DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim(s) 24-34 are pending.
Preliminary Amendments
Applicant’s preliminary amendment filed on 12/14/2023 and 02/07/2024 are acknowledged. The abstract was amended to remove legal phraseology. The claims were amended remove multiple dependencies and transform “use” to a methods claim. The specification was amended to add in the cross-reference to priority applications and sequence listing statements.
It is of note: Both preliminary amendments filed recite the same date of submission “December 14, 2023” despite one being filed on 12/14/2023 and the other on 02/07/2024. In both submissions, there is a repeat of abstract, claim, and specification amendments stated verbatim (see above), however, on 02/07/2024, an 82-page specification was submitted without a “cleaned” or “marked up” header, and without notice of a substitute specification in the remarks. This 82-page specification did not incorporate the amendments to the specification filed on 12/14/2023, i.e., the cross-reference to priority applications and sequence listing statements. The specification amendment was to fix the shading that was in Table 1 on page 50. Thus, the “substitute specification” provided on 02/07/2024 has not been entered.
Applicant’s preliminary amendment filed on 07/02/2026 is acknowledged. The claims were amended to (1) cancel claims 1-22, (2) amend claims 23 and 24, and (3) add claims 25-34.
Election/Restrictions
Applicant’s election without traverse of Group II in the reply filed on 07/02/2026 is acknowledged.
Applicant’s election without traverse of Species of (a) SEQ ID NO: 1 as one sequence of Tim 3; (b) SEQ ID NO: 11 as one additional inhibitory receptor; (c) SEQ ID NO: 24 as one sequence from one TCR chain; and (d) Cancer as the disease from claim 24, in the reply filed on 07/02/2026 is acknowledged.
In the reply filed on 07/02/2026, Applicant added claim(s) 25-34. Claim(s) 29-32 are drawn to a nonelected species. Thus, claim(s) 29-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/02/2026.
Claim(s) 23-28 and 33-34 are under consideration.
Priority
Acknowledgement is made that this application is a 371 of PCT/EP2022/053040 filed 02/08/2022 and claims priority based on foreign application filed as EP21155865.5 on 02/08/2021.
All claims are given the priority date of 02/08/2021.
Information Disclosure Statement
Receipt of the information disclosure statement(s) on 08/03/2023 is acknowledged. The signed and initialed PTO-1449 form(s) has/have been mailed with this action.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Page 50 of the specification, i.e., table 1, does not have corresponding SEQ ID NOs: with each of the specifically defined nucleotide sequences.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
Substitute Specification
The substitute specification filed 02/07/2024 has not been entered because it does not conform to 37 CFR 1.125(b) and (c) because: (1) the specification submitted on 02/07/2024 does not include the specification amendments filed on 12/14/2023.
Trademark(s) and/or Tradenames
The use of the term(s), which is a trade name or a mark used in commerce, has been noted in this application.
Incucyte (p.60, line 21);
Nucleofector (p.54, line 34);
Prism (p.59, line 15);
FlowJo (p.59, line 5)
BD FACSCANTO (p.59, line 4);
BD FACSYMPHONY (p.59, line 4)
BD LSRFORTESSA (p.59, line 4)
FIX & PERM (p.58, line 27)
LegendPlex (p.57, line 27 and 31)
(10) Bioanalyzer (p. 56, line 6)
(11) ddPCR (p. 56, line 12)
(12) AutoDG (p.56, line 15)
(13) Quantasoft (p. 56, lines 21 and 22)
(14) QIAamp (p. 55, lines 8)
(15) Geneart (p. 54, line 5)
(16) TrypLE (p.51, line 22)
The term(s) should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Embedded Hyperlink
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Page 78, line 29;
Page 79, line 4;
Page 79, line 16;
Page 81, line 26;
Page 52, line 11;
Page 52, line 14.
Minor informalities
The disclosure is objected to because of the following informalities:
Page 43, line 20, the I in NIH is a 1, it would be remedial to amend this to recite “NCBI/NIH”.
Table 1 on page 50 contains shading. It would be remedial to remove said shading.
