DETAILED ACTION
Preliminary Amendment filed on 07/23/2025 is acknowledged. Claims 2, 7, 9-11, 13-17, 21-22, 24-26, 28, 30, 34-40, 44-45, 48-49, and 51-100 are cancelled. Claims 1, 3-6, 8, 12, 18-20, 23, 27, 29, 31-33, 41-43, 46-47, 50 and 101 are pending in the application and are considered on merits.
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 .
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 101 is rejected under 35 U.S.C. §101 because the claimed invention is directed to a judicial exception and fails to recite an inventive concept.
The claimed invention is directed to natural phenomenon without significantly more.
Step 2A, Prong One: Judicial Exception
Claim 101 is directed to:
detecting an individual polypeptide molecule from a plurality of polypeptides at a specified sensitivity threshold (at least 60%)
Detecting a naturally occurring polypeptide molecule and evaluating the reliability or sensitivity of that detection is an observation of a natural phenomenon.
Furthermore, the claim recites a performance result (a sensitivity level) rather than a specific technological means for achieving that result, which constitutes an abstract idea of measurement and evaluation.
Step 2A, Prong Two: No Practical Integration
Claim 101 does not integrate the judicial exception into a practical application because:
it does not specify how the sensitivity is achieved,
it does not recite any particular assay, device, chemistry, or detection architecture, and
it merely claims the outcome of detecting a natural molecule at a given confidence level.
The claim therefore preempts detecting individual polypeptides at a sensitivity threshold, regardless of the technology used.
Step 2B: No Inventive Concept
Claim 101 lacks an inventive concept because:
it recites no additional technical elements beyond detection,
it relies on a numerical performance threshold rather than a technical solution,
and it does not improve an existing technological process.
Courts have held that reciting a desired result or performance metric without a specific technological implementation does not amount to significantly more than a judicial exception.
Thus, claim 101 is directed to observing a natural phenomenon using abstract performance criteria and does not recite additional elements that amount to significantly more. Accordingly, claim 101 is rejected under 35 U.S.C. §101.
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.
Claim(s) 1, 3-6, 8, 12, 18-20, 23, 27, 29, 31-33 and 50 is/are rejected under 35 U.S.C. 102(A)(1) as being anticipated by Natarajan et al. (US 2016/0238592) (Natarajan).
Regarding claim 1, Natarajan teaches a method for analyzing a polypeptide complex from a subject (abstract), comprising:
(A) providing said polypeptide complex (peptides, proteins) coupled to a capture unit immobilized to a support (solid support), wherein said polypeptide complex comprises a plurality of polypeptide molecules (par [0092] [0094]);
(B) coupling one or more reporter moieties (probe) to said polypeptide complex, wherein said one or more reporter moieties comprises a plurality of detectable labels (par [0089]);
(C) detecting one or more signals from said plurality of detectable labels (par [0095]); and
(D) subjecting said plurality of detectable labels to conditions sufficient to render at most a subset of said one or more detectable labels undetectable (par [0227]).
Regarding claim 3, Natarajan teaches that the method further comprising repeating (C) and (D) at least once until no signal is detected from said polypeptide complex (par [0227]).
Regarding claim 4, Natarajan teaches that wherein at least a subset of said plurality of polypeptide molecules in said polypeptide complex is quantified (par [0227]).
Regarding claim 5, Natarajan teaches that wherein a reporter moiety of said one or more reporter moieties is coupled to a polypeptide molecule of said plurality of polypeptide molecules (par [0227]).
Regarding claim 6, Natarajan teaches that wherein a polypeptide molecule of said plurality of polypeptide molecules comprises one or more binding units, wherein at least one binding unit of said one or more binding units is coupled to a reporter moiety of said one or more reporter moieties (par [0089]).
Regarding claim 8, Natarajan teaches that wherein said reporter moiety comprises a spacer (linker) coupled to a detectable label of said one or more detectable labels (par [0123]).
Regarding claim 12, Natarajan teaches that wherein (D) comprises removing a detectable label of said one or more detectable labels from said polypeptide complex (par [0227]).
Regarding claim 18, Natarajan teaches that wherein said polypeptide complex is a biomarker (makers, e.g., proteins) (par [0006]).
Regarding claim 19, Natarajan teaches that wherein an expression level of said biomarker is indicative of a disease or disorder (par [0113]).
