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 .
The response dated 3/16/2026 is acknowledged. Claims 1-23 and 34-39 are pending. Claims 24-33 are cancelled. Claims 34-39 are new. Claims 1-23 and 34-39 are considered on the merits below.
Response to Amendment
Applicant's amendments, filed 3/16/2026, with respect to the objection to the specification have been fully satisfied and withdrawn.
In response to the applicant's amendments, the grounds of rejection for claims 1-23 and 34-39 are new compared to the previous action, however rely on the same prior art.
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 1-23 and 34-39 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 2A, Prong 1: identify the abstract ideas. Regarding claims 1, 11, and 35, the claims have the abstract idea of “comparing”. This “comparing” is an evaluation which is a mental process and abstract idea.
Step 2A, Prong 2: has the abstract ideas been integrated into a particular practical application? Once the abstract idea/comparing is completed, the next step is
manufacturing a protein. However, there are no actual manufacturing steps. As such, it appears there is not a tangible application, and by extension, no practical application either.
Step 2B: does the claim recite any elements which are significantly more than the abstract idea? Claimed elements other than the abstract idea include obtaining samples, preparing the samples for NMR, obtaining an NMR spectra, and averaging (claims 1 and 37) or doing a principal component analysis (claim 11) on the NMR spectra. These are all well-known routine and conventional in the art, and thus not “significantly more”.
Dependent claims only further refine the abstract idea.
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.
Claim(s) 1-3, 6-8, 10-16, 23 and 34-39 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tsao et al. (US 2019/0079100 A1).
Regarding claim 1, Tsao describes a method for manufacturing at least one protein ([0036] “evaluation (comparison) of different manufacturing” ), comprising:
a. obtaining a plurality of samples from each of at least two manufacturing processes ([0035] “a glycoprotein preparation (e.g., such as a glycoprotein drug substance or a precursor thereof) can be a sample from a proposed or test batch of a drug substance or drug product.”);
b. preparing said samples for NMR spectroscopy ([0099] “Samples of an intact target antibody, an intact test antibody (having the same amino acid sequence as the target antibody), and two additional intact antibodies ("non-target antibody 1" and "non-target antibody 2", each of which had amino acid sequences that differed from the target antibody) were buffer exchanged into a formulation buffer containing 7.34 mM Citrate, pH=5.2, 104 mM NaCl in 100% D20, at a concentration of 45-50 mg/mL. NMR samples were prepared in a regular NMR tube”);
c. subjecting prepared samples to a NMR experiment ([0099] “HMQC NMR acquisition time was around 2.5 days, with 2048x400 points acquired and 512 scans each point. Data was processed in Topspin software”);
d. obtaining NMR spectra for said samples from said NMR experiment ([0101] “The 2D HMQC spectrum of glycosylated target antibody (where glycans were cleaved from the target antibody), showing methyl peaks, is depicted in FIG. 1. The overlays of 2D HMQC NMR spectra of the target antibody with the test antibody are shown in FIG. 2 (which shows methyl peaks). Spectral similarities were observed for methyl peaks in the target antibody and the test antibody, as shown in FIG. 2. Overlays of 2D HMQC NMR spectra of the target antibody with non-target antibody 1 is shown in FIG. 3; and spectra of the target antibody with non-target antibody 2 is shown in FIG. 4 (all figures depicting methyl peaks), where the differences are highlighted.”);
e. averaging said spectra of each plurality of sample from said at least two manufacturing processes (“Example 3: Characterization of Antibodies by Comparison of Point Intensities” and [0127] “For all samples, point intensities were evaluated from 6.49 ppm to 12.00 ppm, using 2259 points. To decrease the number of points for comparison, point intensities were binned by averaging the intensity for every 10 points.”);
f. comparing said averaged NMR spectra from said at least two manufacturing processes to detect differences in protein higher order structure ([0127] “Comparison between two samples was made by plotting a correlation plot, where all the points/intensities for both samples are plotted and the correlation of fit is calculated.” And [0115] “This demonstrates that differences in relative peak intensity can be used to assess similarity of higher-order structure of proteins.”).
g. selecting a favored manufacturing process based on the comparison; and h. subsequently manufacturing at least one protein according to the favored manufacturing process ([0079] Methods described herein may include making a decision: (a) as to whether a protein preparation may be formulated into drug substance or drug product; (b) as to whether a protein preparation may be reprocessed ( e.g., the preparation may undergo a repetition of a previous process step);).
