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
The Examiner for this Application has changed. Please direct all future correspondence to Juliana Candelaria, AU 1634. Additional contact information can be found at the end of this paper.
This action is in response to the papers filed on 11/21/2025. Claims 149-168 are
currently pending as per claims filed on 11/21/2025. Claims 131-148 have been canceled and claims 151-168 have been newly added by Applicants’ amendment filed on 11/21/2025.
Applicant's election without traverse of Group III, claims 149 and 150 in the reply filed on 11/21/2025 is acknowledged. New claims 149-168 read on elected Group III.
Applicant’s further election without traverse of the following species is acknowledged (A) The first hinge region comprises an amino acid substitution at position 27, and the second hinge region comprises an amino acid substitution at position 44 of SEQ ID NO: 2, and
(B) The amino acid sequence of the second hinge region, as set forth in SEQ ID NO: 3.
The examiner notes that in the restricted claims of 09/25/2023 (now canceled) the examiner inadvertently included a subpart B when B should have been an alternative within species A because previously filed claims 135-141 (now canceled) limited independent claim 131 to different options of sequences for the first and second hinges.
New claims 156 to 158 (similar in scope to previously filed claims 135-138) further limit dependent claim 155 and not new independent claim 149, (as previous claims 135-138 depending on independent claim 131), whereas new claims 161-162 further limit new independent claim 149.
Therefore, claims 156-158 and 161-162 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/21/2025.
The requirement is still deemed proper and is therefore made FINAL.
Therefore, claims 149-155, 159-160 and 163-168 are subject to examination to which the following grounds of rejection are applicable.
Priority
The instant application claims is a 371 of PCT/US2021/027648 filed on 04/16/2021 which claims benefit of US Provisional patent application 63/011,494 filed on 04/17/2020.
Thus, the earliest possible priority for the instant application is 04/17/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/25/2023, 11/02/2023, 11/18/2024, and 05/27/2025 was filed after the mailing date of the current office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
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The drawings are objected to under 37 CFR 1.83(a) because they fail to show a proper legend/key for Figure 4B as captured. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 149 is objected to because of the following informalities: the abbreviations CCR and CAR should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 149-155, 159-160 and 163-168 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 applicant regards as the invention.
Claim 149 is indefinite in its recitation of “A method of reducing CCR antigen-mediated stimulation of T cell signaling in the absence of CAR antigen, compared to a CCR comprising a hinge domain without substitutions” because it is unclear how the CCR antigen-mediated stimulation of T cell signaling can be compared to a CCR comprising a hinge domain without substitutions where 1) there is not requirement that the CCR antigen-mediated stimulation of T cell signaling to require a hinge and 2) the CCR comprising a hinge domain without substitutions does not require in the absence of CAR antigen. As such the metes and bounds of the claim are in definite.
Moreover, claim 149 is incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. While all of the technical details of a method need not to be recited, the claims should include enough information to clearly and accurately describe the invention and how it is to be practice. It is unclear how expressing the CAR and a modified CCR in a cell results in reducing CCR antigen-mediated stimulation of T cell signaling in the absence of CAR antigen. The omitted steps, for example, can be a modified first hinge region of a CAR reduces CAR/CCR association in the absence of CAR antigen compared to a CAR comprising a non-modified first hinge region. It is not apparent as to under what structural or functional parameters expressing the CAR and modified CCR in a cell is indicative to the preamble of the claim (e.g. a method of reducing CCR antigen-mediated stimulation of T cell signaling in the absence of CAR antigen).
Claims 151 and 152 recite the term “and/or” in line 4. It is unclear what the metes and bounds of this term, as “and” could be interpreted to include only to reduce CCR antigen-mediated stimulation of T cell signaling in the absence of CAR antigen, or all of the claimed functions, eg., reduce CCR antigen-mediated stimulation of T cell signaling in the absence of CAR antigen and reduces CAR/CCR association in the absence of CAR antigen, or, “or” would imply that the function types are in the alternative. Appropriate correction is required.
Claim 153 recites the term “and/or” in line 2. It is unclear what the metes and bounds of this term, as “and” could be interpreted to include only the CCR hinge, or all of the hinges, or, “or” would imply that the hinge types are in the alternative. Appropriate correction is required.
