and 64 are drawn to variable sequences for TM domain, costimulatory domain, the activation domain, and the leading peptide without any requirement for where modifications can occur within the parent sequences. Making deletions, insertions, or substitutions to a polypeptide sequence, while requiring the polypeptide to still maintain its function, is highly unpredictable. Bhattacharya et al., 2017 (02/05/2026 PTO-892) teaches that the range of possible effects of even single variations at the protein level are significantly greater than currently assumed by existing software prediction methods, and that correct prediction of consequences remains a significant challenge [page 18, third paragraph]. Fenton et al., 2020 (02/05/2026 PTO-892) teaches that while it is well known that most substitutions at conserved amino acid positions (which they call “toggle” switches) abolish function, it is also true that substitutions at nonconserved positions (which they call “rheostat” positions) are equally capable of affecting protein function, and that each substitution has a different functional outcome, and the set of substitutions spans a range of outcomes [see Abstract]. Further, Guo et al., 2004 (02/05/2026 PTO-892) teaches that the effects of mutations on protein function are largely additive [page 9207, left column, third paragraph], supporting that when multiple mutations are introduced, there is even less predictability. Thus, it is clear that the structure of variable sequences of proteins does not predictably correlate with the function thereof.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must
describe an invention and does so in sufficient detail that one skilled in the art can
clearly conclude that "the inventor invented the claimed invention." Lockwood v.
American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re
Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he
description must clearly allow persons of ordinary skill in the art to recognize that [the
inventor] invented what is claimed."). Thus, an applicant complies with the written
description requirement "by describing the invention, with all its claimed limitations, not
that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention."
Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
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. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if
the disclosure "indicates that the patentee has invented species sufficient to constitute
the gen[us]. "See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v.
Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir.
2004) "[A] patentee of a biotechnological invention cannot necessarily claim a genus
after only describing a limited number of species because there may be unpredictability
in the results obtained from species other than those specifically enumerated."). "A
patentee will not be deemed to have invented species sufficient to constitute the genus
by virtue of having disclosed a single species when ... the evidence indicates ordinary
artisans could not predict the operability in the invention of any species other than the
one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir.
2004).
Thus, based on the lack of teachings in the specification and the teachings in the art, Applicant has failed to meet the written description of “analogs” of SEQ ID NOs: 17, 18, or 19, of analogs for CD28 and CD8 for the TM domain, or of analogs for CD28, 4-1BB, OX40, iCOS, CD27, CD80, and CD70 for the costimulatory domain. Therefore, one of skill in the art would not conclude that Applicant was in possession of the instantly claimed invention.
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.
Claims 54, 56-61, 63, and 68-74 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-37 and 45 of Application No. 17/779,720 (‘720; reference application; now U.S. Patent No. 12,552,874) in view of Chmielewski et al., 2013 (02/05/2026 PTO-892).