Regarding claims 2 and 3, Tsao describes the method of claim 1, wherein said protein is an antibody, a bispecific antibody, a multispecific antibody, antibody fragment, monoclonal antibody, antibody drug conjugate, antibody/targeted drug conjugate, conjugated monoclonal antibody, conjugated monoclonal antibody fragment, or an Fc fusion protein ([0034] “antibodies include monoclonal antibodies”).
Regarding claim 6, Tsao describes the method of claim 1, wherein said NMR spectra are 2D-NMR spectra ([0068] “two-dimensional NMR (2D-NMR)”).
Regarding claim 7, Tsao describes the method of claim 6, wherein said 2D-NMR spectra are obtained using a homonuclear NMR experiment through correlation spectroscopy (COSY), total correlation spectroscopy (TOCSY) or nuclear Overhauser effect spectroscopy (NOESY) ([0068] “correlation spectroscopy magnetic-angle spinning NMR (COSY-NMR”).
Regarding claim 8, Tsao describes the method of claim 6, wherein said 2D-NMR spectra are obtained using a heteronuclear NMR experiment through 1H-15N HSQC or 1H-13C HSQC ([0068] “heteronuclear single-quantum coherence NMR (HSQC-NMR),” and [0027] “2D 1H-13C correlation spectrum”).
Regarding claim 10, Tsao describes the method of claim 1 capable of comparing two manufacturing processes of protein ([0036] “evaluation (comparison) of different manufacturing”).
Regarding claim 11, Tsao describes a method of manufacturing at least one protein ([0036] “evaluation (comparison) of different manufacturing”), comprising:
(a) obtaining a plurality of protein samples from each of at least two manufacturing processes ([0035] “a glycoprotein preparation (e.g., such as a glycoprotein drug substance or a precursor thereof) can be a sample from a proposed or test batch of a drug substance or drug product.”);
(b) preparing said samples for NMR spectroscopy ([0099] “Samples of an intact target antibody, an intact test antibody (having the same amino acid sequence as the target antibody), and two additional intact antibodies ("non-target antibody 1" and "non-target antibody 2", each of which had amino acid sequences that differed from the target antibody) were buffer exchanged into a formulation buffer containing 7.34 mM Citrate, pH=5.2, 104 mM NaCl in 100% D20, at a concentration of 45-50 mg/mL. NMR samples were prepared in a regular NMR tube”);
(c) subjecting said samples to a NMR experiment ([0099] “HMQC NMR acquisition time was around 2.5 days, with 2048x400 points acquired and 512 scans each point. Data was processed in Topspin software”);
(d) subjecting resulting NMR spectra to a principal component analysis to compare manufacturing processes to detect differences in protein higher order structure ([0028] “In some embodiments, the step of comparing comprises a statistical analysis ( e.g., linear regression analysis) and the representation is a linear regression plot” and “Analysis Methods” and [0067] “analyze signals associated with higher-order structure of a protein,” Examiner’s note: “principal component analysis” is a technique used to reduce the dimensionality of large datasets by transforming the data onto a new, lower-dimensional coordinate system which is being done in the cited portions.).
(e) selecting a favored manufacturing process based on the comparison; and (f) subsequently manufacturing at least one protein according to the favored manufacturing process ([0079] Methods described herein may include making a decision: (a) as to whether a protein preparation may be formulated into drug substance or drug product; (b) as to whether a protein preparation may be reprocessed ( e.g., the preparation may undergo a repetition of a previous process step);).