Claim 154 is vague and indefinite in their recitation of the term "derived from" in that the metes and bounds of the term "derived from" are unclear. It is unclear the nature and number of steps required to obtain a "derivative" of the same or different proteins. The term implies a number of different steps that may or may not result in a change in the functional characteristics of the CAR and CCR hinge domains from the source that it is "derived from". It would be remedial to amend the claim language to use the term "obtained from", which implies a more direct method of acquiring the CAR and CCR hinge domains.
Claims 150, 159, 163-168 are also included in the rejection as they directly or indirectly depend on claim 149.
Claim Rejections - 35 USC § 112 – Scope of Enablement
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.
Claims 149-155, 159-160 and 163-168 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method of reducing CCR antigen-mediated stimulation of T cell signaling in the absence of a CAR antigen, compared to a CCR comprising a hinge domain without substitutions, the method comprising:
obtaining anti-BCMA CAR and anti-EGFR CCR polypeptides each having a CD8a hinge domain;
wherein the CAR contains a CD8a hinge domain and the CCR contains a CD8a hinge domain comprising a cysteine for a serine substitution at position 27 and 44 of SEQ ID NO: 2, and
expressing the CAR and modified CCR in a T cell;
does not reasonably provide enablement for a method comprising a genus of CAR and CCR polypeptides having a hinge domain comprising one or more cysteines substituted with a different amino acid other than serine in the CCR.
Note that the claims are examined as they read on the elected species, i.e., the first hinge region comprises an amino acid substitution at position 27, and the second hinge region comprises an amino acid substitution at position 44 of SEQ ID NO: 2
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors to be considered in determining whether undue experimentation is required are summarized in In re Wands, 858 F.2d 731, 737, 8 U.S.P.Q.2d 1400, 1404 (Fed. Cir. 1988) (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. While all of these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
the breadth of the claims; the nature of the invention:
The claims are directed to a method that comprises a vast genus of CAR and CCR polypeptides each having a hinge domain and substituting one or more cysteine residues within the CCR and/or CAR at any position with any of the 20 naturally occurring amino acids to reduce CCR antigen-mediated stimulation of T cell signaling in the absence of CAR antigen, compared to a CCR or CAR comprising a hinge domain without substitutions. The claims broadly encompass CAR and CCR polypeptides with a genus of modified hinge domains.
the amount of direction provided by the inventor; the existence of working examples:
However, the specification does not disclose a reduction to practice of a method of reducing CCR antigen-mediated stimulation of T cell signaling in the absence of CAR antigen, compared to a CCR and/or CAR comprising a hinge domain without substitutions, the method comprising substituting one or more cysteine residues within the CCR or CAR hinge domain at any position of the CCR and/or CAR hinge for another residue other than serine in the CCR. Note that claim 152 further limits claim 149 to a CAR hinge domain that has being modify at cysteine residues with any other choice of the 20 naturally occurring amino acids. Likewise, the specification does not disclose if the method can use a cell other than a T- cell. The specification describes a method that uses a CAR and CCR wherein the CAR is an anti-BCMA and the CCR is an anti-EGRF with serines in place of cysteines within the CD8alpha corresponding to positions 27 and 44 of SEQ ID NO: 2 and were transduced into T-cells (Specification: Example 4, page 114). Specification does not exemplify that any other amino acid substitution other than with serines and the substitution occurring in the hinge region of a CAR would result in the desired phenotype, nor does it exemplify these could be transduced in a cell other than a T-cell. Indeed, the polarity of a serine which contains a hydroxyl group, eliminates the ability to form disulfide bonds like cysteines, and is a unique property to serine. Therefore, the predictability of using any other amino acid is unknown and would not predict the desired phenotype.
Outside of this scope of enablement, there is no minimal or maximal physiological or phenotypic result which would necessarily tell a skilled artisan the method would give the desired result of reducing CCR-antigen-mediated stimulation of T cell signaling in the absence of CAR antigen.
