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 .
Election/Restrictions
Applicant’s election of Group 1 (claims 1-7 and 9-10) in the reply filed on 6/15/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse. See MPEP § 818.01(a).
Claims 11-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Accordingly, claims 1-7 and 9-10 have been examined on the merits.
Priority
The instant application is a national stage entry of PCT/JP2022/017389 (filed on 4/08/2022), which claims priority benefit of U.S. Provisional Application No. 63/213852 (filed on 6/23/2021) under 35 U.S.C. 119(e).
Information Disclosure Statement
The four information disclosure statements (IDSs) submitted on 3/13/2024, 4/07/2025, 7/30/2025, and 7/17/2026 are in compliance with the provisions of 37 C.F.R. 1.97. All references cited in these IDSs have been fully considered.
Specification
The disclosure is objected to because of the following informalities: (i) the section title “REFERENCE SIGNS LIST” and paragraph [0131] should be deleted; and (ii) the reference characters listed in said paragraph should be described in the first line of par. [0011] as they are used in Figure 1.
Claim Objections
Claims 1 and 10 are objected to because of the following informalities: incomplete phrase. Applicant should add “step” after the phrase “obtained by the digesting” (line 4 of claim 1 and line 5 of claim 10) to resolve this issue.
Alternatively, applicant can delete said phrase and then insert the word “digested” before “biological protein” (line 3 of claim 1 and line 4 of claim 10) as well as before “target antibody/antibodies” (line 4 of claim 1 and line 5 of claim 10).
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.
Claims 1-7 and 9-10 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1 and 10 require the step of “quantifying the target antibody based on a ratio between a detected intensity of the biological protein and a detected intensity of the target antibody obtained by the mass spectrometry”. Given the use of the term “between” in said step (instead of “to” after “intensity of the biological protein”, which would have established the order of the variables), it cannot be determined if the ratio is calculated by dividing the biological protein’s intensity by the target antibody’s intensity, or the other way around. For the purpose of applying prior art, the first interpretation is taken by the examiner.
Claim 2 recites two additional steps but it is unclear when they should be performed in the process set forth in claim 1 (ex. before or after digesting?). Does it matter when these two additional steps are conducted? In the interest of compact prosecution, claim 2 is interpreted to mean the two additional steps being carried out prior to the digesting step.
Claims 3-7 and 9 are also considered indefinite for depending on claim 1.
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.
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 1-5, 7 and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Iwamoto et al. (Pub. No. US 2020/0011876 A1) in view of Lebert et al. (Pub. No. US 2019/0085056 A1).
Iwamoto et al. discloses a method of simultaneous analysis of antibody drugs (Abstract). The method involves: (i) adding a porous body having pores in which monoclonal antibodies are immobilized in a liquid containing nanoparticles on which proteases are immobilized; and (ii) selectively proteolyzing the monoclonal antibodies to detect peptide fragments each comprising unique amino acid sequence derived from the Fab region of the monoclonal antibodies through liquid chromatography-mass spectrometry (LC-MS), wherein peptide fragments of two or more types of monoclonal antibodies in the same biological sample are simultaneously quantified (par. [0022]).The biological sample is derived from blood or tissue of a patient to which monoclonal antibodies has been administered in the form of antibody drugs (par. [0039]). Moreover, a complex having an additional function while maintaining specificity of a monoclonal antibody, such as an Fc fusion protein can also be included in monoclonal antibodies to be measured (par. [0067]).
Iwamoto et al. also discloses a composition containing two or more types of peptide fragments, each of which comprises an amino acid sequence derived from the Fab region of a monoclonal antibody produced by selective proteolysis. This composition can be used as a standard for simultaneous quantification of different types of monoclonal antibodies (par. [0043]).
The method of Iwamoto et al. is comparable to the instant application’s antibody analysis method for the following reasons:
Regarding claims 1 and 9-10: selectively proteolyzing two or more monoclonal antibodies immobilized in the pores of the porous body is the same as “digesting a biological protein and a target antibody with a protease” and satisfies “wherein the target antibody includes at least two antibodies”.
