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 .
Priority
Acknowledgment is made of applicant's claim for foreign priority based on applications filed in the United Kingdom on August 14, 2020 and July 21, 2021. It is noted, however, that applicant has not filed a certified copy of these applications as required by 37 CFR 1.55.
Specification
The disclosure is objected to because of the following informalities: On page 153, lines 16-17 of the substitute specification filed on August 22, 2023, the phrase “Figure 14 describes…” should be changed to –Figures 14(a)-(c) describe…-- since the drawings depict Figures 14(a)-(c).
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 28-42 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.
On line 2 of claim 28, the phrase “the levels” lacks antecedent basis. On lines 2-4 of claim 28, the phrase “measuring the levels of two or more labeled amino acid types in the sample to generate a protein or proteome signature for each specific protein or proteome in the sample” is indefinite since it is not clear how the different labeled amino acid types measured in the entire sample are distinguished as being in a specific individual protein or proteome in the sample. If the levels of the two or more labeled amino acid types are measured in the entire sample, it would seem that a single, collective measurement of each labeled amino acid type in the sample is obtained for all of the specific proteins or proteomes in the sample. Thus, it is unclear how each of the specific proteins or proteomes in the sample are distinguished from one another by the measurement of the levels of the two or more labeled amino acid types in the sample. On line 4 of claim 28, the “n-dimensional space analysis” is indefinite since it is not clear what this type of analysis entails and how it is performed in the method. In addition, the “protein or proteome signature database” recited on line 6 of claim 28 is indefinite since it is not clear whether this database is the same or different from the n-dimensional space used in the n-dimensional space analysis. According to the instant specification, the n-dimensional space analysis comprises measuring and plotting known label values of labeled amino acids in proteins or proteomes having a known protein or proteome signature as a function of the known protein’s or proteome’s concentration, wherein the known protein or proteome signatures are represented as a line in the n-dimensional space, wherein n is a number of different labeled amino types that are measured in the known proteins or proteomes. The known protein or proteome signatures are not described as being in a “database” per say, but rather as being the lines in the n-dimensional space depicted in Figure 1 of the specification. The sample protein or proteome signatures for each specific protein or proteome in the sample analyzed are described as being points in the n-dimensional space depicted in Figure 1, wherein the line (i.e. known protein or proteome signature) closet to the sample points in the n-dimensional space represents the known protein or proteome that the proteins or proteomes in the sample being analyzed most closely matches. Therefore, the “n-dimensional space analysis” recited in claim 28 should be amended to describe this process so as to clarify how this type of analysis is performed and so that one of ordinary skill in the art would be able to practice the method. On line 7 of claim 28, the phrase “the number” lacks antecedent basis.
Claim 36 is indefinite since it is not clear whether each of the two or more labeled amino acid types in the sample are post-translationally modified amino acids.
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) 28, 32-34 and 39-40 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Swaminathan et al (article from Nature Biotechnology, vol. 36, no. 11, October 22, 2018, pages 1076-1082).
With regards to claim 28, Swaminathan et al teach of a method for identifying the presence of one or more specific proteins or proteomes in a sample. The method is a fluoro-sequencing method comprising selectively labeling two or more amino acid types in a sample, wherein the two or more amino acid types comprise cysteine and lysine in the proteins of the sample, immobilizing the labeled proteins on a glass surface, and imaging the labeled proteins using total internal reflection fluorescence microscopy (TIRF) to monitor decreases in each protein’s fluorescence after consecutive rounds of Edman degradation. The obtained fluorescent sequence of each protein in the sample is assigned or matched to its parent protein in a reference database. See the abstract, Figure 1, and pages 1076-1077 in Swaminathan et al. Swaminathan et al teach of the selective fluorescence labeling of cysteine and lysine amino acids (i.e. use of n labels, wherein n is two) in the proteins of the sample analyzed in the method. In addition, the total internal reflection fluorescence microscopy (TIRF) taught by Swaminathan et al can be considered an “n-dimensional space analysis” of the proteins in the sample because it delivers two dimensional images of the fluorescence measured, and the number of labeled amino acids in the sample is two. Thus, the method taught by Swaminathan et al uses an n-dimensional space corresponding to the n labeled amino acid types in the proteins of the sample. The method taught by Swaminathan et al falls within what is encompassed by claim 28 since it uses two labeled amino acids (i.e. cysteine and lysine, n labels, wherein n is two), and the TIRF microscopy delivers two dimensional images of the fluorescence, which qualifies as a n-dimensional space analysis, wherein n=2.
With regards to claim 32, the method taught by Swaminathan et al does not require separation of the labeled amino acids in the sample from unreacted label since no such separation step is disclosed by Swaminathan et al.
With regards to claim 33, the measuring of the levels of the two or more labeled amino acid types in the samples taught by Swaminathan et al comprises using a fluorescent plate reader containing a TIRF single molecule microscope stage perfusion chamber, a light source and a light detector. See Figure 1 in Swaminathan et al.
With regards to claim 34, the number n of labeled amino acid types in the method taught by Swaminathan et al is smaller than seven since two amino acid types (i.e. cysteine and lysine) are labeled in the method.
With regards to claim 39, the method taught by Swaminathan et al identifies the presence of at least two specific proteins in a sample since Swaminathan et al teach that the method allows millions of distinct peptide molecules to be sequenced in parallel, identified and digitally quantified (see the first paragraph in the left-hand column on page 1076 of Swaminathan et al), and that the method is sufficient to identify most proteins in the human proteome (see the right-hand column on page 1076 in Swaminathan et al).
With regards to claim 40, the method taught by Swaminathan et al identifies the presence of a proteome in the sample since Swaminathan et al teach that the method is sufficient to identify most proteins in the human proteome (see the right-hand column on page 1076 in Swaminathan et al).