Regarding claims 54, 56-60, and 74 of the instant application, claim 30 of ‘720 teaches a monoclonal antibody (mAb) or a fragment thereof that specifically binds to Sialyl Lewis A glycan (SLeA), wherein the mAb or the fragment comprises an antigen binding domain comprising a heavy-chain variable domain (VH) and a light-chain variable domain (VL) each comprising three complementarity determining regions (CDRs) wherein the VH-CDR 1, 2 and 3 comprise amino acid sequences SEQ ID NOs: 15, 12, and 8, respectively, and the VL-CDRs 1, 2 and 3 comprise amino acid sequences SEQ ID NOs: 9, 10 and 11, claim 31 of ‘710 teaches the mAb or fragment according to claim 30, wherein VHCDR1 comprises amino acid sequence selected from SEQ ID NO: 6 and 15, and the VH-CDR2 comprises amino acid sequence selected from SEQ ID NO: 12 and 21, claim 32 of ‘720 teaches the mAb or fragment according to claim 30, wherein the CDRs 1, 2, and 3 of the VH domain comprises amino acid sequences SEQ ID NOs: 15, 21 and 8, respectively, the CDRs 1, 2, and 3 of the VL domain comprise amino acid sequences SEQ ID NOs: 9, 10 and 11, respectively, a VH-framework domains (FRs) 1, 2, and 4 amino acid sequences SEQ ID NOs: 24, 26 and 27, respectively, and a VL-FR1 comprising the amino acid sequence SEQ ID NO: 28, and claim 33 of ‘720 teaches the mAb or fragment according to claim 30, comprising: i. a set of six CDR sequences comprising SEQ ID NOs: 15, 21, 8, 9, 10 and 11; ii. a set of four VH framework sequences comprising SEQ ID NOs: 24, 26, 29 and 27; and iii. a set of four VL framework sequences comprising SEQ ID NOs: 28, 30, 31 and 32, claim 34 of ‘720 teaches the mAb or the fragment according claim 30, wherein the VH domain comprises amino acid sequence set forth in SEQ ID NO: 3 and the VL domain comprises amino acid sequence set forth in SEQ ID NO: 5, claim 35 of ‘720 teaches the mAb or the fragment according to claim 30, wherein the fragment is a single chain variable fragment (scFv), and claim 36 of ‘720 teaches the mAb or the fragment according to claim 35, wherein the scFv comprises an1ino acid sequences SEQ ID NO: 3 and SEQ ID NO: 5.
SEQ ID NOs: 15, 21, and 8 of ‘720 have 100% sequence identity to SEQ ID NOs: 15, 21, and 8 of the instant claims, respectively, and SEQ ID NOs: 9, 10, and 11 of ‘720 have 100% sequence identity to SEQ ID NOs: 9, 10, and 11 of the instant claims, respectively. SEQ ID NO: 3 of ‘720 has 95.9% sequence identity to SEQ ID NO: 1 of the instant claim and SEQ ID NO: 5 of ‘720 has 98.9% sequence identity to SEQ ID NO: 4 of the instant claim. Regarding claims 60 and 74, SEQ ID NOs: 3 and 5 of ‘720 have 100% sequence identity to SEQ ID NOs: 3 and 5, respectively, of the instant claims. Additionally, regarding claims 57 and 58, SEQ ID NO: 3 has non-conservative substitutions at positions 1, 110, 114 relative to SEQ ID NO: 1.
However, ‘720 does not specifically teach a chimeric antigen receptor (CAR) comprising the mAb (i.e. antigen binding domain).
Chmielewski teaches that antibody-based CAR T cells enables the targeting of antigens of different compositions and structure such as peptides, carbohydrates, or inorganic compounds [page 2, left column, second paragraph] and further teaches CARs comprising antibodies that target T cells toward carbohydrate antigens like CA19-9 (i.e. SLeA) [page 2, right column, third paragraph].
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 CAR that targets CA19-9 (SLeA) of Chmielewski to comprise the mAb (antigen-binding domain) of ‘720 that binds SLeA. One would have been motivated to make this modification because It is prima facie obvious to substitute equivalents known for the same purpose (see MPEP 2144.06 (II)). Further, one would have been motivated to use these sequences for the antigen binding domain that binds to SLeA because they are known sequences, and it is obvious to use known variations for predictable outcomes. See MPEP 2143 (F).
Regarding claim 61, claim 37 of ‘720 teaches the mAb or fragment according to claim 36, wherein the scFv comprises amino acid sequence SEQ ID NO: 22 or an analog thereof having at least 90% sequence identity to said sequence.
SEQ ID NO: 22 of ‘720 has 100% sequence identity to SEQ ID NO: 15 of the instant claim.
Regarding claim 63, Chmielewski teaches that the CD3 gamma chain initiates the downstream signaling for T-cell activation (i.e. activation domain) [see page 2, Figure 1].
Regarding claim 68-70, Chmielewski teaches CAR modified T cells [page 1, right column, third paragraph and page 3, right column, see “The CAR Strategy” section].
