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
Claims 1-4, 8, 10 and 12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/09/2026.
Applicant’s election without traverse of Group II, claims 19, 20, 22, 27-29, 32, 36, 39, 44, 45 and 54 in the reply filed on 02/09/2026 is acknowledged.
Claim Rejections - 35 USC § 102
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.
Claim(s) 19, 20, 22, 27, 29 and 54 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Adamcyzk et al (US PGPub 2009/0286329), cited on the IDS.
Regarding Claim 19, Adamcyzk et al discloses a method for obtaining a plurality of enriched peptides or polypeptides in a sample (the present disclosure relates to an isolated human natriuretic peptide autoantibody that is obtained by a process, see [0072]), comprising the steps of (a) Contacting the sample with beads comprised of a single type of bead (such as polystyrene beads) (see [0028], [0234] and [0304]);
b) Separating a portion of the sample comprising protein-bound beads from a portion of the sample comprising unbound proteins (i.e. removing any unbound one or more autoantibodies from the bead complex, see [0031], or magnetically sequestering of the bulk microparticles, see [0329] ) ; and
(c) Resuspending the portion of the sample comprising protein-bound beads, thereby obtaining a plurality of enriched peptides or polypeptides in the sample (see [0329]-[0330] and [0337]).
Regarding Claim 20, Adamcyzk et al teaches that the sample is a physiological fluid, including, but not limited to, whole blood, serum, plasma, interstitial fluid, saliva, ocular lens fluid, cerebral spinal fluid, sweat, urine, milk, ascites fluid, mucous, nasal fluid, sputum, synovial fluid, peritoneal fluid, vaginal fluid, menses, amniotic fluid, semen and so forth (see [0212]).
Regarding Claim 22, Adamcyzk et al teaches that the beads are magnetic (see [0234] and [0330]).
Regarding Claim 27, Adamcyzk et al teaches that the method is performed at a temperature of about 37 degrees Celsius (see [0314], [0323] and [0344]).
Regarding Claim 29, Adamcyzk et al teaches that the method of separating of step b) comprises magnetic immobilization to separate a portion of protein- bound beads from a portion of unbound plasma proteins and unbound beads in the sample (see [0304] and [0329]-[0330]).
Regarding Claim 54, Adamcyzk et al teaches a method for quantifying or identifying peptides or polypeptides in a sample, comprising the steps of:(a) Obtaining a plurality of enriched peptides or polypeptides according to the method of claim 19 (as described in claim 19 rejection); and analyzing the peptides and polypeptides so as to obtain mass spectrometry data; thereby quantifying or identifying peptides or polypeptides in a sample (see [0233], [0253] and [0286]).
Claim(s) 19, 20, 22, 27-28, 31 and 54 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Patel et al (WO 2019168843), as cited on the IDS.
Regarding Claim 19, Patel et al discloses a method for obtaining a plurality of enriched peptides or polypeptides in a sample (see abstract), comprising the steps of (a) Contacting the sample with beads comprised of a single type of bead (see [0052] and [0077]);
b) Separating a portion of the sample comprising protein-bound beads from a portion of the sample comprising unbound proteins (wherein “a sample that has been enriched (including immunoaffmity enrichment) for one or more target proteins may be subjected to an elution step to separate the antibody-protein complex from a solid support. In embodiments, the elution may be an enzymatic elution. In embodiments, an elution may be performed with a low pH/organic reagent. In embodiments, an enriched sample (including an immunoaffmity-enriched sample) may first be subjected to an enzymatic elution”, see [0053]); In addition, Patel et al teaches that the protein samples are separated using liquid chromatography (see [0069]).
In addition, Patel et al teaches that the method further includes (c) Resuspending the portion of the sample comprising protein-bound beads, thereby obtaining a plurality of enriched peptides or polypeptides in the sample ( see [0080] and [0083]).
Regarding Claim 20, Patel et al teaches that the sample may be isolated cells, plasma, serum, whole blood, CSF, urine, sputum, tissue, and tumorous tissue (see [0014]).
Regarding Claim 22, Patel et al teaches that the beads are magnetic (see [0052] and [0063]).
Regarding Claim 27, Patel et al teaches that the method is performed at a temperature of about 37 degrees Celsius (see [0079]).
Regarding Claim 28, Patel et al teaches that the plurality of enriched peptides or polypeptides comprises one or more protein complexes and the method further comprises reducing the plurality of enriched peptides or polypeptides (see [0051], [0053]-[0054] and [0056]).
Regarding Claim 31, Patel et al teaches that the method further comprises alkylating the plurality of enriched peptides or polypeptides (see [0051] and [0056]).
Regarding Claim 54, Patel et al teaches a method for quantifying or identifying peptides or polypeptides in a sample, comprising the steps of:(a) Obtaining a plurality of enriched peptides or polypeptides according to the method of claim 19 (as described in claim 19 rejection); and analyzing the peptides and polypeptides so as to obtain mass spectrometry data; thereby quantifying or identifying peptides or polypeptides in a sample (see [0045]-[0046] and [0067]-[0068]).
