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 .
Claims 1, 2, 5, 8, 10, 17-22, 24, 26, 38, 39, 45-47 are pending in the application.
This office action is in response to the amendment filed on 1/21/2026.
All previous rejection not reiterated in this office action are withdrawn.
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 24, 38 and 47 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.
Regarding claim 24, the recitation of “selected from the group consisting of “blood, serum, plasma, cerebrospinal fluid, urine, tear, sputum, lavage fluid or saliva” renders the claim indefinite because the selection from alternatively recited members does not have multiple members to be selected from.
Regarding claim 38, the recitation of “wherein a neutralizing capacity of an immunoglobulin is determined by measuring molecules in the sample buffer indicative of neutralization of the bound antigen” renders the claim indefinite because it is unclear when this step is performed in the context of the claim steps from claim 1.
Regarding claim 47, the claim recites “the immune response” in line 6. There is insufficient antecedent basis for this limitation in the claim because claim 1 does not recite this limitation.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 5, 8, 10, 22 and 24 is/are rejected under 35 U.S.C. 102(a1) as being anticipated by Spencer (Blood, 11-13-2019, vol.134,supplemental 1, #651).
Spencer teaches a method of evaluating disease burden in multiple myeloma (MM) patients comprising: a) contacting a serum sample (which inherently comprises immunoglobulin) from MM patients with antibodies attached to paramagnetic microparticles; b) washing, elute and reduce immunoglobulins; c) subjecting the immunoglobulin to light chain mass spectra MALDI-TOF-MS (abstract, 2nd paragraph). Although polyclonal antibodies are attached to paramagnetic microparticles, such polyclonal antibodies binds the immunoglobulin in the serum sample. Since the specification does not provide a limiting definition for “antigen,” such “antibody” meets the limitation of “antigen” because they bind immunoglobulin in the sample specifically. Therefore, the teaching from spencer anticipates the method of claim 1.
Regarding claim 2, Spencer teaches the paramagnetic microparticles are attached with anti-IgG, IgA, IgM, total κ, total λ, free κ and free λ (2nd paragraph).
Regarding claim 5, Spencer teaches the immunoglobulin is reduced and separated light chain from heavy chain (2nd paragraph).
Regarding claim 8, Spencer teaches the immunoglobulin is quantitated (3rd paragraph).
Regarding claim 10, Spencer teaches the immunoglobulin classes are IgG, IgA, IgM) (2nd paragraph).
Regarding claim 22, Spencer teaches human patient (2nd paragraph).
Regarding claim 24, Spencer teaches the support is paramagnetic microparticles (2nd paragraph).
Response to Arguments
Applicant argues that Spencer describes using polyclonal antibodies targeting IgG, IgA, IgM, Kappa or lambda constant regions and Kappa and Lambda Free light chains, coupled to paramagnetic beads, followed by mass spectrometry.
This argument is not persuasive because the specification does not provide a limiting definition for structural and/or functional limitation for “antigen,” other than it binds the immunoglobulin in the sample. As such, the polyclonal antibodies taught by Spencer meets this claim limitation.
Applicant argues that Spencer does not teach identifying different antigen-specific immunoglobulin classes, but only polyclonal, non-specific IgG, IgA, IgM, Kappa or lambda antibodies, and captured immunoglobulins are polyclonal, so that they are not antigen specific immunoglobulins. Applicant argues that the class of a subject’s immunoglobulin is known before mass spectrometry, whereas the claimed method is used to determine antigen specific immunoglobulin classes and subclasses from spectral peaks.
This argument is not persuasive because binding of immunoglobulin to anti-IgG, IgA, IgM…etc is considered specific regardless of whether the antibody is polyclonal or monoclonal. There is no limitation in the rejected claims whether the antibody is monoclonal or polyclonal, nor does the claim recite any limitation whether the immunoglobulin in the sample is known or not. The amended claim 1 recites “a method of identifying or quantifying immunoglobulin classes and/or subclasses.” As such, since MS analysis taught by Spencer at least “quantifies” said immunoglobulin classes, the teaching anticipates the claimed invention because it discloses all method steps. Therefore, this rejection is still considered proper and thus maintained.
