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 .
Election/Restrictions
Claim 70 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected apparatus, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/14/2026.
Drawings
The drawings are objected to because the some of the axes in figures 9-12 are unreadable. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
While it is noted that “http” exists in the text patent application, this is not associated with any hypertext or links. As such, there is no need to object to this.
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 20 and 22-26 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 20 is indefinite because it is unclear how the processor “determines” an enzyme concentration, and what criteria are used to make this determination. If a claim is drawn to a mathematical determination, the claim should include some form of equation or algorithm to inform the artisan how the claimed determination is performed.
Claims 22 and 23 are rejected because it is unclear how the system determines these values then applies them.
Claims 24-26 are rejected insofar as they claim dependence on claim 20, but do not remedy the above-described indefiniteness.
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 2 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. Flow injection analyzers are either sequential or direct. Since the limitation defines the two varieties of flow injection analyzer, it does not further limit the parent claim, since these would already be included in the limitation of the parent claim. 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 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.
Claims 1, 2, 8-10, 12, 16, 17, 20, 22-27, 49-51, and 67 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claim(s) recite(s) a method of detecting post-translational modification in a protein, using a flow injection analyzer. This judicial exception is not integrated into a practical application because the method provides for steps of using a routine and conventionally used apparatus to measure post-translational modification in a protein. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims provide for a combination of mental steps, and steps used on a widely used apparatus, without informing the skilled artisan what to do with the acquired data.
For the analysis of the claims, under 35 USC 101, the Applicant is directed to MPEP 2106, particularly the flow chart provided in section III. The first step of the flow chart asks if the claims are drawn to one of the statutory categories. Since the claims are drawn to a method, the answer is “yes,” and we can move to step 2A. The next step asks of the claims are drawn to an abstract idea. There are four main types of limitation in the claims: “receiving,” “delivering,” “transferring,” and “detecting.” While all of these can be considered active steps, it is clear that these are automated steps that are performed on a flow injection analyzer. Since there is no clear transformation claimed, and merely transferring materials from one location to another, the method appears to convey an abstract idea drawn to an algorithm for operating a flow injection analyzer. Therefore, step 2A is answered “yes.” The next step is to determining if the claims encompass significantly more than the judicial exception. In order to determine this step, the claims must be analyzed to determine if the steps and apparatus can be considered routine and conventionally used apparatuses, and thusly, methodology. See MPEP 2106.05(d).
The claims are drawn to a method of detecting post-translational modification by applying sample protein to a flow injection analyzer. For all intents and purposes, a flow injection analyzer can be considered an automated liquid chromatograph, that also can also be coupled to a mass spectrometer. See Virag, et al (Chromatographia, 83, 1-10, 2020), page 1, “Abstract” section; Fransson, et al (US Pat.6,354,145), column 1, lines 11-15; column 3, lines 14-23; instant specification, page 20, lines 11-22. Since all steps are performed on the analyzer, wherein steps that follow administration to the analyzer are generally automated, the claimed steps would have necessarily been encompassed by the general operation of the analyzer. Therefore, applying these steps to a flow injection analyzer would be considered well-understood, routine, and conventional. In fact, although Virag does not explicitly teach a flow injection analyzer, Virag is clear that post-translation modifications can be analyzed using liquid chromatography coupled to a mass spectrometer. See pages 3-6, “Principles and Trends in Mass Spectrometry-Based PTM Mapping” section and “Mass Spectrometric Analysis of the Most Frequent Post-translational Modifications” section; page 5, figure 2. Therefore, specifically applying a flow injection analyzer, or functional equivalent, to analyze post-translational modification of a protein would be considered routine and conventional.
Given that all of the steps can be automated on a conventionally used system, the claims as a whole must be considered routine and conventional; as such, the independent claims are ineligible under 35 USC 101. When looking at the dependent claims, they further define method steps that directly apply to the automation of the flow injection analyzer, or are drawn to sample preparation. With respect to the former, these would be consistent with the above-described conventionally used apparatus, and do not provide for significantly more than the judicial exception. With respect to the latter, sample preparation is also a routine and conventional activity, that was also described by Virag, indicating that protein digesting, for example, is a necessary step for detecting post-translational modification of the protein. See VIrag, page 4, left column, first [full] paragraph; page 5, figure 2; page 7, left column, second paragraph.
Claim Rejections - 35 USC § 102/103
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 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.
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 1, 2, 8, 9 and 12 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Virag, et al (Chromatographia, 83, 1-10, 2020), and evidenced by Fransson, et al (US Pat.6,354,145). Virag teaches methods of analyzing post-translational modifications of proteins. See page 1, “Abstract” section. The claimed detecting and the analyzing of Virag are considered to be the same. Virag shows a flow chart of the generalized method of analyzing post-translational medication, wherein there are steps of “receiving,” “delivering,” and “transferring.” See page 5, figure 2. Although Virag does not explicitly teach providing a second sample, these systems were designed for multiple samples to be stored in a sample tray, prior to operation. Although the chromatography of Virag is literally an analysis of an injected sample by providing a flowing liquid phase, Virag does not state the term “flow injection analyzer.”