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.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Patel et al (or Adamcyzk et al) as applied to claim 19 above, and further in view of Wilcox et al (US PGPub 2021/0063410). Regarding Claim 32, both Adamczyk et al and Patel et al teach the method of claim 19.
However, neither Patel et al nor Adamcyzk et al teaches performing the method on an automated liquid handling robot.
However, in the analogous art of method and systems for mass spectrometric analysis of biological samples, Wilcox et al teaches that the systems can be automated, for example by connecting at least some of the individual modules to one another such that the samples produced or manipulated by a module are automatically fed to a subsequent module in a particular work flow. This is done through any number of automated approaches, such as using sample handling robots or by connecting the fluidics between modules. As another example, the system can be automated by connecting at least one of the individual sample handling modules to a module comprising a detector that evaluates the quality of the output of the previous step in a particular work flow and flags or gates a sample based on the results of that analysis (see [0088]). It would have been obvious to one of ordinary skill in the art to perform the method of claim 19 with an automated robot (as taught by Wilcox et al) for the benefit of enabling automated movement between each step of claim 19 and such that sample volume may be volumetrically dispensed between modules through use of the robot.
Claims 36, 39, 44 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Patel et al (or Adamcyzk et al) as applied to claim 19 above, and further in view of Schulzknappe et al (US PGPub 2015/0241443).
Regarding Claim 36, neither Patel et al (or Adamcyzk et al) teaches that the method further comprises isobarically labellling the plurality of enriched peptides or polypeptides.
However, in the analogous art of methods for assaying analytes, Schulzknappe et al teaches that the mass labels used in the method further comprise an affinity capture ligand. The affinity capture ligand of the mass label binds to a counter-ligand so as to separate the isobarically labeled analytes from the unlabelled analytes after step (a) but before step (b). The affinity capture ligand provides a means of enrichment of the analytes of interest, thereby increasing analytical sensitivity (see [0043]). Furthermore, Schulzknappe et al teaches that the affinity capture ligand of the mass label binds to a counter-ligand so as to separate the isobarically labeled analytes from the unlabelled analytes after step (a) but before step (b) (see [0176]). It would have been obvious to one of ordinary skill in the art to isobarically label the enriched peptides/polypeptides (as taught by Schulzknappe et al) for the benefit of providing a means of enrichment of the analytes of interest, thereby increasing analytical sensitivity.
Regarding Claim 39, the combination of Adamcyzk et al (or Patel et al) and Schulzknappe et al teaches:
Obtaining a plurality of labeled peptides or polypeptides according to the method of claim 36 ( see the claim 36 rejection);
Aliquoting the labeled peptides into two or more portions (after a first separation was performed, see [0235] of Schulzknappe et al);
Combining the two or more isotopically labeled peptides or polypeptides into one plex (After labeling the aliquots were mixed volumetrically, see [0234] of Schulzknappe et al);
Splitting the plex of labeled peptides or polypeptides into two or more portions for clean-up (The second separation system was a reversed phase chromatography, see [0236] of Schulzknappe et al);
Re-combining the portions into one plex (After labeling the aliquots were mixed volumetrically, see [0234]); and analyzing the labeled peptides or polypeptides so as to obtain mass spectrometry data (To determine the proteome coverage of the reference
material it was subjected to multi-dimensional chromatography and tandem mass spectrometry analysis, see [0234] of Schulzknappe et al); thereby quantifying
and identifying identifying two or more chemically isotopic labeled peptides or polypeptides (the analyte in the sample and in the calibration sample can be simultaneously quantified and identified by tandem mass spectrometry)(see [0034] of Schulzknappe et al.).
Schulzknappe et al does not disclose clean-up of each portion, however Adamcyzk et al teaches cleaning (washing) up each portion (see [0246], [0307] and [0330]) and Patel et al also teaches cleaning (washing) up each portion (see [0077] and [0121]). It would have been obvious to one of ordinary skill in the art to clean-up each portion for the benefit of efficiently removing antibodies from the bead complex.
Regarding Claim 44, Schulzknappe et al teaches a method for quantifying or identifying peptides or polypeptides in a sample comprising:
Incorporating isotopic labels onto each peptide or polypeptide in the portion of the sample comprising protein-bound beads (see [0017] and [0202]);
Aliquoting the labeled peptides into two or more portions (after a first separation was performed, see [0235]);
Combining the two or more isotopically labeled peptides or polypeptides into one plex (After labeling the aliquots were mixed volumetrically, see [0234]);
Splitting the plex of labeled peptides or polypeptides into two or more portions for clean-up (The second separation system was a reversed phase chromatography, see [0236]l);
Re-combining the portions into one plex (After labeling the aliquots were mixed volumetrically, see [0234]); and analyzing the labeled peptides or polypeptides so as to obtain mass spectrometry data (To determine the proteome coverage of the reference material it was subjected to multi-dimensional chromatography and tandem mass spectrometry analysis, see [0234]); thereby quantifying and identifying identifying two or more chemically isotopic labeled peptides or polypeptides (the analyte in the sample and in the calibration sample can be simultaneously quantified and identified by tandem mass spectrometry)(see [0034])
Schulzknappe et al does not disclose obtaining the plurality of enriched peptides or polypeptides of claim 19.
