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 1-16, filed 9/20/2022 are pending and considered on the merits below.
Information Disclosure Statement
The Information Disclosure Statements filed on 4/24/2023 and 3/6/2024 are in compliance with the provisions of 37 CFR 1.97 and have been considered. An initialed copy of the Form 1449 is enclosed herewith.
Drawings
The drawings are objected to because the figures are cut off in many places. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See at least specification [0237].
Claim Objections
Claim 2 is objected to because of the following informalities:
add a comma after “claim 1”
change “size-exclusion” to “size exclusion”.
Claim 6 is objected to because of the following informalities:
add a comma after “claim 1”
Claims 11 and 15 are objected to because of the following informalities:
Put a hyphen between host and cell.
Appropriate correction is required.
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 1-16 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.
Regarding claim 1, the limitation “a high molecular weight fraction” is a relative term which renders the claim indefinite. The term “a high molecular weight fraction” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For examination purposes the examiner interprets that a “high molecular weight fraction” is any fraction that has a higher molecular weight than an identified low molecular weight (LMW) species.
Claim 2 recites the limitation "the flow-through”. There is insufficient antecedent basis for this limitation in the claim. For examination purposes the examiner interprets that the claim reads “a flow-through”.
Regarding claim 13, the limitation “said denaturing” has a lack of antecedent basis as it depends from claim 11. For examination purposes the examiner interprets that the claim depends from claim 12.
Regarding claim 14, the limitation “characterizing” is indefinite because it is unclear if this is intended to take antecedent basis from the characterizing step in claim 1. For examination purposes the examiner interprets that the limitation reads “the characterizing”.
Dependent claim follow the same reasoning.
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) 1-4, 7-13, and 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hossler et al. (WO 2016/144773 Al).
Regarding claim 1, Hossler describes a method for characterizing host-cell proteins in a sample matrix (abstract and [00231] “the clarification and primary recovery of an antibody from a sample matrix”), comprising:
(a) enriching host-cell proteins in the sample matrix by contacting the sample matrix with a size exclusion chromatography support ([00322] “Size Exclusion Chromatography: Protein A purified antibody samples from Cell Line 1 were diluted when necessary to 0.5-5 mg/mL in IX PBS, and measured on a TSKgel® G3000SWXL column (Tosoh Bioscience, South San Francisco, CA) using an isocratic gradient on an HPLC with detection at 280 nm.”);
(b) collecting a high molecular weight fraction from said enriching ([00322] “High molecular weight (HMW), monomer, and low molecular weight (LMW) species were assigned and subsequently quantitated.”); and
(c) characterizing at least one of the host-cell proteins in said high molecular weight fraction using a mass spectrometer ([00334] “Protein A purified and the mAb-1 samples were analyzed for their N-glycan profiles via LC-MS of the reduced protein.”).
Regarding claim 2, Hossler describes the method of claim 1, further comprising washing the size-exclusion chromatography support with a wash buffer and collecting the flow-through ([00231] “Continuous and recycle chromatography are also applicable to chromatography methods where the protein is collected in the unbound faction during chromatography or where the protein is first bound to the chromatography resin and subsequently recovered by washing the media with conditions that elute the bound component.”)
Regarding claim 3, Hossler describes the method of claim 1, wherein the mass spectrometer is a tandem mass spectrometer ([00315] “N-glycan Glycopeptide Mapping-LC/MS/MS:”).
Regarding claim 4, Hossler describes the method of claim 3, wherein the mass spectrometer is coupled with a liquid chromatography system ([00315] “N-glycan Glycopeptide Mapping-LC/MS/MS:”).
Regarding claim 7, Hossler describes the method of claim 1, wherein the sample matrix further comprises a protein of interest ([00314] “N-glycan Oligosaccharide Profiling-LC/MS: The heavy chain of protein samples were analyzed”).
Regarding claim 8, Hossler describes the method of claim 7, wherein the protein of interest is an antibody ([0009] “methods for regulating the levels of high mannose N-glycans and N-glycan fucose of glycoproteins, such as antibodies like monoclonal antibodies (mAbs)”).
Regarding claim 9, Hossler describes the method of claim 7, wherein the protein of interest is a fusion protein ([0037] “Monoclonal antibodies are produced by methods known to those of skill in the art, for instance by making hybrid antibody-forming cells from a fusion of myeloma cells with immune spleen cells”).
Regarding claims 10 and 11, Hossler describes the method of claim 1, further comprising treating said high molecular weight fraction with a hydrolyzing agent and wherein an amount of said hydrolyzing agent used produces digestion of host cell proteins ([00315] “The proteins were digested with trypsin (1:20 trypsimantibody) (hydrolyzing agent) for 4 hours at 37 °c.”).