Regarding claim 12, Tsao describes The method of claim 11, wherein said NMR spectra in said principal component analysis are clustered by manufacturing process (“Example 4: Manufacture of a Biosimilar Protein” [0137] “Samples of an intact test protein are obtained, which protein is in a first state. A sample of the test protein in the first state is exposed to a stressor to obtain a sample of the test protein in a second state. NMR is used to detect representative peaks for the protein in the first state and corresponding peaks for the protein in the second state. Differences in relative peak intensities are determined between the representative peaks for the protein in the first state and corresponding peaks for the protein in the second state to determine a test protein delta. Linear regression analysis is used to compare the test protein delta to a corresponding target protein delta of a target protein to produce a linear regression plot. The target protein has an amino acid sequence at least 98% identical to the test protein. An R2 value of 0.91 is determined for the linear regression plot, which is tolerable. The test protein is processed into drug product for administration.”).
Regarding claim 13, Tsao describes the method of claim 12, further comprising subjecting said principal component analysis clusters to statistical analysis to compare manufacturing processes (“Example 4: Manufacture of a Biosimilar Protein” [0137] “Samples of an intact test protein are obtained, which protein is in a first state. A sample of the test protein in the first state is exposed to a stressor to obtain a sample of the test protein in a second state. NMR is used to detect representative peaks for the protein in the first state and corresponding peaks for the protein in the second state. Differences in relative peak intensities are determined between the representative peaks for the protein in the first state and corresponding peaks for the protein in the second state to determine a test protein delta. Linear regression analysis is used to compare the test protein delta to a corresponding target protein delta of a target protein to produce a linear regression plot. The target protein has an amino acid sequence at least 98% identical to the test protein. An R2 value of 0.91 is determined for the linear regression plot, which is tolerable. The test protein is processed into drug product for administration.”.
Regarding claim 14, Tsao describes the method of claim 11, further comprising determining at least one area of said NMR spectra that contributes to at least one difference measured using principal component analysis, wherein said area is determined by plotting at least one loading as a contour plot on said NMR spectra (figures 1-4 and [0047] “A "signal integral", as used herein, refers to magnitude of a particular signal. In some embodiments, a signal integral is obtained by measuring signal area and/or signal volume, e.g., in an NMR spectrum.”).
Regarding claims 15 and 16, Tsao describes the method of claim 11, wherein said protein is an antibody, a bispecific antibody, a multispecific antibody, antibody fragment, monoclonal antibody, or an Fc fusion protein ([0034] “antibodies include monoclonal antibodies”).
Regarding claim 23, Tsao describes the method of claim 11 capable of comparing two manufacturing processes of protein ([0036] “evaluation (comparison) of different manufacturing”).
Regarding claim 34, Tsao describes the method of claim 1, further comprising eliminating noise from empty areas of the obtained NMR spectra prior to averaging ([0048] “A "signal associated with higher-order structure", as used herein, refers to a collection of one or more signals obtained for a protein wherein a signal is associated with an NMR peak with a signal to noise ratio of greater than 3, for example, greater than 4, 5, 6, 7, 8, 9, 10. In some embodiments, a signal associated with higher-order structure of a protein includes signals associated with about 1-40 ( e.g., about 1-30, e.g., 1-20, e.g., 1-10) of representative peaks of an NMR spectrum.).
Regarding claim 35, Tsao describes the method of claim 34, wherein eliminating noise comprises:(i) dividing the NMR spectrum into bins;(ii) selecting an empty area of the NMR spectrum;(iii) setting a noise threshold based on the signal intensity in the empty area; and(iv) adjusting the NMR spectrum signal such that all bins with signal intensity below the noise threshold are set to an adjusted signal intensity of zero ([0028] In some embodiments, the step of comparing comprises a statistical analysis ( e.g., linear regression analysis) and the representation is a linear regression plot. In some embodiments, the representation is tolerable if it meets a threshold or predetermined value. In some embodiments, a threshold or predetermined value is an R2 value of at least 0.8, 0.85, 0.9, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, 0.98, 0.99, or 1.”).
