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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/9/2026 has been entered.
DETAILED ACTION
Claims 1-5, 8-11, 13-14, and 19-20 are pending and under examination on their merits. Claims 6-7, 12, and 15-18 are cancelled.
Response to Arguments
Applicant's arguments filed 2/9/2026 have been fully considered but they are not persuasive.
Applicant argues against the rejection of claims under 35 U.S.C. 112(a) on the grounds that written description under 35 U.S.C. § 112, first paragraph, does not depend on the breath of a claim or the scope of what the claims cover. Rather, the test for written description is whether what is claimed is adequately described in the application (Arguments, final full paragraph on page 5). Applicant argues that at least [0065]-[0088] and [0106] provide adequate written description support for the claimed methods and would allow one of skill in the art to recognize that the inventors had possession of the claimed subject matter at the time the application was filed (Arguments, final full paragraph on page 5, paragraph bridging pages 5-6).
In response, this argument is unpersuasive. Applicant seems to wish the examiner interpret the claim limitation narrowly in order to limit the claim to a scope that is supported by the written description provided within the specification. However, the broadest reasonable interpretation of “incubating the antibody preparation with trypsin under non-denaturing conditions at a total protein: trypsin ratio of 2,500:1 w/w to 10,000:1 w/w to thereby digest the contaminating protein while the antibody in the antibody preparation preferentially remains intact” is not limited to the non-denaturing conditions of Example 2 of the specification. For example, the claim does not recite “incubating the antibody preparation with trypsin without a denaturant at a total protein: trypsin ratio of 2,500:1 w/w to 10,000:1 w/w to thereby digest the contaminating protein while the antibody in the antibody preparation preferentially remains intact.” Non-denaturing conditions is a large genus of method conditions that encompasses any conditions in which a denaturant is not present. The person of ordinary skill in the art would not have recognized that Applicant had possession of the claimed genus of method conditions before the effective filing date of the claimed invention. Note that the claim amendment introduces an indefinite limitation that is discussed below in the rejection of claims under 35 U.S.C. 112(b).
Applicant argues against the rejection of claims under 35 U.S.C. 103 on the grounds that Huang developed the method specifically for high throughput sample analysis and to achieve a short cycle time. Thus, a skilled artisan would not have modified Huang by diluting the protein: trypsin ratio or replacing the chromatography with long gradient chromatography because both modifications would have resulted in longer digestion periods (Arguments, page 7, paragraph 2).
In response, this argument is unpersuasive because Thakur teaches that long gradient chromatography achieves high sensitivity at the sub-femtomole level (Abstract). Thus, the person of ordinary skill in the art would have turned to Thakur’s long gradient chromatography for the higher sensitivity. Regarding the protein: digest ratio, Fonslow teaches the parameters that control the digestion of proteins based on their abundance profiles and optimizes these parameters, which include the protein lysate concentration (units of mass/volume), trypsin concentration (units of mass/volume), and digestion depletion time (Supplementary Materials, bottom paragraph on page 24 and paragraph bridging pages 25-26). Thus, both digestion depletion time and trypsin concentration for a given amount of protein are variables that the person of ordinary skill in the art would have considered for optimization. The person of ordinary skill in the art would thus have considered a range of both protein: trypsin ratios as well as digestion times.
Applicant argues further that modifying Huang by Thakur results in changing their principles of operation because Thakur’s methods use reducing conditions and a significantly higher concentration of trypsin, whereas Huang does not use a reducing agent . Applicant asserts that Huang’s teachings do not use chromatography because they are analyzing host cell proteins in a pharmaceutical preparation, not the entire proteome. In contrast, Thakur’s methods were engineered to maximally digest every protein in the sample (Arguments, paragraphs 3-5 on page 7).
In response, Huang performs UPLC-MS/MS analysis of the tryptic digests (page 5437, right column, bottom paragraph), which comprises separating the peptides (UPLC is an acronym for ultra-performance liquid chromatography) and analyzing them by mass spectrometry (MS/MS is an acronym for tandem mass spectrometry) to identify and quantify the host cell proteins (Tables 2 and 4). Thus, Applicant’s statement that Huang does not use chromatography is incorrect. Furthermore, Applicant’s arguments seem to suggest that the examiner must rely on every teaching (such as the reducing conditions of Thakur) within each cited reference. Although each reference must be considered in its entirety, including disclosures that teach away from the claims (MPEP 2141.02(VI), "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed.” Here, the mere use of reducing conditions is not a teaching away of non-reducing conditions or a suggestion of incompatibility of the cited references. Furthermore, regarding the argument that modifying Huang by Thakur results in changing their principles of operation, replacing one form of chromatography in Huang (UPLC) with another form of chromatography (Thakur’s long gradient chromatography) is still chromatography.