Appropriate correction is required.
Claim Objections
Claim 23 objected to because of the following informalities:
There is a comma instead of a period after “23”;
“Cas” at the end of line 9 should be “Cas9”;
IR should be spelled out when first introducing it since IR (inhibitor receptor) is an abbreviation and not a gene symbol; and
It would be remedial to amend the “SEQ ID No:” to “SEQ ID NO:” for consistency between claims, e.g., claim 28 recites “SEQ ID NO:”.
Claim 26 is objected to because of the following informalities:
It would be remedial to amend the “SEQ ID No:” to “SEQ ID NO:” for consistency between claims, e.g., claim 28 recites “SEQ ID NO:”.
Claim 27 is objected to because of the following informalities:
There is an extra space between “of” and “SEQ ID No:11”.
It would be remedial to amend the “SEQ ID No:” to “SEQ ID NO:” for consistency between claims, e.g., claim 28 recites “SEQ ID NO:”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) - indefiniteness
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.
Claim(s) 24, 25, 28, and 33 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 24 recites the limitation ". . . administering a composition of claim 23 to a patient in need thereof.", in the last two lines. There is insufficient antecedent basis for this limitation in the claim. Claim 23 is a methods claim. There are many compositions within claim 23, e.g., the guide RNAs, the CRISPR/Cas9 system, and the isolated cell. Thus, it is unclear which composition claim 24 is referencing back to.
This rejection can be overcome by amending claim 24 to recite, “. . . administering an isolated cell comprising: one or more guide RNA (gRNA) or nucleic acid sequence encoding the gRNA, wherein the gRNA is selected from the group consisting of:
(A) a gRNA comprising the guide sequence of SEQ ID NO: 1;
(B) a further gRNA comprising the guide sequence of SEQ ID NO: 11; and
(C) a gRNA comprising the guide sequence of SEQ ID NO: 1, and a further gRNA comprising the guide sequence of SEQ ID NO: 11; and
Cas9 or a nucleic acid sequence encoding Cas9 in a CRISPR/Cas 9 system of claim 23 to a patient in need thereof.”
Claim 25 recites the limitation ". . . the composition further comprises . . ." in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 23 is a methods claim. There are many compositions within claim 23, e.g., the guide RNAs, the CRISPR/Cas9 system, and the isolated cell. Thus, it is unclear which composition claim 25 is referencing back to.
Claim 26 recites the limitation ". . . the guide sequence is SEQ ID No: 1 . . ." in line 1.
There is insufficient antecedent basis for this limitation in the claim. Claim 23 recites “. . . (A) a gRNA comprising a guide sequence selected from SEQ ID Nos: 1-10; or (B) a further gRNA comprising a guide sequence selected from SEQ ID Nos: 11-23 and 25-27; or . . .”. Claim 23 uses “a guide sequence”, recited twice, to further describe either “a gRNA” or “a further gRNA”.
This rejection can be overcome by amending claim 26 to recite “. . . wherein the gRNA comprises the guide sequence of SEQ ID NO: 1.”, (similar language to claim 27).
Claim 28 recites the limitation "the further gRNA comprises the guide sequence of SEQ ID NO: 24". There is insufficient antecedent basis for this limitation in the claim. Claim 23 recites, “a further gRNA comprising a guide sequence selected from SEQ ID Nos: 11-23 and 25-27.” Thus, there is no antecedent basis for SEQ ID NO: 24.
This rejection can be overcome by amending claim 23 to include SEQ ID NO: 24.
Accordingly, claim 33 is rejected for being dependent upon claim 24.
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.
