Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group I (claims 196-213) in the reply filed on December 16, 2025 is acknowledged. The traversal is on the ground(s) that there is not a serious burden to search each invention This is not found persuasive because the search for the nucleic acid encoding is different from a search for a polypeptide. Both the nucleic acid and polypeptide searches would be different, and have different classifications as well.
The requirement is still deemed proper and is therefore made FINAL.
Claims 214-215 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on December 16, 2025.
Claims 196-213 are under examination.
Information Disclosure Statement
The Information Disclosure Statements filed August 29, 2022 and March 27, 2024 have been considered.
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 - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
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 incorporation-by-reference paragraph, 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.
The Sequence Listing Incorporation by Reference paragraph lists the size of the ASCII text file as 219KB, which should be amended to list the size in bytes (224,106 bytes).
Specification
The disclosure is objected to because of the following informalities:
The Tables at pages 59-60 and 100 are not numbered.
The use of the terms TALEN at paragraph [0321], RNEASY at paragraph [0323], TRUSEQ at paragraph [0323], HISEQ at paragraph [0323], RETRONECTIN at paragraph [0352], DYNABEADS at paragraph [0352], and XENOGEN at paragraph [0353], which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear 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.
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 196-200 and 209-213 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 196 recites the limitation "the transcriptional repressor domain" in line 17. There is insufficient antecedent basis for this limitation in the claim.
Claims 197-200 depend from claim 196, and are therefore included in this rejection.
Claim 209 recites the limitation "the transcriptional repressor domain" in line 17. There is insufficient antecedent basis for this limitation in the claim.
Claims 210-213 depend from claim 196, and are therefore included in this rejection.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 196-208 are rejected under 35 U.S.C. 103 as being unpatentable over Urnov et al. (PCT Patent Application Publication No. WO 2019/204643, published October 24, 2019, filed April 18, 2019, and claiming priority to U.S. Provisional Patent Application Nos. 62/819,237; 62/738,825; 62/716,223; 62/690,905; and 62/659,656; filed March 15, 2019; September 28, 2018; August 8, 2018; June 27, 2018; and April 18, 2018, respectively, and cited in the Information Disclosure Statement filed August 29, 2022) in view of Agrawal et al. (U.S. Patent No. 9,828,601) and Bonas et al. (PCT Patent Application Publication No. WO 2012/104729, published August 9, 2012, and cited in the Information Disclosure Statement filed March 27, 2024).
Regarding claims 196 and 201, Urnov discloses polypeptides and nucleic acid encoding the polypeptides that include a DNA binding domain, and which include repeating units derived from repeat units in proteins from animal pathogens (abstract). Urnov discloses that the repeating units each bind to a single nucleotide or base pair (paragraph [0005]). Urnov discloses the formula for the repeating units , with X1-11 being 11 contiguous amino acids, X12-33, 34, 35, being 20, 21, or 22 contiguous amino acids, and X12-X13 being HK, HD, HA, HN, HG, NN, NG, RN, HI, HV, RT, SN, HS, GS, or LN (paragraphs [0005]-[0013]).
Regarding claim 203 and 206, Urnov discloses that the nucleic acid binding domain can be a modular animal pathogen derived nucleic acid binding domain (MAP-NBD) and indicates that the plurality of repeat units can be rearranged/replaced with other repeat units and cab be arranged in an order such that the nucleic acid binding domain binds to the target nucleic acid (paragraph [0047]). Urnov discloses that any repeat unit in a modular nucleic acid binding domain can be switched with a different repeat unit (paragraph [0047]). Urnov discloses that the modularity can provide for swapping out a repeat unit for another repeat unit to increase affinity for a particular target nucleic acid, allowing for precise targeting of any nucleic acid sequence of interest (paragraph [0047]).
Urnov fails to disclose that the transcription repressor codes for TIM-3 or PD-1/PDCD1. Urnov fails to explicitly disclose the ordering of the repeat units or the location of the target sequence to which the repeat units bind.
Regarding claim 196, Agrawal discloses chimeric transcription repressors specific for the immune checkpoint molecule TIM-3 (abstract and column 10, lines 47-54). Agrawal discloses a TIM-3 specific sequence having the sequence of SEQ ID NO: 41 (Appendix I, SEQ ID NO: 396).
Regarding claim 197, Agrawal further discloses a TIM-3 specific sequence that comprises the sequence of SEQ ID NO: 42 (Appendix I, SEQ ID NO: 396).
Regarding claim 198, Agrawal further discloses a TIM-3 specific gRNA that comprises the sequence of SEQ ID NO: 43 (Appendix I, SEQ ID NO: 396).
Regarding claim 199, Agrawal further discloses a TIM-3 specific gRNA that comprises the sequence of SEQ ID NO: 44 (Appendix I, SEQ ID NO: 396).
Regarding claim 200, Agrawal further discloses a TIM-3 specific gRNA that comprises the sequence of SEQ ID NO: 45 (Appendix I, SEQ ID NO: 396).
Regarding claim 201, Agrawal discloses the transcriptional repression of PD-1 (PDCD1) (abstract and column 10, lines 14-21). Agrawal discloses that the inhibitors may be chimeric transcriptional repressors that comprise a DNA-binding domain (abstract and column 10, lines 14-21). Agrawal discloses a binding sequence that is SEQ ID NO: 1 (Appendix II, SEQ ID NO: 388).
Regarding claim 202, Agrawal discloses a binding sequence that is SEQ ID NO: 1, which comprises SEQ ID NO: 2 (Appendix II, SEQ ID NO: 388).