the state of the prior art; the level of predictability in the art:
Sadalain et al (Cancer Discovery 2013; page 388-398, as cited in the IDS) teaches that CCRs mimic costimulatory signals, but unlike CARs, do not provide A T-cell activation signal. Their purpose is to provide costimulation in the absence of the natural costimulatory ligand on the antigen-presenting cell and they are used in conjunction with a TCR or a CAR to augment T cell reactivity (page 6, para 2). Sadalain do not teach that modifying the cysteines of the hinge domain of CCRs would permit reduced antigen-mediated stimulation of T cell signaling, let alone reduced association with a CAR via a hinge. Similarly, Kloss et al (Nat Biotechnol. 2013; page 71-76, as cited in the IDS) teaches transducing T cells with both a CAR and a CCR where each one recognizes separate antigens and using the prostate tumor antigens PSMA and PSCA,
co-transduced T cells destroy tumors that express both antigens but do not affect tumors expressing either antigen alone (abstract, page 1). Kloss teaches that dual chimeric receptor-mediated activation and costimulation of human T cells facilitates robust cytotoxicity, proliferation and tumor eradication; (page 70, legend Figure 1).Kloss also teaches methods of reducing T cell activation by changing CARs from CD19 and PSMA to PSCA and PSMA (page 72 (col 2 para 2) – page 73 (col 1 para 1) and demonstrates that three different scFvs specific for PSCA (Hzl, Mzl , Lzl) when express in T cells as CARs by linking them to CD31; cytoplasmic domains exhibit different activities in cytotoxicity assays (page 73; col. 1) supporting a model of combinatorial PSCA/PSMA targeting in prostate cancer reducing reactivity against healthy tissues expressing either antigen alone (page 74; col.2). . The author does not teach reducing the T cell activation by substituting amino residues in the hinges of the CAR and/or CCR. Finally, Ying et al (Nature Medicine 2019), teaches generating a safe CAR-T cell therapy where genetically altering sequences encoding the extracellular and intracellular domains of the CD8alpha molecule leads to reduced ability to produce cytokines (i.e. decreased T cell activation) (page 1, col 1 and 2, para 1). They found that changing the length of the amino acid sequence of the CD8alpha domain such that the intracellular and extracellular domains were longer than original polypeptide sequences resulted in reduced cytokine production (page 1, col 2, para 1). Indeed, there is no teaching of modification of the CD8alpha hinge domain such that cysteines can be substituted and length can be maintained and result in reduced stimulation of T-cell signaling.
the quantity of experimentation needed to make or use the invention based on the content of the disclosure: The skilled artisan would be required to perform under levels of experimentation in order to practice the claimed invention. The instant specification does not reduce to practice the claimed invention; the instant specification does not provide guidance on how to reasonably predict which a genus of CCR or CAR polypeptides, other than anti-EGFR and anti-BCMA, respectively, and what amino acid substitution at any location of a hinge, other than a CCR CD8a hinge domain comprising a cysteine to a serine at position 27 and 44 of SEQ ID NO: 2 that would permit the desired result of reducing antigen-mediated stimulation of T cell signaling. Thus, the skilled artisan would be forced to 1) which CCR and CAR to use and its combination of which cysteines to substitute at any position with which amino acids and which type of cell to transduce with the resulting polypeptide/vector, and 2) generate the cell harboring modified CAR and/or CCR and determine if the modification was sufficient to reduce CCR antigen-mediated stimulation of T cell signaling by running various experiments to demonstrate reduced cytokine levels.
the level of one of ordinary skill:
The level of one of ordinary skill is a PhD holder.
Conclusion
When all of the Wands factors are considered together, they establish a prima facie case that the specification is not enabling for the claims. While a lack of a working embodiment cannot be a sole factor in determining enablement, the lack of any working examples, in light of the unpredictable nature of the art and the lack of direction applicants present, provides additional weight to the lack of enablement in consideration of the Wands factors as a whole. Thus, one of ordinary skill in the art would not have had a reasonable expectation of success in making or using the claimed invention.
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.
Claim(s) 149-155, 159, 160, 163-168 are rejected under 35 U.S.C. 103 as being unpatentable over Chaudhary et al (WO 2020/02844; as cited in the IDS), further in view of Van de Stegen et al (Nature Reviews, 2015; page 499-509; as cited in IDS), Schönfeld et al (US Patent No. 9212229), and Wu et al (US Patent No. 12227589).
Regarding claim 149, Chaudhary teaches costimulatory receptors comprising, but not limited to, a receptor containing extracellular ligand binding domain of DcRl, DcR2, DR4, DRS, CD27, CD28, 41BB, OX40, GITR and BCMA fused via a transmembrane domain to the cytosolic domain of a costimulatory receptor ([ ‘the extracellular ligand binding domain ofDcRl, DcR2, DR4, DRS, CD27, CD28, 41BB, OX40, GITR and BCMA fused via a transmembrane domain to the cytosolic domain of a costimulatory receptor”: para 0044, page 19). Moreover, Chaudhary teaches the CAR-T cells express a CAR targeting CD19 and co-express CD27 (para 0044, page 20) and CAR components containing a hinge domain (Table 7a - hCDS-Hinge-TM). Chaudhary also teaches a hinge domain on a CD28 construct (the CCR) (Table 7a - CD28-Hinge-TM-cytosolic-domain). Additionally, van der Stegen teaches a CD28-based CCR (page 2, para 4) and fusion of the CCR to a CD3zeta chain-based CAR (page 2, para 4) with a hinge (Figure 1C).