Claim(s) 23-28 and 33-34 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.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, Applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
Claim(s) 23-28 and 33-34 is drawn to a genus of “(A) a gRNA comprising a guide sequence selected from SEQ ID Nos: 1-10”, “(B) a further gRNA comprising a guide sequence selected from SEQ ID Nos: 11-23 and 25-27”, “(C) a combination of the gRNA according to A and the gRNA according to B”, or “(D) a nucleic acid molecule encoding said gRNA” for altering the expression of an IR gene and optionally of TRAC and/or TRBC1/2 in an isolated cell. The rejected claims thus belong to the broad class of any sequence of 2 or more nucleotides from SEQ ID NOs: 1 and/or 11 (i.e., the elected species) or a nucleic acid molecule encoding 2 or more nucleotides from said gRNA and as having the function of altering the expression of an IR gene and optionally of TRAC and/or TRBC1/2 in an isolated cell.
Claim 26 limits claim 23 to wherein the guide sequence is SEQ ID No: 1. Accordingly, claim 26 is drawn to a species of SEQ ID NO:1, i.e., at the full length of SEQ ID NO: 1, an must function as altering the expression of an IR gene and optionally of TRAC and/or TRBC1/2 in an isolated cell either individually or in combination with any sequence of 2 or more nucleotides from “(B) a further gRNA comprising a guide sequence selected from SEQ ID Nos: 11-23 and 25-27”.
Claim 27 limits claim 23 to wherein the further gRNA comprises the guide sequence of SEQ ID No: 11. Accordingly, claim 27 is drawn to a species of gRNA comprising the sequence of SEQ ID NO:11, i.e., at minimum the full length of SEQ ID NO: 11, and that must function as altering the expression of an IR gene and optionally of TRAC and/or TRBC1/2 in an isolated cell either individually or in combination with any sequence of 2 or more nucleotides from “(A) a gRNA comprising a guide sequence selected from SEQ ID Nos: 1-10”.
To satisfy the written description requirement, MPEP §2163 states, in part “… a patent
specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.” Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species 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 functional and structure, or by a combination of such
identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.”
The specification envisions the “(A) a gRNA comprising a guide sequence selected from SEQ ID Nos: 1-10”, “(B) a further gRNA comprising a guide sequence selected from SEQ ID Nos: 11-23 and 25-27”, “(C) a combination of the gRNA according to A and the gRNA according to B”, or “(D) a nucleic acid molecule encoding said gRNA” as the following:
“The terms "polynucleotide", "nucleotide", "nucleotide sequence", "nucleic acid" and
"oligonucleotide" are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. . . In aspects of the presently disclosed subject matter the terms "chimeric RNA", "chimeric guide RNA", "guide RNA", "single guide RNA" and "synthetic guide RNA" are used interchangeably and refer to the polynucleotide sequence comprising the guide sequence. The term "guide sequence" refers to the about 20 bp sequence within the guide RNA that specifies the target site and may be used interchangeably with the terms "guide" or "spacer".”, (p. 38, 8-15).
“In general, a guide sequence is any polynucleotide sequence having sufficient complementarity with a target polynucleotide sequence to hybridize with the target sequence and direct sequence specific binding of a CRISPR complex to the target sequence. . . In some embodiments, a guide sequence is about or more than about 5, 10, 11, 12, 13, 14, 1 5, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50, 75, or more nucleotides in length. In some embodiments, a guide sequence is less than about 75, 50, 45, 40, 35, 30, 25, 20, 15, 12, or fewer nucleotides in length.”, (p. 40, lines 20-22 and 30-34).
Table 1 describes gRNA sequences targeting TIM-3, LAG-3, 2B4, TRAC, TRBC1/2, CD39, and PD-1.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims in regard to structure and function, the examples are only representative of the sequences enumated in Table 1 used for altering the expression of an IR gene and optionally of TRAC and/or TRBC1/2 in an isolated cell. These results are not necessarily predictive of all “any sequence of 2 or more nucleotides from SEQ ID NOs: 1 and/or 11 (i.e., the elected species) or a nucleic acid molecule encoding 2 or more nucleotides from said gRNA” capable of altering the expression of an IR gene and optionally of TRAC and/or TRBC1/2 in an isolated cell. Thus, it is impossible for one to extrapolate from the table 1 “any sequence of 2 or more nucleotides from SEQ ID NOs: 1 and/or 11 (i.e., the elected species) or a nucleic acid molecule encoding 2 or more nucleotides from said gRNA” described herein that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of “any sequence of 2 or more nucleotides from SEQ ID NOs: 1 and/or 11 (i.e., the elected species) or a nucleic acid molecule encoding 2 or more nucleotides from said gRNA” capable of altering the expression of an IR gene and optionally of TRAC and/or TRBC1/2 in an isolated cell.