Claim(s) 1, 2, 5, 8, 10, 18-22, 24, 26, 39, 45-47 is/are rejected under 35 U.S.C. 102(a1) (a2) as being anticipated by Murray (WO2019/055632, IDS) as evidenced by Rodrigo (Antibodies 2015, Vol.4, pages 259-277). This is a new ground of rejection necessitated by amendment.
Murray teaches a method of identifying and quantifying immunoglobulin J chains in a sample using mass spectrometry (MS) techniques, and said method can be used to identify and quantify IgA immunoglobulins and IgM immunoglobulins (page 1, last paragraph). Murray teaches the biological sample may be biological fluids (page 9, line 31). Murray teaches immunoglobulins is isolated from the sample and enriched by removing contaminants from a sample by methods including affinity purification, using Protein A, Protein G, Protein L, wherein immunoglobulin are bound by those proteins at physiological pH and then released from the proteins by lowering pH (page 10, lines 15-18, 2-28). Murray teaches the affinity purification, the sample can be subject to a MS technique, wherein ion peaks can be examined to identify the J chains in the sample (page 13, lines 1-6 and 17-20). Although Murray does not specifically state that the protein A, protein G and protein L are attached to a solid support for affinity purification, it is well known in the art that such “antigen” is attaches to resin and commercially available as evidenced by the teaching from Rodrigo (Antibodies 2015, Vol.4, pages 259-277), (see page 266, lines 4-7).
Regarding claim 2, the teaching from Murray anticipates this claim because the separation step is optional.
Regarding claim 5, Murray teaches separating light chain and heavy chain prior to MS (page 12, lines 18-24).
Regarding claim 8, Murray teaches comparing the relative abundance of the J chain may be compared to reference and further determine multimeric IgA and IgM immunoglobulins for identifying patients with an IgA gammopathy and IgM gammopathy (page 14, lines 21-24).
Regarding claim 10, Murray teaches the immunoglobulin classes are IgA and IgM.
Regarding claim 18, it is known in the art that protein A is from Staphylococcus aureus, protein G is from streptococci, protein L is from Peptostreptococcus magnus (page 264, last paragraph, Rodrigo), which are bacteria.
Regarding claim 19 and 20, since claim 18 recites the antigen members in alternative, the teaching from Murray still meets all claim limitation.
Regarding claim 21, since protein A, G, and L are from bacterial cell, they meet the limitation of cellular antigen.
Regarding claim 22, Murray teaches that the sample can be from a patient that has immunoglobulin, including mammal, human, horse, sheep, cow or primate (page 9, lines 31-33).
Regarding claim 24, Murray teaches the sample includes blood, serum, plasma and saliva (page 9, lines 30-31).
Regarding claim 26, Murray teaches using ESI-Q-TOF MS to analyze MS of a sample (page 13, last paragraph). This type of analysis inherently requires an ionization control.
Regarding claim 39, the wherein clauses are not given patentable weight because it simply expresses the intended result but does not require active steps to be performed.
Regarding claim 45 and 46, Murray teaches immunoglobulin light chain types may be identified by methods disclosed in WO2015/154052), which teaches determining ratio of kappa and lambda immunoglobulin light chains in the sample after the step subjecting the sample to a mass spectrometry technique to obtain a mass spectrum of the sample (see ‘052 application IDS, page 3, lines 16-18).
Regarding claim 47, Murray teaches further determine multimeric IgA and IgM immunoglobulins for identifying patients with an IgA gammopathy and IgM gammopathy (page 14, lines 21-24).
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.
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Murray.
The teaching from Murray has been discussed above. However, Murray does not specifically teach which antigen specific immunoglobulin is eluted from the antigen first.
It would have been obvious to an ordinary skilled in the art that eluting an antigen from bound immunoglobulin may be eluted in multiple ways such as lowering pH and/or change the temperature etc as taught by Murray (page 10, line 28-29). Whether to elute the immunoglobulin with higher binding specificity or lower binding specificity first would have been a design choice depending on the type and condition of a specific immunoglobulin, which is not an inventive method. Therefore, the claimed invention of claim 17 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Conclusion
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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/CELINE X QIAN/ Primary Examiner, Art Unit 1637