Regarding claim 36, Tsao describes the method of claim 35, further comprising excluding bins with an adjusted signal intensity of zero from analysis [0028] In some embodiments, the step of comparing comprises a statistical analysis ( e.g., linear regression analysis) and the representation is a linear regression plot. In some embodiments, the representation is tolerable if it meets a threshold or predetermined value. In some embodiments, a threshold or predetermined value is an R2 value of at least 0.8, 0.85, 0.9, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, 0.98, 0.99, or 1.”)..
Regarding claim 37, Tsao describes method for manufacturing a protein, comprising:
manufacturing a protein according to a favored manufacturing process ([0079] “Methods described herein may include making a decision: (a) as to whether a protein preparation may be formulated into drug substance or drug product; (b) as to whether a protein preparation may be reprocessed ( e.g., the preparation may undergo a repetition of a previous process step);”);
wherein the favored manufacturing process is based on a comparison of a first averaged NMR spectrum to a second averaged NMR spectrum that detects differences in protein higher order structure between the protein manufactured by a first process and the protein manufactured by a second process (claim 48 “comparing one or more cross-peaks in the first 2D NMR spectrum with one or more corresponding cross-peaks in the second 2D NMR spectrum to produce a representation; and processing the preparation of the test glycoprotein drug substance as drug product if the representation is tolerable; or taking alternative action if the representation is not tolerable.”).
Regarding claim 38, Tsao describes the method of claim 37, wherein, prior to the comparison, carrying out site- specific hydrolysis of a first plurality of samples of the protein obtained from the first process and carrying out site-specific hydrolysis of a second plurality of samples of the protein obtained from the second process; obtaining NMR spectra of the samples; eliminating noise from empty areas of the obtained NMR spectra; normalizing signal intensities in each of the spectra to obtain normalized spectra; averaging the normalized spectra of the first plurality of samples to obtain the first averaged NMR spectrum; and averaging the normalized spectra of the second plurality of samples to obtain the second averaged NMR spectrum ([0049] “Exemplary stressors capable of inducing a change in NMR response include, without limitation, NMR shift reagents ( e.g., one or more of deuterium or 4-hydroxy-2,2,6,6-tetramethyl-piperidine-l-oxyl (TEMPOL)).” and [0091] “In addition, a host cell strain can be chosen that modulates expression of inserted sequences, or modifies and processes the gene product in the specific fashion desired.”).
Regarding claim 39, Tsao describes the method of claim 37, wherein the first plurality of samples includes samples selected from a plurality of manufacturing lots manufactured by the first process; and/or wherein the second plurality of samples includes samples selected from a plurality of manufacturing lots manufactured by the second process ([0079] “Methods described herein may include making a decision: (a) as to whether a protein preparation may be formulated into drug substance or drug product; (b) as to whether a protein preparation may be reprocessed ( e.g., the preparation may undergo a repetition of a previous process step); and/or (c) that the protein preparation is not suitable for formulation into drug substance or drug product. In some instances, methods comprise: formulating as referred to in step (a), reprocessing as referred to in step (b), or rendering the preparation unusable for commercial release, e.g., by labeling it or destroying it, as referred to in step (c).”).
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.
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) 4, 5, and 17-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsao et al. (US 2019/0079100 A1) in view of Switzar et al. (J. Proteome Res. 2013, 12, 1067−1077).
Regarding claims 4 and 5, Tsao describes the method of claim 1, however is silent to wherein preparing said samples for NMR spectroscopy includes a step of contacting said samples to at least one hydrolyzing agent or wherein said hydrolyzing agent is immunoglobulin-degrading enzyme of Streptococcus pyogenes (IdeS) or a variant thereof.