Looking to a review article on sequence length of guide RNAs, Fu et al (Improving CRISPR-Cas nuclease specificity using truncated guide RNAs, nature biotechnology, vol 32, pages 279-284, published January 26th, 2014) describes “any sequence of 2 or more nucleotides from SEQ ID NOs: 1 and/or 11 (i.e., the elected species) or a nucleic acid molecule encoding 2 or more nucleotides from said gRNA” structure and function:
Fu et al teaches, “We also found that tru gRNAs containing a mismatched 5′ G and 17 nucleotides of complementarity could efficiently direct Cas9-induced indels, whereas those bearing a mismatched 5′ G and 16 nucleotides of complementarity showed lower or undetectable activities compared with matched full length gRNAs (Supplementary Fig. 3), consistent with our results that a minimum of 17 nucleotides of complementarity is required for efficient RGN activity.”, (p. 280, col 2, para 1).
Fu et al teaches in Figure 1b, guide RNAs with 15 nucleotides did not elicit any activity, and in Figure 1c, guide RNAs with 16 nucleotides did not elicit any significant activity (p.280).
Therefore, the art does not appear to offset the deficiencies of the specification. Merely describing “(A) a gRNA comprising a guide sequence selected from SEQ ID Nos: 1-10”, “(B) a further gRNA comprising a guide sequence selected from SEQ ID Nos: 11-23 and 25-27”, “(C) a combination of the gRNA according to A and the gRNA according to B”, or “(D) a nucleic acid molecule encoding said gRNA” reading on “any sequence of 2 or more nucleotides from SEQ ID NOs: 1 and/or 11 (i.e., the elected species) or a nucleic acid molecule encoding 2 or more nucleotides from said gRNA” capable of altering the expression of an IR gene and optionally of TRAC and/or TRBC1/2 in an isolated cell without sufficient detail relating to the genus and its function does not allow the skilled artesian to reasonably conclude that the Applicants were in possession of the claimed invention in claim(s) 23-28 and 33-34.
One way to overcome this rejection is to amend claim 23 to recite, “An in vitro or ex vivo method of altering expression of an inhibitor receptor (IR) gene and optionally of TRAC and/or TRBC1/2 gene, in an isolated cell, said method comprising introducing into the isolated cell one or more guide RNA (gRNA) or nucleic acid sequence encoding the gRNA, wherein the gRNA is selected from the group consisting of:
(A) a gRNA comprising the guide sequence of SEQ ID NO: 1;
(B) a further gRNA comprising the guide sequence of SEQ ID NO: 11; and
(C) a gRNA comprising the guide sequence of SEQ ID NO: 1, and a further gRNA comprising the guide sequence of SEQ ID NO: 11; and
Cas9 or a nucleic acid sequence encoding Cas9 in a CRISPR/Cas9 system, wherein the guide RNA targets the gene and the Cas9 protein cleaves the genomic loci of the DNA molecules encoding the one or more gene products, whereby expression of the one or more gene products is decreased or abolished.”
Claim Rejections - 35 USC § 112(d) – Improper dependent
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim(s) 24 and 33 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 24 is drawn to an in vitro or in vivo method for the treatment of a condition selected from the group consisting of: cancer. . . the method comprising administering a composition of claim 23 to a patient in need thereof. Claim 24 is an improper dependent claim because it requires only a product recited within claim 23 and does not include all of the limitations of claim 23.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Accordingly, claim 33 is rejected for being dependent upon claim 24.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 23-28 and 33-34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al (US 2018/0362975 A1, published December 20th, 2018).