Fransson provides for a flow injection analyzer and indicates that these can be either considered the same as liquid chromatographers or are, at least, obvious variants of the chromatographic apparatuses described in Fransson. See column 1, lines 10-18. Fransson also provides for generalized method steps that overlap with the flow chart of Virag and the claimed steps. column 3, lines 8-33. Since there is a clear methodological overlap between the chromatographic steps of Virag and the flow injection analyzer steps of Fransson, it can be assumed that the chromatographic apparatus of Virag is the same as the flow injection analyzer of Fransson and that claimed. If the Applicant can provide reasonable evidence that these are different apparatuses, it would be reasonable to suggest that Fransson shows that the claimed flow injection analyzer is an obvious variant of the chromatographic apparatus of Virag, wherein the ordinary artisan would find the exchange of one device for another to provide for the same, or predictable results.
With respect to claim 1, Virag appears to anticipate the claimed method. If it can be shown that Virag does not anticipate the claimed method, the ordinary artisan would find the claimed method obvious over Virag. Furthermore, as discussed above, the claimed steps are generally automated within a flow injection analyzer/liquid chromatogram, and as such, would be automatically be performed by the apparatus.
With respect to claim 2, Virag teaches a flow analyzer that is consistent with the claimed analyzer. Since the prior art discloses the claimed flow analyzer, it would necessarily include the two different types of flow analyzer. However, if Virag does not anticipate the claimed method, both of the flow analyzer apparatuses would be considered obvious to use. There is nothing unexpected or unpredictable about their operation.
With respect to claims 8 and 9, the instant claim is generally describing the control of flow rate. This exists on all flow-type chromatographic devices and is fully controlled by the artisan prior to sample insertion.
With respect to claim 12, Virag teaches enzymatic digestion of the eluate by means of proteolytic protein, like trypsin, Asp-N and Glu-C. See page 5, Figure 2.
Claim Rejections - 35 USC § 103
Claims 16, 17, 22-27, 49-51 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Virag, et al (Chromatographia, 83, 1-10, 2020), and evidenced by Fransson, et al (US Pat.6,354,145). See the discussion of Virag and Fransson above.
With respect to claim 10, although Virag does describe mass spectrometry as the means of detecting the proteins, Fransson indicates that UV detectors are routine. See column 3, line 17. The ordinary artisan possesses either a PhD or Masters in proteomics, or a related field, and would find the exchange of different detectors to be obvious, and provide for predictable types of data. See MPEP 2141.03.
With respect to claims 16 and 17, based upon Virag’s flow chart, it appears as though Virag performs these steps. See page 5, Figure 2. Although Virag does not state incubation or the pH of the incubation step, the ordinary artisan is well-aware of protein kinetics, and that they behave more efficiently when provided with physiological temperatures and pH’s.
With respect to claims 20, 22 and 23, as discussed above, Virag explicitly teaches digesting the proteins with enzymes. Although Virag does not state any ratios of proteolytic enzymes, enzyme kinetics are highly predictable, and the ordinary artisan would be capable of optimizing the proteolytic enzyme level, based on any given enzyme.
With respect to claims 24-27, although Virag does not explicitly teach temperatures, the ordinary artisan is well-aware that proteolytic enzymes of a particular temperature window, wherein they have the greatest efficiency. The ordinary artisan is wholly capable of choosing an appropriate proteolytic enzyme, and applying a temperature that is ideal for that particular enzyme. Since these enzymes are commercially sold, with their temperature kinetics printed on the sales literature, this would be obvious.
With respect to claims 49 and 50, Virag generally describes the apparatus and the claimed limitations. The ordinary artisan would find these steps obvious, because they are applying them to a well-known and widely-used apparatus, to perform a method that has been described previously.
With respect to claim 51, although Virag does not state incubation or the pH of the incubation step, the ordinary artisan is well-aware of protein kinetics, and that they behave more efficiently when provided with physiological temperatures and pH’s.
With respect to claim 67, although Virag does not explicitly teach temperatures, the ordinary artisan is well-aware that proteolytic enzymes of a particular temperature window, wherein they have the greatest efficiency. The ordinary artisan is wholly capable of choosing an appropriate proteolytic enzyme, and applying a temperature that is ideal for that particular enzyme. Since these enzymes are commercially sold, with their temperature kinetics printed on the sales literature, this would be obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID W BERKE-SCHLESSEL whose telephone number is (571)270-3643. The examiner can normally be reached M-F 8AM-5:30PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651