Regarding claims 12 and 13, Hossler describes the method of claim 1, further comprising denaturing said high molecular weight fraction and wherein said denaturing is carried out using heat ([00315] “Protein samples were denatured with 6M guanidine-HCl at pH 8.0... [and] reduced with 10 mM DTT for 30 minutes at 37 °C (heat).”).
Regarding claim 16, Hossler describes the method of claim 1, further comprising denaturing said high molecular weight fraction and treating said high molecular weight fraction with a hydrolyzing agent ([00315] “The proteins were digested with trypsin (1:20 trypsimantibody) (hydrolyzing agent) for 4 hours at 37 °c…. Protein samples were denatured with 6M guanidine-HCl at pH 8.0. ”).
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) 5-6 and 14-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hossler et al. (WO 2016/144773 Al) in view of Jain (DDT • Volume 10, Number 21 • November 2005).
Regarding claim 5, Hossler describes the method of claim 4, however is silent to wherein the liquid chromatography system is a nano-liquid chromatography system.
Jain describes method for characterizing proteins using a nano-liquid chromatography system (page 1439 “Nanoflow liquid chromatography”). Additionally Jain describes “miniaturized LC techniques were developed to allow for the analysis of samples with greater sensitivity than that afforded by conventional LC. In nanoflow LC (nanoLC), chromatographic separations are performed using flow rates in the low nanoliter per minute range, which result in high analytical sensitivity due to the large concentration efficiency afforded by this type of chromatography.” (page 1439). This suggest motivation to use nanoLC techniques when measuring biological sample because this would allow for higher analytical sensitivity.
Therefore it would have been obvious for one skilled in the art at the time the invention was filed to incorporate a nano-liquid chromatography system into the method of Hossler as suggested by Jain because this would allow for higher analytical sensitivity of detection.
Regarding claim 6, Hossler describes the method of claim 1, however is silent to further comprising characterizing at least one of the host-cell proteins using High-Field Asymmetric Waveform Ion Mobility Spectrometry device.
Jain describes method for characterizing proteins using High-field asymmetric waveform ion mobility spectrometry (page 1436 “High-field asymmetric waveform ion mobility spectrometry…(FAIMS)”). Additionally Jain describes “[FAIMS] facilitates the identification of low-abundance peptide ions, often present in part per million (ppm) levels as complex proteolytic digests, and expands the sensitivity and selectivity of nano liquid chromatography mass spectrometry (LC–MS).” (page 1436). This suggest motivation to use FAIMS techniques when measuring biological sample because this would allow for higher analytical sensitivity and selectivity.
Therefore it would have been obvious for one skilled in the art at the time the invention was filed to incorporate a High-field asymmetric waveform ion mobility spectrometry system into the method of Hossler as suggested by Jain because this would allow for higher analytical sensitivity and selectivity of detection.
Regarding claim 14, Hossler describes the method of claim 1, however is silent to wherein characterizing is carried out using parallel reaction monitoring.
Jain describes method for characterizing proteins using parallel reaction monitoring (page 1440 “Protein microarrays based on PWG allow the simultaneous, qualitative and quantitative analysis of protein interactions with high sensitivity in a parallel manner.”) This suggest motivation to use parallel reaction monitoring techniques when measuring biological samples because this would allow for higher sensitivity.
Therefore it would have been obvious for one skilled in the art at the time the invention was filed to incorporate parallel reaction monitoring into the method of Hossler as suggested by Jain because this would allow for higher sensitivity of detection.
Regarding claim 15, Hossler describes the method of claim 1, however is silent to wherein one of said host cell proteins is C-C motif chemokine.
Jain describes method for characterizing proteins and host cell proteins are C-C motif chemokines (page 1440 “CCR5, CXCR4 and other membrane proteins (these are C-C motif chemokines)”). Additionally, Jain describes “This approach has implications for drug discovery in which binding of small molecules to 7-transmembrane (and other membrane) receptors could be measured.” (page 1440). This suggest motivation to use host cell proteins that are C-C motif chemokines when measuring biological sample because this would allow for novel drug discovery.
Therefore it would have been obvious for one skilled in the art at the time the invention was filed to use host cell proteins that are C-C motif chemokines in the method of Hossler as suggested by Jain because this would allow for novel drug discovery.
Conclusion
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Elizabeth Robinson can be reached at 571-272-7129. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMILY R. BERKELEY/
Examiner
Art Unit 1796
/ELIZABETH A ROBINSON/Supervisory Patent Examiner, Art Unit 1796