Of note: CRISPR/Cas9 system is being interpreted as “a. a Cas9 protein or a nucleic acid molecule encoding a Cas9 protein, and b. at least one gRNA or at least one nucleic acid molecule as herein defined, wherein the system and/or a. or b. are comprised in a ribonucleoprotein complex (p. 11, lines 30-34 to p.12 lines 1-2).
Regarding claim(s) 23 and 25-28, Chen et al discloses, “[T]he present disclosure relates to gRNA molecules, CRISPR systems, cells, and methods useful for genome editing of cells, e.g., T cells, e.g., T-cells further engineered to express a chimeric antigen receptor, and useful for treating diseases such as cancers.” (para [0004]).
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At para [0034], Chen et al discloses wherein the gRNA molecule of HAVCR2, also known as TIM3, is SEQ ID NO: 3464, which is 100% identical to instant SEQ ID NO: 1 (see alignment below)
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At para [0035], Chen et al discloses wherein the gRNA molecule of LAG3 is SEQ ID NO: 3791, which is 100% identical to instant SEQ ID NO: 11 (see alignment below).
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At para [0008], Chen et al discloses wherein the gRNA molecule of TRAC is SEQ ID NO: 5572, which is 100% identical to instant SEQ ID NO: 24 (see alignment below).
Chen et al discloses, “The following general aspects of the gRNA molecule may be combined, alone or in combination, with any of the gRNAs comprising a targeting domain described herein, for example, a targeting domain recited in any of the aforementioned aspects and embodiments.”, (para [0041]).
Lastly, Chen et al discloses, “In embodiments of the gRNA molecule, including in any of the aforementioned aspects and embodiments, when a CRISPR system (e.g., an RNP as described herein, e.g., an RNP that includes a Cas9 molecule, for example as described herein) including the gRNA molecule (e.g., as described herein) is introduced into a cell (or population of cells) as described herein, expression of the gene including the target sequence complementary to the targeting domain of the gRNA molecule is reduced or eliminated in said cell.”, (para [0091]).
Regarding claim(s) 24 and 33, Chen et al discloses, “In another aspect, the invention provides a method of treating a subject having a disease associated with expression of a tumor antigen, e.g., a proliferative disease, a precancerous condition, a cancer, and a non-cancer related indication associated with expression of the tumor antigen, the method including administering to the subject an effective amount of a cell as described herein, for example, a cell of any of the aforementioned cell aspects and embodiments. In embodiments, the disease associated with expression of a tumor antigen is cancer or a non-cancer related indication. . . In embodiments, the cancer is a hematologic cancer selected from the group consisting of chronic lymphocytic leukemia (CLL), acute leukemias, acute lymphoid leukemia (ALL), B-cell acute lymphoid leukemia (B-ALL), T-cell acute lymphoid leukemia (T-ALL), chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), B cell prolymphocytic leukemia, blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, diffuse large B cell lymphoma, follicular lymphoma, hairy cell leukemia, small cell- or a large cell-follicular lymphoma, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, marginal zone lymphoma, multiple myeloma, myelodysplasia and myelodysplastic syndrome, non-Hodgkin's lymphoma, Hodgkin's lymphoma, plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, Waldenstrom macroglobulinemia, and pre-leukemia.”, (para [0239]).
Regarding claim 34, which is a product-by-process claim, Chen et al teaches, “In embodiments of the gRNA molecule, including in any of the aforementioned aspects and embodiments, when a CRISPR system (e.g., an RNP as described herein, e.g., an RNP that includes a Cas9 molecule, for example as described herein) including the gRNA molecule (e.g., as described herein) is introduced into a cell (or population of cells) as described herein, expression of the gene including the target sequence complementary to the targeting domain of the gRNA molecule is reduced or eliminated in said cell.”, (para [0091]).”
Chen et al teaches gRNA targeting an IR, i.e., Tim-3 and Lag-3 at paragraphs [0034] and [0035] (see sequence alignment above).
Accordingly, claim(s) 24-28 and 33-34 are anticipated by Chen et al.
Conclusion
No claims allowed.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571) 272-2916. 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.
/L.M.T./Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
Prosecution Insights