DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment filed September 17, 2025, has been received and entered.
Claim 2 is cancelled.
Claims 1 and 3-8 are pending. Claim 8 is withdrawn.
Claims 1 and 3-7 are examined on the merits.
Claim Objections
Claims 1 and 3-7 are objected to because of the following informalities:
Claim 1 is objected to because it recites “a step B of mixing the the supernatant.” The second “the” should be deleted.
Also, claim 1 is objected to because the recitation “wherein the step C is performed between the step A and the step B” in the last two lines is redundant. Prior to this recitation, an order of the steps is recited that makes clear that step C is between step A and step B. Therefore, the recitation “, wherein the step C is performed between the step A and the step B” in the last two lines should be deleted.
Since claim 1 is objected to, then its dependent claims, claims 3-7, are objected to.
Claim 3 is objected to because it recites “speration” in line 4 which is a misspelling of the word “separation.”
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.
Claim 6 is 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 6 is rendered indefinite by the recitation “the sample in the step A contains the reducing agent…prior to a start of the step A” in lines 3-5. It is confusing how the sample contains the reducing agent since the sample is distinct from the reducing agent of reagent A. It is unclear whether the limitation is requiring that the sample comprises the reducing agent in addition to the reducing agent immobilized on the support of reagent A. The recitation “prior to a start of the step A” appears to suggest that the reducing agent is in the sample in addition to the immobilized reducing agent of reagent A, since the sample had not been mixed with reagent A prior to the start of step A. However, that interpretation would not be supported by the specification. In particular, paragraph [0042] of the specification discloses the claimed ratio of reducing agent to disulfide bonds in the sample (two equivalents to 1,000,000 equivalents of the reducing agent) in terms of the amount of the reducing agent contained in the reagent A to disulfide bonds in the sample.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 fails to further limit the subject matter of claim 1. Claim 3 sets forth the same order of steps A, B, C and the associated separation step of step C (step X-C) as set forth in claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Interpretation
Regarding claim 6, the limitation of lines 3-5 is being interpretated as follows; the reagent A contains the reducing agent in an amount of two equivalents to 1,000,000 equivalents per equivalent of disulfide bonds in the sample when added in step A
Relevant Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Regnier (US 2002/0037532) discloses a method for protein identification and quantification in complex mixtures, in which peptides are derived that can be analyzed by mass spectrometry (paragraphs [0013], [0019], and [0020]; abstract). Proteolytic cleavage is performed which can be by enzymatic means (paragraph [0017]). The proteolytic agent can be immobilized on a support (paragraph [0062]). For instance, Regnier teaches an immobilized enzyme column (paragraphs [0076] and [0176]). Therefore, Regnier teaches reagent B of step B of instant claim 1.
Prior to proteolytic cleavage, the proteins are preferably alkylated with an alkylating agent in order to prevent the formation of dimers or other adducts through disulfide/dithiol exchange; optionally, the proteins are reduced prior to alkylation in order to facilitate the alkylation reaction and subsequent fragmentation (paragraph [0018]). This is relevant to the claimed invention since instant claim 1 includes a step A using a reducing agent (which the reduction of Regnier to relevant to), followed later by a step C using an alkylating agent (which the alkylation of Regnier is relevant to), and a step B performed later than steps A and C which uses an enzyme (which the proteolytic cleavage of Regnier is relevant to). Regarding alkylation, Regnier teaches that in one embodiment, the alkylating agent is immobilized on a suitable substrate, and the protein or peptide mixture is contacted with the immobilized alkylating agent to select cysteine-containing peptides or proteins (paragraph [0075]). If proteins are selected, proteolysis can be conveniently carried out on the immobilized proteins to yield immobilized cysteine-containing peptides (paragraph [0075]). Selected peptides or proteins are then released from the substrate and subjected to further processing in accordance with the method of the invention of Regnier (paragraph [0075]). The immobilized alkylating agent of Regnier is directed to reagent C of step C of instant claim 1. However, Regnier differs from the claimed invention with respect to the claimed step B in that Regnier fails to disclose mixing a supernatant separated from reagent C (the immobilized alkylating agent of Regnier) with their proteolytic agent (which can be an enzyme immobilized on a support) which is directed to the claimed reagent B. Instead, the proteins immobilized onto Regnier’s reagent C (the immobilized alkylating agent) are treated to proteolysis (e.g., by enzymatic means), as indicated in paragraph [0075].
Response to Arguments
Applicant’s arguments, filed September 17, 2025, with respect to the objection to claims 1 and 3-7, the rejections under 35 U.S.C. 112(b) of claims 1 and 3-7, the rejection under 35 U.S.C. 112(d) of claim 3, the rejection under 35 U.S.C. 103 of claims 1 and 3-7 as being unpatentable over Vale in view of Zwyssig and Zhang, and the rejection under 35 U.S.C. 103 of claim 6 as being unpatentable over Vale, Zwyssig, and Zhang in further view of Tzanavaras and Jeng, have been fully considered and are persuasive.
In particular, the claim objection has been overcome by the amendment to claim 1. The rejections under 35 U.S.C. 112(b) have been overcome by the amendments to claims 1, 3, and 6. The rejection under 35 U.S.C. 112(d) has been overcome by the amendment to claim 3. The rejections under 35 U.S.C. 103 have been overcome by the amendment to claim 1. In particular, the cited prior art fails to render obvious the limitation of step B of claim 1 of mixing the supernatant obtained in step X-C and a reagent B containing a support and an enzyme immobilized on the support. Zhang had been cited in the last Office Action to render obvious limitations of steps C, X-C, and B of claim 1. However, Zhang discloses that their reagent C (solid phase alkylation reagent), as opposed to the supernatant obtained from their centrifugation after treatment with their reagent C, was mixed with trypsin (see discussion of Zhang in the paragraph bridging pages 11 and 12 of the last Office Action). Thus, Zhang is contrary to the limitation of step B of mixing the supernatant obtained in step X-C and a reagent B.
Therefore, the claim objection and these rejections have been withdrawn.
However, upon further consideration, a new ground(s) of rejection is made in view of the amendments to claims 1, 3, and 6.
Conclusion
Claims 1, 4, 5, and 7 allowed.
Claims 3 and 6 are not allowed.
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.
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/SUSAN E. FERNANDEZ/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651