Switzar describes “immunoglobulin-degrading enzyme of Streptococcus pyogenes (IdeS)” (page 1069) for sample preparation. Additionally, Switzar describes that “This bacterial cysteine protease specifically cleaves immunoglobulin G (IgG) under its hinge domain and cleaves the heavy chain into two fragments,41 whereas the streptococcal cysteine proteinase streptococcal exotoxin B (SpeB from the same bacterium) cleaves the heavy chains of all human immunoglobulins.42 IdeS digestion of IgG results in three protein fragments of ∼25 kDa (the light chain, and the VH−he1 and CH2−nd3 domains of the heavy chain) that could easily be separated and characterized by LC-ESI-QTOF MS.” (page 1069-1070), suggesting motivation to use this hydrolyzing agent when working with proteins.
Therefore it would have been obvious for one skilled in the art at the time the invention was filed to incorporate immunoglobulin-degrading enzyme of Streptococcus pyogenes (IdeS) hydrolyzing agent into the method of Tsao as suggested by Switzar because this would allow for the protein to be easily separated and characterized.
Regarding claims 17 and 18, Tsao describes the method of claim 11, however is silent to wherein preparing said samples for NMR spectroscopy includes a step of contacting said samples to at least one hydrolyzing agent and wherein said hydrolyzing agent is immunoglobulin-degrading enzyme of Streptococcus pyogenes (IdeS) or a variant thereof.
Switzar describes “immunoglobulin-degrading enzyme of Streptococcus pyogenes (IdeS)” (page 1069) for sample preparation. Additionally, Switzar describes that “This bacterial cysteine protease specifically cleaves immunoglobulin G (IgG) under its hinge domain and cleaves the heavy chain into two fragments,41 whereas the streptococcal cysteine proteinase streptococcal exotoxin B (SpeB from the same bacterium) cleaves the heavy chains of all human immunoglobulins.42 IdeS digestion of IgG results in three protein fragments of ∼25 kDa (the light chain, and the VH−he1 and CH2−nd3 domains of the heavy chain) that could easily be separated and characterized by LC-ESI-QTOF MS.” (page 1069-1070),, suggesting motivation to use this hydrolyzing agent when working with proteins.
Therefore it would have been obvious for one skilled in the art at the time the invention was filed to incorporate immunoglobulin-degrading enzyme of Streptococcus pyogenes (IdeS) hydrolyzing agent into the method of Tsao as suggested by Switzar because this would allow for the protein to be easily separated and characterized.
Regarding claim 19, the combination described above describes the method of claim 17, wherein said NMR spectra are 2D-NMR spectra (Tsao: [0068] “two-dimensional NMR (2D-NMR)”).
Regarding claim 20, the combination described above describes the method of claim 19, wherein said 2D-NMR spectra are obtained using a homonuclear NMR experiment through correlation spectroscopy (COSY), total correlation spectroscopy (TOCSY) or nuclear Overhauser effect spectroscopy (NOESY) (Tsao: [0068] “correlation spectroscopy magnetic-angle spinning NMR (COSY-NMR”).
Regarding claim 21, the combination described above describes the method of claim 19, wherein said 2D-NMR spectra are obtained using a heteronuclear NMR experiment through 1H-15N HSQC or 1H-13C HSQC (Tsao: [0068] “heteronuclear single-quantum coherence NMR (HSQC-NMR),” and [0027] “2D 1H-13C correlation spectrum”).
Claim(s) 9 and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsao et al. (US 2019/0079100 A1) in view of Amezcua et al. (JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 102, NO. 6, JUNE 2013, provided on the IDS on 1/25/2023).
Regarding claim 9, Tsao describes the method of claim 1, however is silent to wherein comparison includes applying ECHOS-NMR on said averaged NMR spectra from said at least two manufacturing processes.