Applicant argues further against the rejection of claims under 35 U.S.C. 103 on the grounds that Fonslow’s method employs a ratio of 25,000:1 protein: trypsin ratio, which is significantly lower than the presently claimed ratio. Applicant argues that the methods of Fonslow use a two-step digestion with both Lys-C and trypsin. Applicant argues that Fonslow’s digestion of the high abundance protein is in contrast to Huang’s teaching because in the methods of Huang, the antibody is the most abundant protein and it is preferentially undigested in the sample (Arguments, paragraph 2 on page 8). Thus, Applicant argues, the person of ordinary skill in the art would not have had a reasonable expectation of success that decreasing the trypsin concentration 62.5 times (from Huang’s 400:1 to Fonslow’s 25,000:1) would digest the host cell proteins Huang seeks to analyze (Arguments, paragraph 4 on page 8).
In response, this argument is unpersuasive because the rejection is not on the grounds of applying Fonslow’s protein: trypsin ratio to the method of Huang. Rather, the rejection is based on the grounds that Fonslow teaches the parameters that control the digestion of proteins based on their abundance profiles and optimizes these parameters, which include the protein lysate concentration (units of mass/volume), trypsin concentration (units of mass/volume), and digestion depletion time (Supplementary Materials, bottom paragraph on page 24 and paragraph bridging pages 25-26). Thus, it would have been obvious for the person of ordinary skill in the art to optimize the protein: trypsin ratio (the trypsin concentration for a given amount of protein).
Applicant argues that Meier teaches whole proteome coverage, whereas Huang teaches a method of analyzing residual host cell proteins (Arguments, page10, lines 1-2).
In response, this argument is unpersuasive because Huang and Meier are both still using mass spectrometry to analyze proteins.
Applicant argues against the rejection of claims under 35 U.S.C. 103 on the grounds that Applicant’s results are unexpected because compared to Huang, Applicant detects 296 host cell proteins whereas Huang detects 60 host cell proteins. (Arguments, bottom paragraph on page 10).
In order to establish that results are unexpected, the burden is on the applicant to establish results are unexpected and significant: “the evidence relied upon should establish that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance” (MPEP 716.02(b) I). Here, Applicant’s results are not unexpected. Per MPEP 716.02(a)(I): a greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected. Here, a greater than additive effect would have been expected because Meier’s BoxCar MS data acquisition methods teaches sensitivity improvements that are orders of magnitude better than Huang. Applicant’s results are also obvious in view of the prior art of Huang, Thakur, Fonslow, and Meier. The resulting improvement in HCP identification would have been predictable. Thakur’s long-gradient chromatography achieves high sensitivity (Abstract and page 2, left column, middle of second full paragraph). The optimization of the ratio of protein: trypsin in the digestion, which would have been obvious in light of the work of Fonslow, would likewise have been expected to increase HCP detection. Meier teaches that the sensitivity of BoxCar mass spectrometry is in the low atto-molar range (Abstract). Therefore, application of Meier’s BoxCar MS would also have increased HCP identification. In summary, the person of ordinary skill in the art would have expected that the method of Huang modified by Thakur, Fonslow, and Meier would have increased HCP identification by at least an order of magnitude given the sensitivity of BoxCar MS taught by Meier.
Applicant argues further against the rejection of claims under 35 U.S.C. 103 on the grounds that Chen teaches denaturing digestion conditions that have a much lower ratio of protein:trypsin (20:1). However, this argument is not pertinent to the claimed rejection, which only requires replacing Huang’s monoclonal antibody with any of the monoclonal antibodies taught by Chen.
The arguments presented by Applicant in the additional remarks filed 3/6/2026 merely summarize the arguments presented in the response filed 2/9/2026. Thus, these arguments are already addressed above.
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 1-5, 8-11, 13-14, and 19-20 are 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.
Claims 1 and 9 recite incubating the antibody preparation with trypsin under non-denaturing conditions at a total protein: trypsin ratio of 2,500:1 w/w to 10,000:1 w/w to thereby digest the contaminating protein while the antibody in the antibody preparation preferentially remains intact. Claims 1 and 9 are indefinite because there are at least two different reasonable interpretations of the claim. In one interpretation, the digestion conditions degrade more contaminating protein than antibody. In a second interpretation, this limitation is a preference and preferentially is synonymous with preferably. Under the second interpretation, the claim is further indefinite because it is unclear whether the limitation is optional or required.
