DETAILED ACTION
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 .
Applicant's arguments filed April 13, 2026 have been fully considered but they are not persuasive. Applicant has amended independent claim 1 to recite an elution buffer having a pH ranging from 1 to 3, and argued that the combination of O’Connor et al., in view of Goerke et al., do not meet the claim limitations. The Examiner respectfully disagrees.
With respect to reference to O’Connor et al., Applicant has argued that the reference teaches utilizing aprotinin as a protease inhibitor, and eluting antibodies in a pH range of 5 to 8. The Examiner notes that O’Connor et al., do not teach aprotinin in an elution buffer, but instead teaches utilizing aprotinin in a harvesting step that does not require the elution buffer taught by the reference. As stated in the previous Office action, reference to O’Connor et al., teach an elution buffer comprising acetic acid and TCEP wherein the elution buffer has a pH ranging from 2 to 5, which encompasses the claimed buffer having a pH ranging from 1 to 3.
With respect to reference to Goerke et al., Applicant has argued that the reference teaches eluting a sample at a pH ranging from 7 to 9, and therefore cannot be relied upon. The Examiner notes that reference to Goerke et al., is cited for teaching aprotinin in an elution buffer, and not the pH of the buffer itself as that limitation is met by reference to O’Connor et al. Also, the Examiner notes that the claims are directed to the elution buffer itself, thus patentability is determined based on the components of the buffer and not the manner in which it is utilized. Given this view, the Examiner contends that the combination of O’Connor et al., in view of Goerke et al., as the references in combination teach all the elements of the claimed elution buffer.
Finally, the Examiner acknowledges Applicant’s submission of evidence showing that aprotinin-protease complexes dissociate at a pH greater than 10 and less than 3. The Examiner notes that this teaching indicates that aprotinin still functions as a protease inhibitor at a pH of 3, which is within the pH range recited in the claims. As such, Applicant’s argument that aprotinin requires a pH greater than 3 to function as a protease inhibitor is not persuasive. Therefore, in light of the teachings of the prior art, and the arguments provided here, the Examiner contends that the limitations of the instant claims are taught by the references cited below, thus the claims are not in condition for allowance.
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.
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.
Claim(s) 1, 3, 5-10, 21, and 29-34 is/are rejected under 35 U.S.C. 103 as being unpatentable over O’Connor et al., (US 2016/0251441) in view of Goerke et al., (US 2014/0193876).
Regarding claims 1, 3, 10, 29-31, and 34 O’Connor et al., teach an elution buffer (paragraph 0087) comprising acetic acid (paragraph0087) and TCEP (paragraph 0087) wherein the elution buffer has a pH ranging from 2 to 5. The Examiner notes that the limitations regarding the target analytes, analyte specific antibodies, and mass spectrometry signals are not elements of the elution buffer, and therefore are given the appropriate patentable weight in the claims. O'Connor et al., do not teach the elution buffer comprising an ionization control protein or peptide.
Goerke et al., teach an elution buffer wherein the buffer comprises aprotinin (paragraph 0116). The Examiner notes that aprotinin is identical to the ionization control protein of the instant claims, thus the properties with respect to stability, and m/z peaks would be identical. Goerke et al., teach that it is advantageous to utilize aprotinin as a means of preventing proteolytic cleavage by host proteases (paragraph 0007).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify O'Connor et al., to include aprotinin in the elution buffer in order to prevent proteolytic cleavage by host proteases as taught by Goerke et al.
Regarding claim 5, O’Connor et al., do not teach an ionization control protein selected to have at least one mass spectrometry peak value within a m/z range required for detection of one or more peaks from the target analytes.
Goerke et al., teach an ionization control protein identical to that of the instant claims (aprotinin, paragraph 0116), thus the m/z peak would be identical to the m/z peak of the instant claims. Goerke et al., teach that it is advantageous to utilize aprotinin as a means of preventing proteolytic cleavage by host proteases (paragraph 0007).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify O'Connor et al., to include aprotinin in the elution buffer in order to prevent proteolytic cleavage by host proteases as taught by Goerke et al.
Regarding claims 6 and 7, O'Connor et al., in view of Goerke et al., teach a buffer comprising acetic acid and aprotinin, but do not explicitly teach 5% acetic acid and aprotinin in a range of 0.5 to 100 ng. The Examiner is reading these limitations as routine optimization which would have been obvious to one of ordinary skill in the art (MPEP 2144.05 II A). The MPEP states that differences in concentration will not support patentability of subject matter encompassed by the prior art absent evidence showing the concentration to be critical. The MPEP also states that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges (MPEP 2144.05 IIA). The Examiner has not found any evidence showing5% acetic acid and aprotinin ranging from 0.5 to 100 ng to be critical, thus the Examiner contends that one of ordinary skill would have found it obvious to utilize 5% acetic acid and aprotinin in a range of 0.5 to 100 ng as routine optimization requires only routine skill in the art.