The monoclonal antibodies being immobilized inside the pores of the porous body (par. [0069]-[0072]) is analogous to “the digesting with a protease including: immobilizing the biological protein and the target antibody inside pores of a support”.
Adding the monoclonal antibody-containing porous body in a liquid containing nanoparticles with immobilized proteases corresponds to “bringing a microparticle close to the support”.
The nanoparticles having an average particle size larger than the average pore size of the porous body (par. [0077]-[0080]) fulfills “the microparticle having a diameter larger than a diameter of the pores and having a surface to which a protease is immobilized”.
The nanoparticles having spacer molecules capable of binding and immobilizing proteases (par. [0081]-[00821]) satisfies “having a surface to which a protease is immobilized”.
Analyzing and determining concentration of peptide fragments from the monoclonal antibodies in a sample via LC-MS (par. [0100]-[0103]) is comparable to “quantifying the target antibody based on a ratio between a detected intensity of the biological protein and a detected intensity of the target antibody obtained by the mass spectrometry”.
Iwamoto et al. differs from the claimed invention in that it does not specifically teach determining the recited ratio.
Nonetheless, Lebert et al. teaches methods of quantifying antibodies that are compatible with proteolysis before MS to allow multiplex quantification (par. [0020]-[0021]). Lebert et al. teaches using mass spectrometric analysis to determine the ratio between (i) one or more selected proteolysis labeled peptides from a labeled antibody-like protein and (ii) one or more corresponding proteolysis peptides derived from one or more therapeutic antibodies in a sample of an individual, followed by calculating the amount of the one or more antibodies from the determined ratio (par. [0034]-[0038]).
A person with ordinary skill in the art before the effective filing date of the claimed invention would have applied the teachings of Lebert et al. to Iwamoto et al.’s method with reasonable expectation that it would allow the amount of a monoclonal antibody in a sample to be calculated or measured. The rationale to support obviousness is that all claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. See MPEP § 2143 and KSR, 550 U.S. 398, 82 USPQ2d at 1395; Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976).
Hence, the claims are obvious over Iwamoto et al. in view of Lebert et al..
Regarding claim 2: Iwamoto et al.’s teaching of using an antibody as internal standard for quantifying antibodies by MS (par. [0028]), which is considered to read on the limitations of the instant claim.
Regarding claim 3: the monoclonal antibodies including complexes like an Fc fusion protein (par. [0065]-[[0067]) meets “wherein the biological protein includes a reference antibody or an Fc fusion protein”.
Regarding claim 4: the monoclonal antibodies are the same as “wherein the reference antibody is a monoclonal antibody”.
Regarding claim 5: applicable monoclonal antibodies include trastuzumab, bevacizumab, cetuximab, rituximab, nivolumab, brentuximab, ipilimumab, mogamulizumab, ramucirumab, infliximab, tocilizumab, adalimumab, golimumab, mepolizumab, and eculizumab (par. [0027], [0066]), thereby meeting the limitation “wherein the reference antibody is selected from the group consisting of trastuzumab. bevacizumiab. cetuximab.ituximab, nivolumab, brentuximab, pembrolizumab, ipilimumab, mogamulizumab, ramucirumab, atezolizumab,durvalumab, avelunab, infliximab, tocilizunab. adalimumab.golintumab, mepolizumab, ustekinumab, and eculizumab”.
Regarding claim 7: the monoclonal antibodies being present in a biological sample of a patient to which monoclonal antibodies has been administered in the form of antibody drugs (par. [0039], [0125]) is equivalent to “wherein the target antibody is an antibody contained in a biological sample”.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE F PAGUIO FRISING whose telephone number is (571)272-6224. The examiner can normally be reached Monday-Friday, 8:00 a.m. - 4:00 p.m..
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie L. 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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/Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651
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