Claims 2-5, 8, 10-11, 13-14, and 19-20 are rejected for depending from a rejected base claim and not rectifying the source of indefiniteness discussed above.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5, 8-11, 13-14, and 19-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claims 1 and 9 recite “A method for determining the identity or amount of a contaminating protein in an antibody preparation, comprising: incubating the antibody preparation with trypsin under nondenaturing conditions at a total protein:trypsin ratio of 2,500:1 w/w to 10,000:1 w/w to thereby digest the contaminating protein while the antibody in the antibody preparation preferentially remains intact.” The genus of non-denaturing trypsin digestion conditions is extremely broad, as the claim is not limited to an in-solution digestion and thus encompasses digestions performed on an immobilized support as well as those performed in solution. In addition, the duration of the incubation and the temperature required to digest the contaminating protein in the antibody preparation is not recited within the claim. Furthermore, the amount of the contaminating protein in the antibody preparation is not limited, thus the claim encompasses both low abundance and high abundance contaminating protein.
The person of ordinary skill in the art would not have recognized that the inventors had possession of the claimed genus of non-denaturing conditions that digest contaminating proteins, but not antibodies, in an antibody sample.
Applicant discloses a single set of conditions in which contaminating proteins in an antibody preparation are digested: Example 2, [00102]-[00104]. The only condition disclosed is the ratio of protein: trypsin, which ranges from 25,000:1 to 1,000:1 ([00102]). No other parameters of method conditions are disclosed (e.g. any necessary buffers, the required pH, any additional enzymes, the temperature of the incubation, or even the duration of the digest).
Huang (Analytical Chemistry 89.10 (2017): 5436-5444) teaches mixing an antibody solution with 1 M tris-HCl buffer, pH 8, and 90 µL of pure water, adding 5 µL of 0l.5 mg/mL recombinant bovine trypsin, 0.05 mg/mL ADH1 (“contaminating protein”), and 0.02 mg/mL hPCSK9 solution (“contaminating protein”), and incubating the preparations at 37°C overnight (page 5437, right column, “Tryptic Digest of IgG1 and IgG4 Samples Spiked with CHO Null Strain or CHO Proteins”). Huang teaches that contaminating proteins are preferentially digested (Abstract).
Thakur (cited in the Non-Final Action mailed on 4/17/2023) teaches first reducing proteins derived from HEK293 cells with 1 mM dithiotreitol and then alkylating with iodoacetamide (page 2, right column, In-Solution Digestion). HEK293 proteins are then digested with LysC for 3 h at a concentration of 1:50 (w/w) followed by overnight digestion with trypsin at a concentration of 1:50 (w/w) (page 2, right column, In-Solution Digestion).
Fonslow (cited in the Non-Final Action mailed on 4/17/2023) teaches denaturing and reducing protein samples, then digesting the proteins with trypsin at a 25,000:1 protein:protease mass ratio along with 1 mM CaCl2 for a 12h diffusion-limited digestion at 37 °C (page 57, “Digestion and depletion of abundant proteins”). Fonslow also teaches a 100:1 protein:protease mass ratio for digestion (Figure 1a).
In summary, although the prior art teaches various conditions for tryptic digestion of proteins in solution, with the exception of Huang, the prior art does not teach selectively digesting the contaminating protein and not the antibody. The person of ordinary skill in the art would have been unable to predict the entirety of non-denaturing conditions that selectively digest a contaminating protein, but not any antibody, based on the state of the art.
Based on the above analysis, the person of ordinary skill in the art would not have recognized that the inventors had possession of the claimed invention at the time the application was filed because the claimed genus of reaction conditions for the digestion is not commensurate in scope with the level of disclosure provided in the specification.
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.
Claims 1-5, 8-11, 13, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Analytical Chemistry 89.10 (2017): 5436-5444) in view of Thakur et al. (cited in the Non-Final Action mailed on 4/17/2023), Fonslow et al. (cited in the Non-Final Action mailed on 4/17/2023 and included with Supplementary Materials in this action), and Meier et al. (cited in the Non-Final Action mailed on 4/17/2023).