Regarding claim 20, Natarajan teaches that wherein said disease or disorder is Parkinson's disease (PD), Parkinson's disease with dementia (PDD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), Alzheimer's disease (AD), Pick's disease, frontotemporal dementia (FTD), traumatic brain injury, chronic traumatic encephalopathy (CTE), Huntington's disease, fragile X syndrome, amyotrophic lateral sclerosis (ALS), cryoglobulinemia, amyloidosis, prion disease, transmissible spongiform encephalopathy, or Creutzfeldt-Jakob Disease (par [0134]).
Regarding claim 23, Natarajan teaches that wherein said expression level of said biomarker is quantified and correlated to a health assessment (par [0251]).
Regarding claim 27, Natarajan teaches that wherein said support is a bead, a polymer matrix, or an array (par [0092]).
Regarding claim 29, Natarajan teaches that wherein said capture unit is immobilized directly to said support (par [0092]).
Regarding claim 31, Natarajan teaches that wherein (C) further comprises providing a first energy source sufficient to render said one or more detectable labels optically detectable (par [0078]).
Regarding claim 32, Natarajan teaches that wherein said one or more detectable labels emit an optical signal (fluorescent signal) (par [0078]).
Regarding claim 33, Natarajan teaches that wherein said optical signal is a fluorescent signal (par [0078]).
Regarding claim 50, Natarajan teaches a method for analyzing a polypeptide complex from a subject (abstract), comprising:
(A) providing said polypeptide complex and one or more reporter moieties coupled thereto, wherein the one or more reporter moieties comprises a plurality of detectable labels (par [0089]), wherein the polypeptide complex comprises a plurality of polypeptide molecules (par [0094]);
(B) detecting one or more signals from said plurality of detectable labels (par [0095]); and
(C) subjecting said one or more detectable labels to conditions sufficient to render at most a subset of said one or more detectable labels undetectable (par [0227]).
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.
Claim(s) 46-47 and 101 is/are rejected under 35 U.S.C. 103 as being unpatentable over Natarajen et al. (US 2016/0238592) (Natarajan).
Regarding claim 46, Natarajan teaches imaging-based detection (par [0033][0040]). Imaging-based detection inherently produces signal counts corresponding to molecular frequency and distribution.
A POSITA would understand that determining number of detected signals inherently determines counts and frequency of polypeptide molecules.
Thus, Natarajan teaches that wherein said method further comprises determining a frequency of polypeptide molecule counts based at least in part on said one or more signals detected in (C).
Regarding claim 47, Natarajan teaches that wherein said expression level of said biomarker is quantified and correlated to a health assessment (par [0251]).
The expression level of the biomarker is based on said frequency of polypeptide molecule counts. Thus, Natarajan teaches that wherein said method further comprises detecting said disease or disorder in said subject based at least in part on a shift in a distribution of said frequency of polypeptide molecule counts.Regarding claim 101, Natarajan teaches a method for analyzing a polypeptide complex comprising a plurality of polypeptides of a subject at a single molecule level (par [0191]).
The phrase “detecting an individual polypeptide of said plurality of polypeptides at a sensitivity of at least 60%.” merely describes an intended result and does not further limit the steps of the method, therefore caries no weight in patentability determination. It would have been obvious to one of ordinary skill in the art to optimize the sensitivity by routine experimentation.
Claim(s) 41-43 is/are rejected under 35 U.S.C. 103 as being unpatentable over Natarajen et al. (US 2016/0238592) (Natarajan) in view of Pieken et al. (US 7,427,678) (Pieken).
Regarding claim 41, Natarajan does not specifically teach that wherein said polypeptide complex is coupled to said capture unit via a cross-linker.
However, in the analogous art of immobilizing biomolecules on a solid support, Pieken teaches that wherein said polypeptide complex is coupled to said capture unit via a cross-linker (col. 3, lines 40-44; col. 11, lines 6-25). It would have been obvious to one of ordinary skill in the art to couple the peptide complex to the capture unit via a cross-linker, in order to selectively immobilize biomolecules to the solid surface.
Regarding claim 42, Piekenteaches that wherein said cross-linker is an amine specific crosslinker (col. 17, lines 62-63).
Regarding claim 43, Pieken teaches that wherein said cross-linker is a PEG linker (col. 17, line 62-63).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to XIAOYUN R XU, Ph. D. whose telephone number is (571)270-5560. The examiner can normally be reached M-F 8am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at 571-272-1254. 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.
/XIAOYUN R XU, Ph.D./ Primary Examiner, Art Unit 1797