However, Chaudhary and van der Stegen do not teach substituting one or more cysteine residues within the CCR hinge domain for another residue, thereby producing a modified CCR.
However, Schönfeld teaches chimeric antigen receptors characterized by an optimized hinge region (linker region) (col 3, page 9, line 40), the linker region (iii) is a modified hinge region of the human CD8 alpha-chain, wherein the human CD8 alpha-chain hinge region is modified by replacing the cysteine residue(s) with (a) serine residue(s) or deleting the cysteine residue(s) (col 2, page, 8, line 49) and a host cell expressing the multi-functional protein or comprising the nucleic acid or the expression construct (col 2, page, 8, line 64). Cysteine modifications taught in Schönfeld permits more efficient surface expression and high functionality in lymphocytes (page 8, col 2, line 31-34).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of Chaudhary and van der Stegen comprising a fusion protein that expresses a CAR and CCR polypeptides each having a hinge domain with the teachings of Schönfeld on substituting out the cysteines in the hinge domain of the CCR or/and CAR, in order to enhance the activity profile of a fusion construct comprising two or more hinge regions, particularly because Schönfeld teaches that cysteine modifications allow more efficient surface expression and high functionality in lymphocytes.
In relation to the recitation of “A method of reducing CCR antigen-mediated stimulation of T cell signaling in the absence of CAR antigen” in the preamble of claim 149, the structure of the cell exemplified by the combined teachings of Chaudhary, van der Stegen, and Schönfeld is the same as the cell in claim 1. Therefore, the properties of the cell would be reasonably expected to be the same. Thus, one of ordinary skill in the art would be motivated to combine the teachings of Chaudhary, van der Stegen, and Schönfeld to arrive at the claimed limitations of claim 149 in order to reduce CCR antigen-mediated stimulation of T-cell signaling in the absence of a CAR antigen with a reasonable expectation of success.
Regarding claim 150, the combined teachings of Chaudhary, van der Stegen, and Schönfeld render obvious claim 149. Moreover, Schönfeld teaches a CAR and “the linker region (iii) is a modified hinge region of the human CD8 alpha-chain, wherein the human CD8 alpha-chain hinge region is modified by replacing the cysteine residue(s) with (a) serine residue(s)” (col 2, page, 8, line 49), rendering obvious wherein the CAR hinge domain comprises one or more cysteines substituted with a different amino acid.
Regarding claim 151, the combined teachings of Chaudhary, van der Stegen, and Schönfeld render obvious claim 149. Moreover, claim 151 limits claims 149 to one or more cysteine substitutions within the CCR hinge domain. As previously set above, the combined teachings of Chaudhary, van der Stegen, and Schönfeld render obvious the structure of claim 1. Therefore, the properties of the cell would be reasonably expected to be the same. Thus claim 151 is directed to an inherent result based on the methodology of using the structure of the same claimed cell. Furthermore, in the instant case the “wherein” clause of the cell provides no patentable weight, as the characteristics (“wherein the one or more cysteine substitutions within the CCR hinge domain (i) reduces CCR antigen-mediated stimulation of T cell signaling in the absence of CAR antigen, compared to a CCR comprising a hinge domain without cysteine substitutions”) are a direct result of the structure of the cell of the independent claim, absent evidence to the contrary. The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) and In re Tomlinson, 363 F.2d 928, 150 USPQ 623 (CCPA 1966). See M.P.E.P. § 2112.02.
Regarding claim 152, the combined teachings of Chaudhary, van der Stegen, and Schönfeld render obvious claim 149. Moreover, claim 152 limits claim 149 to one or more cysteine substitutions within the CAR hinge domain. As previously set above, the combined teachings of Chaudhary, van der Stegen, and Schönfeld render obvious the structure of claim 1. Moreover, Schönfeld teaches a CAR and “the linker region (iii) is a modified hinge region of the human CD8 alpha-chain, wherein the human CD8 alpha-chain hinge region is modified by replacing the cysteine residue(s) with (a) serine residue(s)” (col 2, page, 8, line 49). Therefore, the properties of the cell would be reasonably expected to be the same. Thus, claim 152 is directed to an inherent result based on the methodology of the structure of the same claimed cell. Thus, in the instant case the “wherein” clause of the cell provides no patentable weight, as the characteristics (“reduces CCR antigen-mediated stimulation of T cell signaling in the absence of CAR antigen compared to a CAR comprising a hinge domain without cysteine substitutions”) are a direct result of the structure of the cell of the independent claim, absent evidence to the contrary.