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.
Claim(s) 35, 37-38 and 41-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Swaminathan et al (article from Nature Biotechnology, vol. 36, no. 11, October 22, 2018, pages 1076-1082). For a teaching of Swaminathan et al, see previous paragraphs in this Office action.
With regards to claim 35, Swaminathan et al fail to teach that each of tryptophan, cysteine, lysine and tyrosine are labeled in the proteins of the sample analyzed in the method. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to label each of tryptophan, cysteine, lysine and tyrosine in the proteins of the sample analyzed in the method taught by Swaminathan et al because Swaminathan et al suggest that if more amino acids besides cysteine and lysine are labeled in the proteins of the sample analyzed in the method, then most proteins in the human proteome could be identified. See the paragraph on the right-hand side of page 1076 in Swaminathan et al where it states “Monte Carlo simulations predict that the use of additional labels…should be sufficient to identify most proteins in the human proteome”.
With regards to claims 37-38, while Swaminathan et al fail to teach of converting the measured levels of the two or more labeled amino acid types into amino acid concentrations of each of the labeled amino acid types by applying a calibration factor to the measured levels of the two or more labeled amino acid types, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform this step because chemical analysis methods often convert measured chemical analytes of a sample into concentrations or amounts of the analytes using a calibration curve or calibration factor which plots or correlates measured signals of known amounts of analytes in a sample vs. the known concentrations or amounts.
With regards to claim 41, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method taught by Swaminathan et al to detect a known proteome of a cancer, of a virus, of a bacterium or of a host response to an infection because Swaminathan et al teach that the method is sufficient to identify most proteins in the human proteome (see the right-hand column on page 1076 in Swaminathan et al), and therefore, would also be able to identify proteins in one of a known proteome of a cancer, of a virus, of a bacterium or of a host response to an infection.
With regards to claim 42, Swaminathan et al fail to teach that three or more amino acid types are labeled in the method. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to label three or more amino acid types in the method taught by Swaminathan et al because Swaminathan et al suggest that if more amino acids besides cysteine and lysine are labeled in the proteins of the sample analyzed in the method, then most proteins in the human proteome could be identified. See the paragraph on the right-hand side of page 1076 in Swaminathan et al where it states “Monte Carlo simulations predict that the use of additional labels…should be sufficient to identify most proteins in the human proteome”.
Claim(s) 30-31 and 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Swaminathan et al (article from Nature Biotechnology, vol. 36, no. 11, October 22, 2018, pages 1076-1082) in view of Hesselberth (US 2015/0087526). For a teaching of Swaminathan et al, see previous paragraphs in this Office action.
With regards to claims 30-31 and 36, Swaminathan et al fail to teach that the R-group of the labeled cysteine and lysine amino acids is labeled with a fluorogenic label that becomes fluorescent only upon reaction with the R-group, and that the labeled cysteine and lysine are post-translationally modified.
Hesselberth teaches of a method for single-molecule peptide identification and sequencing. The method comprises labeling more than one type of amino acid in a protein with a distinct label that selectively labels the R group side chain characteristic for each amino acid type, attaching the labeled protein to a surface, imaging the protein, cleaving the N-terminal amino acid from the protein, imaging the protein a second time, comparing the images to one another to identify a change or absence of a change in the images, repeating the steps of the method, and determining an identity and a sequence of the protein from the identified and compared images (see paragraphs 0119-0121 in Hesselberth). Hesselberth teaches that each R group side chain of each amino acid type in a protein is labeled with a fluorogenic probe that is selective to that amino acid type and that becomes fluorescent only upon reaction with the R-group . For example, lysine side chains (i.e. R groups) are labeled with NHS-ester fluorophores, and cysteine side chains (i.e. R groups) are labeled with maleimide fluorophores (see paragraph 0149-0150 in Hesselberth). Hesselberth also teaches that the labeled amino acids of the protein analyzed in the method may be post-translationally modified amino acids (see paragraphs 0133 and 0152 in Hesselberth).
Based upon a combination of Swaminathan et al and Hesselberth, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to label the R-groups of the cysteine and lysine amino acids of the proteins analyzed in the method taught by Swaminathan et al with a fluorogenic label that becomes fluorescent only upon reaction with the R-group because Hesselberth teaches that the labeling of the R groups of distinct amino acids in a protein with different fluorogenic labels that become fluorescent only upon reaction with the R-group allows the distinct amino acids to be easily distinguished from one another in a protein identification and sequencing method. It also would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the method taught by Swaminathan et al on proteins containing post-translationally modified amino acids by labeling these types of amino acids because Hesselberth teaches that a protein identification method similar to that taught by Swaminathan et al where distinct amino acids are labeled with fluorogenic labels can be performed on proteins comprising post-translationally modified amino acids, thus allowing these types of proteins to be identified.
Allowable Subject Matter
Claim 29 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims since the closest prior art to Swaminathan et al determines the order of the protein or proteome being analyzed in the method by identifying a fluorescent sequence of each amino acid as it is cleaved from the protein or proteome during Edman degradation. Therefore, Swaminathan et al fail to teach or fairly suggest that the amino acid order of the protein is not determined prior to identifying the presence of the one of more specific proteins or proteomes in the sample.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Please make note of: Yang et al (WO 2019/217727) who teach of a method for proteome labeling; Reed et al (US 2020/0209255) who teach of a method for protein sequencing; Appel et al (US 2006/0003460) who teach of a method for comparing proteomes; and Marcotte et al (US 9,625,469) who teach of a method for identifying peptides at a single molecule level by labeling both internal and N-terminal amino acids.
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/MAUREEN WALLENHORST/Primary Examiner, Art Unit 1797 November 13, 2025