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 .
DETAILED ACTION
1. The Applicant’s response to the office action filed on November 03, 2025 is acknowledged.
Status of the Application
2. Claims 1-5 and 7-10 are pending under examination. Claim 6 is cancelled. The Applicant’s arguments have been fully considered and found persuasive in-part for the following reasons.
Objection to the Specification-withdrawn
3. The objection to the specification has been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 102-withdrawn
4. The rejection of claims under 35 USC 102(a)(1) as being anticipated by Volden et al. has been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 103-Maintained
5. 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.
Claims 1-5 and 7-10 are rejected under 35 U.S.C. 103 as being unpatentable over Volden et al. (BioRxiv, page 1-31, published on June 4, 2018) in view of Brown et al. (WO 2017/139681).
Volden et al teach an immune cell ribonucleic acid (RNA) sequencing method of claim 1, comprising: producing a circularized DNA comprising a complementary DNA (cDNA) and a known heterologous sequence (known sequence, adapter or barcode), wherein the cDNA is produced from an immune cell RNA; performing rolling circle amplification using the circularized DNA as template to produce a concatemer comprising repeating segments comprising the cDNA and the known heterologous sequence; and sequencing the concatemer or fragments thereof (page 19-21, paragraphs under subheads ‘single B cell lysates’; ‘DNA splint amplification’; R2C2 sample preparation’; Rolling circle amplification’; and ‘ONT sequencing’; page 4, paragraph 1, under subheading ‘results on page 4-5).
With reference to claim 2, Volden et al. teach that the cDNA is produced from an immune cell RNA that encodes an antibody heavy chain, an antibody light chain, or a chain of a T cell receptor (page 19, paragraph under subheading ‘single cell B cell lysate’, page 4, paragraphs under subheading ‘results on page 4-5).
With reference to claim 3-4, Volden et al. teach that the sequencing is by single molecule sequencing and the sequencing comprises sequencing fragments of the concatemer (page 21, paragraph under subheading ‘ONT sequencing’).
With reference to claim 5, Volden et al. teach that the method further comprising, subsequent to performing rolling circle amplification, tagmenting the concatemer to produce the fragments (page 10, paragraph under subheading ‘R2C2 allows the demultiplexing of 7-8 nt cellular indexes).
With reference to claim 7-8, Voden et al. teach that the cDNA encodes an antibody chain, and wherein the method further comprises typing the antibody chain based on the sequencing or encodes a chain of a T cell receptor, and wherein the method further comprises typing the chain of the T cell receptor based on the sequencing (page 13, paragraphs under subheading ‘R2C2 identifies isoforms in single human B cells’).
However, Volden et al. did not specifically teach RNA enconding an HLA and typing the HLA based on RNA sequencing.
Brown et al teach ribonucleic acid (RNA) sequencing method comprising: RNA that encodes a human leukocyte antigen (HLA) and cDNA sequencing and thereby typing HLA alleles (para 00152-00153, 0084-0086, 0071).
It would have been prima facie obvious to an ordinary person skilled in the art before the effective filing date of the invention to modify the method of Volden et al. with the inclusion of HLA typing as taught by Brown et al. to develop an improved method of HLA sequencing. The ordinary person skilled in the art would have motivated to combine the method of Volden with the sequence-based HLA typing as taught by Brown et al. and have a reasonable expectation of success that the combination would result in an improved method because Brown et al. explicitly taught RNA sequence-based HLA typing (para 00152-00153, 0084) and such a modification is considered obvious over the cited prior art.
Response to Arguments:
With reference to the rejection of claims under 35 USC 103 as being unpatentable over Volden et al. in view of Brown et al., the Applicant’s arguments and the amendment have been fully considered and found unpersuasive. With reference to the Applicant’s arguments drawn to genotyping HLA genes and no motivation to combine the method of Volden with the method of HLA typing as taught by Brown et al., the Applicant’s arguments were found unpersuasive. Brown et al. teach RNA products that encode HLA gene (para 00152-0153) and sequencing based HLA typing, which is within the scope of the claims and as discussed in the rejection it would be obvious to modify the method of Volden with the sequencing of RNA products that encode an HLA and HLA typing based on sequencing as taught by Brown et al. For all the above, the rejection has been maintained and restated to address the amendment.
New Rejections Necessitated by the Amendment
Claim Rejections - 35 USC § 112
6. 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 2 and 7-8 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. The claims 2 and 7-8 recite that the cDNA is produced from an immune cell RNA that encodes an antibody or a T cell receptor. The limitations are unclear and indefinite because the claim 1 upon which the claims 2, 7-8 depend requires an immune cell RNA that encodes an HLA and it is not clear how the RNA that encodes an HLA would encode for an antibody or a T-cell receptor.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SURYAPRABHA CHUNDURU whose telephone number is (571)272-0783. The examiner can normally be reached 8.00am-4.30pm.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681