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 .
Applicant previously cancels claims 17-18. Claims 1-16 and 19-22 are currently pending and under examination.
Information Disclosure Statement
The Information Disclosure Statements filed September 20, 2023; July 02, 2024; September 15, 2024; May 02, 2025; and May 02, 2025 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/patents-application- process/filing-online/legal-framework-efs-web), 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 1.834(c)(1),
1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete.
Required response – Applicant must:
Include a Sequence Listing Incorporation by Reference paragraph at page 1 of the
specification. The Sequence Listing Incorporation by Reference paragraph should list the size of the ASCII text file as 794 bytes.
Specification
The use of the terms Illumina®, 454TM , 454 Life SciencesTM , AMPure® and ION TORRENTTM , Agilent Bioanalyzer® and RipTide® (see Page 3, [0013], Page 7, [0039], Pages 11-12, [0066]-[0068], Page 13, [0074], Page 15, [0084], Page 17, [0090], Pages 23-24, [00116]-[00117] and Page 33, [00164]), which are trade names or a marks used in commerce, has been noted in this application. The terms 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.
Claim Objections
Claims 1- 3 are objected to because of the following informalities:
In claim 1, line 5, “capable of binding to each” should read “that bind to each”.
In claim 2, line 1, “wherein the each nucleic acid” should read “wherein each nucleic acid”.
In claim 3, lines 1-2, ““wherein the each nucleic acid” should read “wherein each nucleic acid”.
Additionally, in claim 3, line 2, “is a cDNA” should read “is a complementary deoxyribonucleic acid (cDNA)”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 19 is 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 instant specification does not provide support for the invention as claimed. Instant claim 19 recites the limitation, wherein the capture agent comprises a polycarbonate or a polypropylene surface. While the specification does disclose several capture agents as well as support with a surface, the specification does not disclose the capture agents or a surface comprising polycarbonate or polypropylene.
Claims 1-16 and 19-22 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 1 is considered vague and indefinite for the following reasons:
Claim 1 recites the limitation "the product of (a)" in line 7. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites the limitation "the product of (b)" in line 9. There is insufficient antecedent basis for this limitation in the claim.
Claims 2-16 and 19-22 depend from claim 1 and are therefore included in this rejection.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-15 and 20-22 are rejected under 35 U.S.C 102 (a)(2) as being
anticipated by Tori et al. (U.S. Patent Application Publication US 2022/0348999 A1,
published November 03, 2022, effectively filed December 04, 2019).
Regarding claim 1, Tori teaches a method of normalizing a population of nucleic acid samples (Page 2, [0016]). Tori teaches contacting a plurality of nucleic acid samples to a normalizing agent (Page 8, [0052], Page 11, [0071] and Examples 1-3 and 6-7). Tori teaches each nucleic acid of the plurality comprises a sample-specific barcode and the normalizing agent comprises a plurality of labeled enzymes capable of binding to each sample-specific barcode (Page 8, [0052], Pages 12-13, [0076]-[0077]). Tori teaches contacting the product of (a) to a capture agent to capture the nucleic acids that are bound to the normalizing agent (Page , [0072] [0029] [0041] and [0043]). Tori teaches treating the product of (b) with a protease to release the bound nucleic acids, thereby creating a normalized library having more even representation of each nucleic acid sample than the plurality of nucleic acid samples before normalization (Pages 7-8, [0050]-[0052] and Page 3, [0025]).
Regarding claim 2, Tori teaches each nucleic acid of the plurality is a deoxynucleic acid (DNA) (Page 3, [0026]).
Regarding claim 3, Tori teaches each nucleic acid of the plurality is a cDNA (Page 9, [0061] and Page 12, [0075]).
Regarding claim 4, Tori teaches each nucleic acid of the plurality is double stranded (Page 3, [0026]).
Regarding claim 5, Tori teaches each nucleic acid of the plurality is single stranded (Page 3, [0026]).
Regarding claim 6, Tori teaches the normalizing agent comprises a nuclease (Page 4, [0032]).
Regarding claim 7, Tori teaches the nuclease is a RNA guided nuclease (Page 6, [0043], Page 8, [0052], and Page 11, [0071]).
Regarding claim 8, Tori teaches the nuclease is a Cas nuclease (Page 4, [0032]-[0033] and Page 8, [0052]).