Huang teaches characterizing the identity and amount of the host cell proteins in an antibody sample by digesting the host cell proteins and leaving the antibody nearly intact (Abstract, Table 2, and Table 4). Huang teaches treating antibody samples with trypsin, followed by incubation with the reducing agent DTT, followed by heating in order to prepare antibody domains that precipitate and can be removed by centrifugation (page 5439, Results and Discussion, left column, second paragraph). Huang then performs UPLC-MS/MS analysis of the tryptic digests (page 5437, right column, bottom paragraph), which comprises separating the peptides (UPLC is an acronym for ultra-performance liquid chromatography) and analyzing them by mass spectrometry (MS/MS is an acronym for tandem mass spectrometry) to identify and quantify the host cell proteins (Tables 2 and 4). Huang also teaches that even if the antibody does not precipitate after incubating with DTT and heating, it is still possible to detect HCP because the reduced antibody is eluted later than most of the HCP tryptic peptides and does not interfere with detection (page 5443, left column, paragraph 1). Huang first performs the tryptic digest and does not include any denaturing agents (page 5437, right column, “Tryptic Digest of IgG1 and IgG4 Samples Spiked with CHO Null Strain or CHO Proteins”). Thus, Huang’s digestion is performed under non-denaturing conditions. Huang teaches that the trypsin digestion leaves the antibodies nearly intact while digesting the contaminating protein (Abstract).
Huang does not teach that the chromatography is long gradient liquid chromatography.
Thakur teaches that the combination of small particles, long columns, and long and shallow gradients (page 2, left column, middle of second full paragraph) achieves high sensitivity (sub-femtomole) and avoids the need for pre-fractionation (Abstract). Thakur teaches a column length of 50 cm and a gradient of 140 min or 480 min (Experimental Procedures, LC-MS Analysis, lines 1 and 5-6).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the technique of long gradient liquid chromatography in order to improve the method of Huang. One of ordinary skill in the art would have been motivated to improve the method sensitivity for detecting contaminating proteins. One of ordinary skill would have had a reasonable expectation of success given that Thakur demonstrates the large dynamic range of single run proteomics with long gradient chromatography by a triplicate analysis of both yeast cells (page 4, third full paragraph, lines 1-3) and human cells (page 6, Evaluation of Single LC-MS/MS Runs on a Human Cell Line, paragraph 1).
Huang and Thakur do not teach that the total protein:trypsin ratio is 2,500:1 w/w to 10,000:1 w/w.
Fonslow teaches the technique of ultra-low concentration trypsin digestion (Figure 1a, arrow labeled “with 25,000:1 protein:trypsin ratio”) in which highly abundant proteins are digested and depleted, followed by a standard concentration trypsin digestion in which the remaining lower abundance proteins are digested (Figure 1a, arrow labeled “100:1 protein:trypsin”). Fonslow derives a formula to explain the protease digestion of proteins to peptides (paragraph bridging pages 54-55 and formula (2)). Fonslow teaches the parameters that control the digestion of proteins based on their abundance profiles and optimizes these parameters, which include the protein lysate concentration (units of mass/volume), trypsin concentration (units of mass/volume), and digestion depletion time (Supplementary Materials, bottom paragraph on page 24 and paragraph bridging pages 25-26).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize by routine experimentation the ratio of protein to trypsin in Huang’s tryptic digest based upon the concentration of host cell proteins in Huang’s antibody preparation. The person of ordinary skill in the art would have been motivated to control the amount of digestion in order to maximize the number of detected host cell proteins. The person of ordinary skill in the art would have had a reasonable expectation of success given that Fonslow teaches the parameters that control protein digestion and also exemplifies two different protein:trypsin ratios that work for the enzymatic digestion of proteins with different abundance profiles (100:1 and 25,000:1 in Figure 1a).
Huang, Thakur, and Fonslow do not teach that the mass spectrometry is BoxCar MS (claims 1 and 8-9).
Meier teaches BoxCar mass spectrometry (a data-acquisition method) and demonstrates its application in proteomics (Discussion, paragraph 3, line 1). Meier teaches that the sensitivity of BoxCar mass spectrometry is in the low atto-molar range (Abstract). Meier teaches that BoxCar MS does not require any changes to the instrument hardware (Discussion paragraph 1). Meier teaches optimizing the effect of acquisition parameters on the number of quantified peptide features during BoxCar MS (page 441, left column, bottom paragraph). Meier teaches that to achieve cycle times around 1 s for the full acquisition cycle of one full scan, BoxCar scans and data-dependent MS2 scans were limited to two or three per acquisition cycle (page 441, left column, bottom paragraph). Therefore, Meier teaches “two or more scans of BoxCar MS” (claims 8-9) as well as “two or more scans of mass spectrometry (MS), wherein at least one scan is BoxCar MS” (claim 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply Meier’s technique of BoxCar MS (a data-acquisition method for mass spectrometry) in order to improve the method of Huang modified by Thakur and Fonslow. One of ordinary skill would have been motivated by the high sensitivity. The results of the method of Huang, Thakur, and Fonslow modified by Meier would have been predictable, especially since the application of the BoxCar MS technique would not have required any changes to the mass spectrometry instrument hardware and would have represented only a change in data acquisition.