Regarding claim 204, Agrawal discloses a binding sequence that is SEQ ID NO: 1, which comprises SEQ ID NO: 3 (Appendix II, SEQ ID NO: 388).
Regarding claim 205, Agrawal discloses a binding sequence that is SEQ ID NO: 1, which comprises SEQ ID NO: 4 (Appendix II, SEQ ID NO: 388).
Regarding claim 207, Agrawal discloses a binding sequence that is SEQ ID NO: 1, which comprises SEQ ID NO: 5 (Appendix II, SEQ ID NO: 388)
Regarding claim 208, Agrawal discloses a binding sequence that is SEQ ID NO: 1, which comprises SEQ ID NO: 6 (Appendix II, SEQ ID NO: 388).
Bonas discloses DNA binding domains based upon a TALE and how to design such binding domains (page 19, line 23 to page 20, line2).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Agrawal’s transcriptional repressor domains of TIM-3 and PD-1/PDCD1 and including the DNA binding domains having the repeat domains of Urnov in order to provide a nucleic acid that encodes a polypeptide comprising a DNA-binding domain, which can be prepared according to the disclosure of Bonas. One of ordinary skill in the art would have been motivated to provide the nucleic acid according to Urnov in view of Agrawal and Bonas in order to control expression and/or repression of a variety of genes in a subject, and which can be used in therapeutic applications based on conditions related to expression and/or repression of genes TIM-3 and PD1/PDCD1 of Agrawal in combination with the DNA binding domains having the repeat units of Urnov.
It would also have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to employ the modularity of Urnov’s repeat units to arrive at the specific ordering of the repeat units, including the location that the repeat unit binds to, using Agrawal’s binding sequences for PD1/PDCD1 because, as disclosed by Urnov, the repeat units can be arranged in whatever order is desired in order to more effectively target a particular nucleic acid sequence, including those disclosed by Agrawal. One of ordinary skill in the art would have been motivated to arrange the repeat units in the claimed order because this provides for a more efficient and effective targeting of a specific nucleic acid sequence.
Claims 209-213 are rejected under 35 U.S.C. 103 as being unpatentable over Urnov et al. (PCT Patent Application Publication No. WO 2019/204643, published October 24, 2019, filed April 18, 2019, and claiming priority to U.S. Provisional Patent Application Nos. 62/819,237; 62/738,825; 62/716,223; 62/690,905; and 62/659,656; filed March 15, 2019; September 28, 2018; August 8, 2018; June 27, 2018; and April 18, 2018, respectively, and cited in the Information Disclosure Statement filed August 29, 2022) in view of Triebel et al. (171 Journal of Experimental Medicine 1393-1405 (1990), Kuchroo et al. (PCT Patent Application Publication No. WO 2017/069958, published April 27, 2017, and cited in the Information Disclosure Statement filed March 27, 2024) and Bonas et al. (PCT Patent Application Publication No. WO 2012/104729, published August 9, 2012, and cited in the Information Disclosure Statement filed March 27, 2024).
Regarding claim 209, Urnov discloses polypeptides and nucleic acid encoding the polypeptides that include a DNA binding domain, and which include repeating units derived from repeat units in proteins from animal pathogens (abstract). Urnov discloses that the repeating units each bind to a single nucleotide or base pair (paragraph [0005]). Urnov discloses the formula for the repeating units , with X1-11 being 11 contiguous amino acids, X12-33, 34, 35, being 20, 21, or 22 contiguous amino acids, and X12-X13 being HK, HD, HA, HN, HG, NN, NG, RN, HI, HV, RT, SN, HS, GS, or LN (paragraphs [0005]-[0013]).
Regarding claim 213, Urnov discloses a cell that can be a target cell (paragraphs [0160]-[0166]).
Regarding claim 209, Triebel discloses the sequence of LAG-3, which includes the sequence of SEQ ID NO: 57 (Figure 1) (Appendix III).
Regarding claim 210, Triebel discloses the sequence of LAG-3, which includes the sequence of SEQ ID NO: 58 (Figure 1) (Appendix III).
Regarding claim 211, Triebel discloses the sequence of LAG-3, which includes the sequence of SEQ ID NO: 59 (Figure 1) (Appendix III).
Regarding claim 212, Triebel discloses the sequence of LAG-3, which includes the sequence of SEQ ID NO: 60 (Figure 1) (Appendix III).
Kuchroo discloses inhibitors of the immune checkpoint molecule LAG-3 (page 8, paragraph [0041]). Kuchroo discloses that the inhibitors may be chimeric transcriptional repressors that comprise a DNA-binding domain based on a TALE (page 17, paragraphs [0107] and [0284]-[0288] and Table 1).
Bonas discloses DNA binding domains based upon a TALE and how to design such binding domains (page 19, line 23 to page 20, line2).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to substitute Triebel’s and Kuchroo’s transcriptional repressor domains of LAG-3 and including the DNA binding domains having the repeat domains of Urnov in order to provide a nucleic acid that encodes a polypeptide comprising a DNA-binding domain, which can be prepared according to the disclosure of Bonas. One of ordinary skill in the art would have been motivated to provide the nucleic acid according to Urnov in view of Triebel, Kuchroo, and Bonas in order to control expression and/or repression of a variety of genes in a subject, and which can be used in therapeutic applications based on conditions related to expression and/or repression of genes LAG-3 of Triebel and Kuchroo in combination with the DNA binding domains having the repeat units of Urnov.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636