Regarding claims 8 and 9, O’Connor et al., do not teach an ionization control comprising at least 30 amino acids, and having a mass of at least 3kDa.
Goerke et al., teach an ionization control protein identical to that of the instant claims (aprotinin, paragraph 0116), thus the number of amino acids and mass would also be identical. Goerke et al., teach that it is advantageous to utilize aprotinin as a means of preventing proteolytic cleavage by host proteases (paragraph 0007).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify O'Connor et al., to include aprotinin in the elution buffer in order to prevent proteolytic cleavage by host proteases as taught by Goerke et al.
Regarding claim 21, O’Connor et al., teach purifying a target antibody or desired fragment of a target antibody (paragraph 0047).
Regarding claim 32, the Examiner notes that the immunoglobulin or fragment thereof is not an element of the elution buffer, and therefore is not given patentable weight in the claim.
Regarding claim 33, O’Connor et al., do not teach a lock mass spectra calibrator.
Goerke et al., each a buffer comprising aprotinin (lock mass spectra calibrator, paragraph 0116). The Examiner notes that the instant specification states that the claimed ionization control can be used as the claimed lock mass spectra calibrator, thus any prior art teaching of aprotinin in an elution buffer also meets the limitation of the lock mass spectra calibrator. Goerke et al., teach that it is advantageous to utilize aprotinin as a means of preventing proteolytic cleavage by host proteases (paragraph 0007).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify O'Connor et al., to include aprotinin in the elution buffer in order to prevent proteolytic cleavage by host proteases as taught by Goerke et al.
Claim(s) 11, 14-19, and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over O'Connor et al., (US 2016/0251441) in view of Goerke et al., (US 2014/0193876) as applied to claim 1 above, and further in view of Witztum et al., (US 2015/0056209).
Regarding claims 11, 14, 19, and 22, O'Connor et al., in view of Goerke et al., teach immunoglobulins as an analyte (O'Connor et al., paragraph 0040) wherein diphtheria toxin is taught an analyte to be detected (Goerke et al., paragraph 0034), but do not teach a kit comprising an elution buffer and one or more analyte specific antibodies.
Witztum et al., teach a kit comprising an elution buffer(paragraph 0117), one or more antibodies (paragraphs 0074, 0075, 0112), and reagents for performing the assay (paragraph 0075). Witztum et al., also teach analyzing the analyte by MALDI-TOF mass spectrometry (paragraph 0073), The Examiner is reading this limitation as combining prior art elements according to known methods to yield predictable results which would have been obvious to one of ordinary skill in the art (MPEP 2141 III A). Reference to Witztum et al., teach that it is advantageous to utilize a kit as a means of providing reagents for preparing and detecting in a single package (paragraph 0075). Therefore, it would have been obvious to one of ordinary skill in the art to form the reagents in a kit as combining prior art elements according to known methods requires only routine skill in the art.
Regarding claim 15-18, O’Connor et al., in view of Goerke et al., do not teach anti-IgG antibodies.
Witztum et al., teach peptide mimotopes wherein IgG is taught as an analyte (paragraph 0082), and anti-IgG antibodies are utilized for detection (paragraph 0125). Witztum et al., also teach the kit comprising a control protein (paragraph 0117). The Examiner is reading this limitation as combining prior art elements according to known methods to yield predictable results which would have been obvious to one of ordinary skill in the art (MPEP 2141 III A). Reference to Witztum et al., clearly teach that anti-IgG antibodies can be utilized to detect IgG, thus one of ordinary skill in the art would have found it obvious to utilize anti-IgG antibodies to detect IgG. Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify O’Connor et al., in view of Goerke et al., wherein anti-IgG is utilized to detect IgG as combining prior art elements according to known methods to yield predictable results requires only routine skill in the art.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The Examiner makes note of reference to Fritz et al., (Drug Res. 33(1), Nr. 4 1983) cited in the Advisory Action dated March 4, 2026. As noted in the Advisory Action, reference to Fritz et al., teach that aprotinin can be exposed to solutions with pH values ranging from 1 to 12.6 with inactivation beginning at pH 12.8.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DWAN A GERIDO whose telephone number is (571)270-3714. The examiner can normally be reached Mon-Fri 10-6.
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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.
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/DWAN A GERIDO/Examiner, Art Unit 1797 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797
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