Pertaining to claim 2, Huang teaches identifying the contaminating proteins by size and sequence (page 5438, paragraph bridging left and right columns).
Pertaining to claim 3, Huang teaches that the amount of contaminating protein is on the order of less than 10 ppm (Table 4). Meier teaches the detection of proteins on the order of attomoles as well as on the order of picomoles: “Protein abundance spanned more than six orders of magnitude and we estimated the amount of the 1,200 least abundant proteins to be < 10 attomoles” (see page 446, right column, paragraph 1, Figure 6c, and left chart of Supplementary Figure 8a). Therefore, the amount of contaminating protein that would have been detectable in the method of Huang modified by Thakur, Fonslow, and Meier would have been even less than the original method of Huang.
Pertaining to claims 5 and 10, Huang’s antibody is NIST monoclonal antibody standard RM 8670 (page 5441, right column “HCPs in NIST Monoclonal Antibody Standard RM 8670”), which is an antigen binding fragment.
Pertaining to claim 11, Huang’s contaminating proteins include cathepsin D (row 51 in Table 4).
Pertaining to claim 13, Huang does not teach the long gradient liquid chromatography comprises a 50 cm column and a gradient of 4 hrs.
Thakur teaches a column length of 50 cm and a gradient of 140 min or 480 min (Experimental Procedures, LC-MS Analysis, lines 1 and 5-6). Thakur compares the performance of the two different gradients (Figure 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize by routine experimentation the gradient to achieve the desired peptide separation. The person of ordinary skill in the art would have had a reasonable expectation of success given that Thakur exemplifies gradients of both 140 min and 480 min and compares the performance of the two different gradients (Figure 1). The person of ordinary skill in the art would have been able to predict the effect of the gradient on the peptide separation based on Thakur’s teaching.
Regarding claims 19-20, Huang teaches removing the antibody from the sample by precipitation prior to analyzing the digested peptides by UPLC-MS/MS (page 5437, left column, second paragraph, page 5438, Results and Discussion, left column, second paragraph).
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Analytical Chemistry 89.10 (2017): 5436-5444) in view of Thakur et al. (cited in the Non-Final Action mailed on 4/17/2023), Fonslow et al. (cited in the Non-Final Action mailed on 4/17/2023), and Meier et al. (cited in the Non-Final Action mailed on 4/17/2023), as applied to claims 1-5, 8-11, 13, and 19-20 above, further in view of Chen et al. (WO 2018/039499 Al; cited in the IDS filed on 4/3/2023).
See discussion of Huang, Thakur, Fonslow, and Meier above, which is incorporated into this rejection as well.
Pertaining to claim 14, Huang does not teach that the antibody is an anti-Ebola antibody, alirocumab, dupilumab, sarilumab, aflibercept, or rilonacept.
Chen teaches a method comprising digesting monoclonal antibody produced from RS001 CHO cells and injecting the digest into a reverse phase liquid chromatography column coupled to a triple quadrupole mass spectrometer (lines 3-5 of [00273]), thus quantifying the abundance of PLBD2 in the monoclonal antibody sample (lines 8-9 of [00273]). PLBD2 is a contaminating protein in the protein sample (see lines 1-5 of [00272]).
Chen teaches that the monoclonal antibody is selected from an anti-Ebola antibody, alirocumab, dupilumab, and sarilumab ([00172]) or an antibody fusion selected from aflibercept and rilonacept ([00173]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to replace Huang’s monoclonal antibody standard with any of the monoclonal antibodies taught by Chen. The person of ordinary skill in the art would have been motivated to apply the improved method of Huang modified by Thakur, Fonslow, and Meier to commercially relevant products. The person of ordinary skill in the art would have had a reasonable expectation of success given the antibodies Chen teaches are also monoclonal antibodies.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CANDICE LEE SWIFT whose telephone number is (571)272-0177. The examiner can normally be reached M-F 8:00 AM-4:30 PM (Eastern).
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657