Regarding claim 71, claim 45 of ‘720 teaches a pharmaceutical composition comprising the mAb or the fragment according to claim 30 or a conjugate thereof, and a pharmaceutically acceptable carrier.
Regarding claims 72 and 73, ‘720 teaches a method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the antibodies [0029] and also teaches the method comprises administering a pharmaceutical composition comprising cells or expressing the mAb to the subject [0119]. ‘720 further teaches that the cancer is lung or pancreatic adenocarcinomas, colon carcinoma, HER2-neg breast carcinoma, or pharynx squamous cell carcinoma [0028 and 0113]. See the decisions in Sun Pharmaceuticals v Eli Lily Fed Cir July 28, 2010; Geneva v GlaxoSmithKline 349, F.3d 1373; and Pfizer v Teva 518 F3d 1353 supporting the Office's use of disclosed utilities of compositions when applying double patenting rejections to method claims.
Claims 54, 56-61, 63-64, and 68-74 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-37 and 45 of Application No. 17/779,720 (‘720; reference application; now U.S. Patent No. 12,552,874) in view of Chmielewski et al., 2013 (02/05/2026 PTO-892), as applied to claims 54, 56-61, 63, and 68-74 above, and further in view of Perera (WO2018057585; 02/05/2026 PTO-892).
The teachings of ‘720 and Chmielewski are above.
However, ‘720 and Chmielewski do not specifically teach that the leading peptide has the amino acid sequence of SEQ ID NO: 19, as set forth in option (vi) of instant claim 64.
Regarding claim 64, Perera teaches the use of a signal (leading) peptide (i.e. N-terminal to the antigen binding domain) in the structure of a CAR which facilitates expression of the CAR on the surface of the cell and can be the mouse immunoglobulin light chain kappa signal sequence consisting of SEQ ID NO: 4 [page 32, lines 27-33 – page 33, lines 1-3].
SEQ ID NO: 4 of Perera has 100% sequence identity to SEQ ID NO: 19 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 CAR, as taught by ‘720 and Chmielewski, to comprise the signal peptide of Perera. One would have been motivated to have made this modification because Perera teaches that the signal peptide facilitates expression of the CAR on the cell surface, and further, one would have been motivated to have used the sequence of Perera for the signal peptide sequence because it is a known sequence in the art, and it is obvious to use known variations in the prior art for predictable outcomes. See MPEP 2143 (F).
Claims 54, 56-61, 63-65, and 68-74 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-37 and 45 of Application No. 17/779,720 (‘720; reference application; now U.S. Patent No. 12,552,874) in view of Chmielewski et al., 2013 (02/05/2026 PTO-892) and Perera (WO2018057585; 02/05/2026 PTO-892), as applied to claims 54, 56-61, 63-64, and 68-74 above, and further in view of Zhang (WO 2018200586; 02/05/2026 PTO-892), Bublik (WO 2019030757; 02/05/2026 PTO-892), and Chen et al., 2013 (02/05/2026 PTO-892).
The teachings of ‘720, Chmielewski, and Perera are above.
However, ‘720, Chmielewski, and Perera do not specifically teach that the CAR comprises the amino acid sequence of SEQ ID NO: 20.
Regarding claim 65, SEQ ID NO: 20 of instant claim 65 comprises multiple sequences for different components as shown below:
- Residues 1-22 of SEQ ID NO: 20 correspond to SEQ ID NO: 19 for the leading peptide.
- Residues 23-259 of SEQ ID NO: 20 correspond to SEQ ID NO: 15 for the scFv.
- Residues 260-269 correspond to 2 repeats of SEQ ID NO: 16 for the spacer.
- Residues 270-379 correspond to SEQ ID NO: 17 for the TM domain and the costimulatory domain.
- Residues 380-417 correspond to SEQ ID NO: 18 for the FcRy activation domain.
To reiterate the teachings, Perera teaches the use of a signal (leading) peptide of SEQ ID NO: 4 which has 100% sequence identity to SEQ ID NO: 19 of the instant claim. ‘720 teaches the scFv of SEQ ID NO: 22 which has 100% sequence identity to SEQ ID NO: 15.