However, Adamcyzk et al discloses a method for obtaining a plurality of enriched peptides or polypeptides in a sample (the present disclosure relates to an isolated human natriuretic peptide autoantibody that is obtained by a process, see [0072]), comprising the steps of (a) Contacting the sample with beads comprised of a single type of bead (such as polystyrene beads) (see [0028], [0234] and [0304]); b) Separating a portion of the sample comprising protein-bound beads from a portion of the sample comprising unbound proteins (i.e. removing any unbound one or more autoantibodies from the bead complex, see [0031], or magnetically sequestering of the bulk microparticles, see [0329] ) ; and (c) Resuspending the portion of the sample comprising protein-bound beads, thereby obtaining a plurality of enriched peptides or polypeptides in the sample (see [0329]-[0330] and [0337]).
In addition, Patel et al teaches a) Contacting the sample with beads comprised of a single type of bead (see [0052] and [0077]); b) Separating a portion of the sample comprising protein-bound beads from a portion of the sample comprising unbound proteins (wherein “a sample that has been enriched (including immunoaffmity enrichment) for one or more target proteins may be subjected to an elution step to separate the antibody-protein complex from a solid support. In embodiments, the elution may be an enzymatic elution. In embodiments, an elution may be performed with a low pH/organic reagent. In embodiments, an enriched sample (including an immunoaffmity-enriched sample) may first be subjected to an enzymatic elution”, see [0053]); In addition, Patel et al teaches that the protein samples are separated using liquid chromatography (see [0069]).
In addition, Patel et al teaches that the method further includes (c) Resuspending the portion of the sample comprising protein-bound beads, thereby obtaining a plurality of enriched peptides or polypeptides in the sample ( see [0080] and [0083]).
Therefore it would have been obvious to one of ordinary skill in the art to Obtaining the plurality of enriched peptides or polypeptides of claim 19 (which involves resuspension) for the benefit of enabling the protein to be resuspended in the needed fluid.
Regarding Claim 45, the combination of Adamcyzk et al (or Patel et al) does not teach that the method further comprises mixing the two or more peptides or polypeptides prior to the splitting in step (g) .
However, in the analogous art of methods for assaying analytes, Schulzknappe et al teaches that plasma was labeled and mixed to create a whole plasma proteome calibration mixture preparation of a human reference plasma was performed and the plasma was spiked with two proteins (see [0230]-[0231] of Schulzknappe et al). It would have been obvious to one ordinary skill in the art to mix the two peptides for the benefit of forming a whole plasma proteome calibration mixture that may be utilized as reference material.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 19, 20, 22, 27-29, 31, 32, 36, 44, 45 and 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims ??? of copending Application No. 18/981,314 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following:
Regarding Claim 19, claim 21 of reference application ‘314 discloses identical subject matter.
Regarding Claim 20, claim 22 of reference application ‘314 discloses identical subject matter.
Regarding Claim 22, claim 24 of reference application ‘314 discloses identical subject matter.
Regarding Claim 27, claim 29 of reference application ‘314 discloses identical subject matter.
Regarding Claim 28, claim 30 of reference application ‘314 discloses identical subject matter.
Regarding Claim 29, claim 31 of reference application ‘314 discloses identical subject matter.
Regarding Claim 31, claim 33 of reference application ‘314 discloses identical subject matter.
Regarding Claim 32, claim 34 of reference application ‘314 discloses identical subject matter.
Regarding Claim 36, claim 38 of reference application ‘314 discloses identical subject matter.
Regarding Claim 39, claim 41 of reference application ‘314 discloses identical subject matter.
Regarding Claim 44, claim 47 of reference application ‘314 discloses identical subject matter.
Regarding Claim 45, claim 49 of reference application ‘314 discloses identical subject matter.
Regarding Claim 54, claim 58 of reference application ‘314 discloses identical subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Lund-Johansen et al (US PGPub 20200018763 A1) discloses methods for assessing binding agent specificity, in particular antibody specificity. The present invention thus provides a method of analysing a mixture of polypeptides comprising the steps of: (i) separating the polypeptides in the mixture into a plurality of fractions; (ii) contacting a first aliquot of two or more of the fractions with a plurality of different binding agents attached to one or more solid supports and detecting the binding of the polypeptides to the binding agents in each fraction; (iii) assessing the amino acid composition of the polypeptides in a second aliquot of said fractions by mass spectrometry; and (iv) correlating the binding results detected in step (ii) and the mass spectrometry results from step (iii) to assess the specificity of the binding agents for a polypeptide of interest (see abstract). In addition, Lund-Johansen et al teaches that the method further comprises resuspending the protein-bound beads (see [0296] and [0315]).
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/JENNIFER WECKER/ Primary Examiner, Art Unit 1797