Regarding claim 153, the combined teachings of Chaudhary, van der Stegen, and Schönfeld render obvious claim 149. Moreover, Schönfeld teaches a CAR and “the linker region (iii) is a modified hinge region of the human CD8 alpha-chain, wherein the human CD8 alpha-chain hinge region is modified by replacing the cysteine residue(s) with (a) serine residue(s)” (col 2, page, 8, line 49), rendering obvious wherein the one or more cysteine residues within the CCR and/or CAR hinge domains are substituted with serine(s) or alanine(s).
Regarding claim 154, the combined teachings of Chaudhary, van der Stegen, and Schönfeld render obvious claim 149. Moreover, van der Stegen teaches that CD3, CD4, or CD25 can be used for CAR design and CD28 can be used for CCR construct design (page 2, Principles of T cell activation and CAR design, para 2 and 3), rendering obvious the CAR and CCR hinge domains are derived from the same or different proteins.
Regarding claim 155, the combined teachings of Chaudhary, van der Stegen, and Schönfeld render obvious claim 149. Moreover, Schönfeld teaches a CAR and “the linker region (iii) is a modified hinge region of the human CD8 alpha-chain, wherein the human CD8 alpha-chain hinge region is modified by replacing the cysteine residue(s) with (a) serine residue(s)” (col 2, page, 8, line 49), rendering obvious wherein the CAR and CCR hinge domains are CD8a hinge domains or a functional fragment thereof.
Regarding claim 159, the combined teachings of Schönfeld, Kloss, and Ying render obvious claims 149 and 155. The combined teachings do not disclose the specific positions wherein the CCR CD8a hinge domain comprises amino acid substitutions at positions 27 and 44 of SEQ ID NO: 2.
However, Wu teaches a CAR with a CD8 hinge domain comprising an amino acid substitution at the equivalent positions of cysteine residues 27 and 44 (Page 20, col 7, line 34; SEQ ID NO: 19) having 95.6% similarity to SEQ ID NO: 2 of instant application claim 159, rendering obvious these two positions for substituting one or more cysteine residues within the CAR and CCR CD8a hinge domains (see alignment below).
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Regarding claim 160, the combined teachings of Chaudhary, van der Stegen, and Schönfeld render obvious claim 149. Moreover, Chaudhary teaches a CAR with a hinge region comprising an amino acid sequence domain of SEQ ID NO: 18918with 100% identity to SEQ ID No: 3 in the instant application (see alignment below).
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Regarding claims 163-166 and 168, the combined teachings of Chaudhary, van der Stegen, and Schönfeld render obvious claim 149. Moreover Chaudhary discloses introducing into effector cells nucleic acids encoding the claimed fusion peptides where CAR-T cells express, for example, CD19 and CD70, Her2 and co-express 41BB and other fusion proteins (para [0039], [0043]-[0044], [0049],[00119],[00154]).
Regarding claim 167, the combined teachings of Chaudhary, van der Stegen, and Schönfeld render obvious claims 149 and 166. Moreover, Chaudhary discloses transfecting immune effector cells; e.g., T cells, NK cells (para. [00568]) and, Schönfeld teaches wherein the host cell is selected from effector cells of the immune system, and wherein the effector cells of the immune system are natural killer (NK) cells, natural killer T (NKT) cells, or a lymphocyte preparation containing NK cells and NKT cells (claim 6), rendering obvious the method of claim 166, wherein the cell is (i) an immune effector cell, (ii) a T-cell, (iii) a CD3+, CD4+, and/or CD8+ cell, (iv) a cytotoxic T lymphocytes (CTLs), a tumor infiltrating lymphocytes (TILs), or a helper T cell, (v) a natural killer (NK) or natural killer T (NKT) cell, or (vi) a macrophage.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliana Candelaria whose telephone number is (571)272-5488. The examiner can normally be reached Monday - Friday 8am - 5pm.
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/JULIANA IRENE CANDELARIA/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634