Amezcua describes “easy comparability of HOS by NMR (ECHOS-NMR)” (abstract and page 1725). Additionally, Tsao describes “we analyzed the NMR data with easy comparability of HOS by NMR (ECHOS-NMR). This method couples the NMR fingerprinting principle with a simple statistical analysis to easily quantify the degree of structural similarity” suggesting motivation to use this technique when comparing NMR structures.
Therefore it would have been obvious to one skilled in the art at the time the invention was filed to incorporate ECHOS-NMR into the analysis of Tsao as suggested by Amezcua as this would allow “simple statistical analysis to easily quantify the degree of structural similarity”.
Regarding claim 22, Tsao describes the method of claim 11, however is silent to wherein comparison includes applying ECHOS-NMR on said averaged NMR spectra from said at least two manufacturing processes.
Amezcua describes “easy comparability of HOS by NMR (ECHOS-NMR)” (abstract and page 1725). Additionally, Tsao describes “we analyzed the NMR data with easy comparability of HOS by NMR (ECHOS-NMR). This method couples the NMR fingerprinting principle with a simple statistical analysis to easily quantify the degree of structural similarity” suggesting motivation to use this technique when comparing NMR structures.
Therefore it would have been obvious to one skilled in the art at the time the invention was filed to incorporate ECHOS-NMR into the analysis of Tsao as suggested by Amezcua as this would allow “simple statistical analysis to easily quantify the degree of structural similarity”.
Response to Arguments
Applicant's arguments filed 3/16/2026 have been fully considered but they are not persuasive.
The applicant argues that (1) that due to the amendments the 101 is overcome because it is now integrated into a practical application, (2) the multiple process of the prior art should not be considered different manufacturing processes, (3) the prior art only teaches averaging within one spectrum not over a plurality of samples as required by the claim, (4) the prior art does not describe “principal component analysis”, and (5) regarding claim 14, the prior art does not describes determining at least one area of said NMR spectra that contributes to at least one difference measured using principal component analysis, wherein said area is determined by plotting at least one loading as a contour plot on said NMR spectra.
In response to the applicant’s argument that (1) that due to the amendments the 101 is overcome because it is now integrated into a practical application, as noted in the rejection above there are no actual manufacturing steps provide. As such, it appears there is not a tangible application, and by extension, no practical application either.
In response to the applicant’s argument that (2) the multiple process of the prior art should not be considered different manufacturing processes, it is noted that the features upon which applicant relies (i.e., different manufacturing processes) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
In response to the applicant’s argument that (3) the prior art only teaches averaging within one spectrum not over a plurality of samples as required by the claim, as written in the claim this can be interpreted as “averaging said spectrum [individually] of each plurality of samples..”. Thus, under broadest reasonable interpretation this limitation is taught by Tsao.
In response to the applicant’s argument that (4) the prior art does not describe “principal component analysis”, in the rejection above the italicized portion is included to provided the definition of principal component analysis. Under broadest reasonable interpretation of “principal component analysis” meaning analysis of a large data set, the analysis performed by the method of Tsao reads on this definition and thus also principal component analysis.
In response to the applicant’s argument that (5) regarding claim 14, the prior art does not describes determining at least one area of said NMR spectra that contributes to at least one difference measured using principal component analysis, wherein said area is determined by plotting at least one loading as a contour plot on said NMR spectra, as noted in the rejection and response to arguments of claim 4 Tsao describes “determining at least one area of said NMR spectra that contributes to at least one difference measured using principal component analysis”. Furthermore, figure 1-4 of Tsao show “plotting at least one loading as a contour plot on said NMR spectra”. The claim 14 rejection has further been updated to include more specific reference to area determination.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY R BERKELEY whose telephone number is (571)272-9831. The examiner can normally be reached M-Th 9-6.
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/LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797
/EMILY R. BERKELEY/
Examiner
Art Unit 1796
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