Zhang teaches a CD28 transmembrane/intracellular signaling domain fusion protein that can be used in the construction of a CAR comprising SEQ ID NO: 530 [see paragraph 0418].
SEQ ID NO: 530 of Zhang has 100% sequence identity to SEQ ID NO: 17 of the instant application.
Bublik teaches SEQ ID NO: 10, a human Fc gamma receptor, for the activation domain of a CAR [0011]. Bublik further teaches a CAR comprising a leader peptide, an antigen binding domain, a TM domain of CD28, a costimulatory domain of CD28, and an activation domain of FcRy [0011]. Bublik also teaches that there is a spacer between the antigen binding domain and the transmembrane domain [0045].
SEQ ID NO: 10 of Bublik has 100% sequence identity to SEQ ID NO: 18 of the instant application.
Chen teaches a linker of GGGGS(2) which is a flexible linker (spacer) for the use in fusion proteins (i.e. a CAR) that improves biological activity [see page 1360, Table 3].
The individual sequences when put together create a sequence with 100% sequence identity to SEQ ID NO: 20 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 combined the individual sequences, as taught by the respective art, to arrive at SEQ ID NO: 20 of the instant claim. One would have been motivated to combine these specific components to arrive at the claimed CAR because they are known components in the art for creating a functional CAR. Further, one would have been motivated to use these sequences for each of the components that form SEQ ID NO: 20 because they are known sequences in the art, and it is obvious to use variations known in the art for predictable outcomes. See MPEP 2143 (F).
Response to Arguments
The rejections of claims 63 and 64 under 35 U.S.C. 112(a) written description are maintained. On page 12 of the remarks, Applicant argues that they are of the opinion that the field of CARs is well established and a person skilled in the art would clearly know which domains from which receptors may be used and combined when creating the transmembrane and intracellular part of the CAR, that the provided sequences are merely examples of known domains which are widely used in CAR methodology, and therefore, Applicant believes that combining the demonstrated sequences together with a common knowledge claims 63 and 64 are well supported, that these claims define parts of the CAR that are well known and commonly used, and there is no reason to restrict these claims to specific sequences. This is not found persuasive because Applicant provides no objective evidence supporting that a person skilled in
the art would clearly know which domains from which receptors may be used and combined when creating the transmembrane and intracellular part of the CAR, specifically “analogs” as encompassed by the claims. Applicant is reminded that “arguments of counsel cannot take place of factually supported objective evidence” (see MPEP §2145). Claims 63 and 64 recite the limitation “an analog thereof” and claim 64 recites the limitation of “at least 85% sequence identity”, and as set forth in the rejection, the specification teaches that “analog” refers to a polypeptide, peptide or protein which differs by one or more amino acid alterations (e.g., substitutions, additions or deletions of amino acid residues) from the original sequence, having at least 70% sequence identity to the original sequence and still maintains the properties of the parent polypeptide, peptide or protein. The specification provides no examples of “analogs” of SEQ ID NOs: 17, 18, or 19, of analogs for CD28 and CD8 for the TM domain, or of analogs for CD28, 4-1BB, OX40, iCOS, CD27, CD80, and CD70 for the costimulatory domain. The specification further does not provide any guidance on which residues could be modified while still maintaining the function of the recited proteins, nor does the specification teach any functional “analog” of the recited proteins. Therefore, there is no expectation that a person skilled in the art would know what “analog” may be used in the invention as claimed. Thus, these claims lack written description and the rejection is maintained. See above.
The double patenting rejections over Application No. 17/779,720 (now U.S. Patent No. 12,552,874) are maintained. On page 14 of the remarks, Applicant requests that the rejection be held in abeyance. A request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an OBJECTION or REQUIREMENTS AS TO FORM (see 37 CFR 1.111(b) and MPEP §714.02). Thus, the double patenting rejections of record have been maintained as no response to these rejections has been filled by applicant at this time.
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.
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.
/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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