Regarding claim 9, Tori teaches the nuclease is a Cas9 nuclease (Page 4, [0032]-[0033] and Page 8, [0052]).
Regarding claim 10, Tori teaches the nuclease is a dCas9 nuclease (Examples 1 and 6).
Regarding claim 11, Tori teaches the normalizing agent comprises a deactivated enzyme (Examples 1 and 6).
Regarding claim 12, Tori teaches the protease is a proteinase K (Pages 7-8, [0050]).
Regarding claim 13, Tori teaches the plurality of labeled enzymes comprises biotin (Page 5, [0042]-[0042] and Page 11, [0072]).
Regarding claim 14, Tori teaches the capture agent is streptavidin, a bead, or a magnetic bead (Page 3, [0029], Page 5, [0041] and Page 11, [0072]).
Regarding claim 15, Tori teaches the capture agent is an antibody (Page 5, [0041], Page 7, [0047] and [0049]).
Regarding claim 20, Tori teaches the normalizing agent comprises an equimolar amount of each enzyme binding to each individual barcode (Page 8, [0052] and Page 3, [0025]).
Regarding claim 21, Tori teaches the plurality of nucleic acid samples comprises a plurality of libraries derived from different samples (Page 3, [0026], Page 8, [0055] and Abstract).
Regarding claim 22, Tori teaches the method is completed in a single tube (Page 8, [0053]).
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.
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 3 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Tori et al. (U.S. Patent Application Publication US 2022/0348999 A1, published November 03, 2022, effectively filed December 04, 2019), as applied to claims 1-15 and 20-22 above, and in view of Zhang et al. (People’s Republic of China Application Publication CN 105793425 A, published July 20, 2016).
Regarding claim 16, Tori teaches the antibody as discussed above.
Regarding claim 19, Tori teaches the capture as discussed above.
Tori does not teach or suggest the antibody is specifically a CAS antibody. Tori does not teach or suggest the capture agent comprises a polycarbonate or a polypropylene surface.
Zhang teaches normalizing a nucleic acid population (Page 141, Second Paragraph, Page 155, Fifteenth Paragraph, Page 184, Second to Last Paragraph, Page 185, Whole Page, Page 187, Sixth Paragraph, Page 188, Fourteenth Paragraph). Zhang teaches a normalizing agent that is Cas9 and dCas9 as well as RNA guided nuclease (Page 26, Fifth Paragraph, Page 31, Third Paragraph and Page 37, Fourth-Fifth Paragraph). Zhang teaches the normalizing agent comprises a plurality of labeled enzymes capable of binding to each sample-specific barcode in equimolar amounts (Page 213, Third Paragraph and Page 231, First Paragraph). Zhang teaches treating the nucleic acids with proteinase K to release bound nucleic acids (Page 211, Last Paragraph and Page 228, Fourth Paragraph). Zhang teaches using AMPure® beads as a capture agent (Page 228, Last Paragraph). Zhang teaches the nucleic acids are DNA and/or cDNA, double and/or single-stranded (Page 101, First Paragraph, Page 228, Last Paragraph, Page 12, Fifth Paragraph, and Page 28, Third Paragraph). Zhang teaches any one or more element may individually provided in a tube (Page 121, Fifth Paragraph). Zhang teaches labeled enzymes comprising biotin (Page 74, Third Paragraph). Zhang teaches the capture agent comprises polycarbonate and/or polypropylene (Page 58, First Paragraph, Page 65, Last Paragraph—Page 66, Second Paragraph and Page 176, Ninth-Tenth Paragraph). Zhang teaches the antibody is a CAS antibody (Page 29, Fourth Paragraph, Page 40 , Fifth Paragraph, Page 47, Fourth-Seventh Paragraph, Page 74, Third Paragraph, Page 80, Last Paragraph and Page 198, Seventh Paragraph). Zhang teaches using these methods allows for improved modifying of target polynucleotides as well as improved target specificity (Page 4, Last Four Paragraphs).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have modified the teachings of Tori with the teachings of Zhang to use a CAS antibody as well as a capture agent comprising polycarbonate or polypropylene. Using these methods would allow for improved modifying of target polynucleotides as well as improved target specificity as taught by Zhang (Page 4, Last Four Paragraphs).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached Mon - Friday 7:30-5:00 Eastern with alternate Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684