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
Applicant(s) elected Group I, Claims 1-14, in response to the Election/Restriction mailed on 04/03/2026, as the elected subject matter. Group II, Claims 15-20, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The election was made without traverse in the reply filed on 05/28/2026.
Status of Claims
Claim 1-20 are pending with claims 1-14 under examination and claims 15-20 withdrawn from consideration.
Information Disclosure Statement
The information disclosure statement (IDS) document(s) submitted on 05/19/2025 is compliant with the provisions of 37 CFR 1.97. Accordingly, the IDS document(s) has/have been fully considered by the examiner.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tharmalingam et al. (A Framework for Real-Time Glycosylation Monitoring (RT-GM) in Mammalian Cell Culture, June 2015, Biotechnology and Bioengineering, Vol. 112, No. 6, pp. 1146-1154 – hereinafter “Tharmalingam”) where An et al. (Glycomics and Disease Markers, Current Opinion in Chemical Biology, December 2009, vol. 13, Issues 5-6, pp. 601-607; hereinafter “An”) is used as supporting documentation.
Regarding claim 1, Tharmalingam disclose a method (Tharmalingam; p. 1146, Abstract), comprising:
(a) obtaining a plurality of N-linked glycoproteins (Tharmalingam disclose an antibody-producing CHO cell line seeded in a proprietary chemically defined medium (“N-1 cultures”), where PNGase F enzyme is used to enzymatically release N-glycan species from samples; p. 1147, “Cell Line and Cell Culture”, pp. 1148-1149, “µSI-UPLC Glycan Map”. The examiner notes that use of PNGase F enzyme is well-known for releasing glycans from glycoproteins; see An p. 603, “Glycomics methods”, column 1, paragraph 3 – “Methods for releasing the glycans from glycoproteins depend on the attachment of the glycans. N-linked glycans (N-glycans) attach via nitrogen on an asparagine, while O-linked glycans (O-glycans) attach via oxygen at a serine or threonine. Reductive beta elimination is most common for releasing O-glycans, while Peptide N-Glycosidase F (PNGase F) enzymatic cleavage is the most common for releasing N-glycans”. Accordingly, Tharmalingam disclose a sample comprising N-linked glycoproteins);
(b) purifying the N-linked glycoproteins (Tharmalingam disclose “The system was programmed to take ~1 mL at 2 mL/min flow rate (~3 tubing volumes) of bioreactor sample to flush the sample line to avoid carryover, followed by the uptake of variable amounts of sample which was injected onto the Protein A [affinity] column”; pp. 1148-1149, Fig. 2, “Sample Cleanup”);
(c) measuring parameters of the N-linked glycoproteins (Tharmalingam disclose spectrophotometrically measuring concentrations in the bioreactor via UV-VIS fiber optic spectrometer, as well as viable cell density, viability, cell diameter, and titer; p. 1148, “The µSI-Glucose System”, fig. 1 & pp. 1149-1150, “Cell culture Performance”, fig. 3);
(optionally repeating steps (a) - (c)) (Tharmalingam disclose the system as a real-time glycosylation monitoring (RT-GM) framework for real-time monitoring of the antibody glycan profile; p. 1147, “Introduction”, column 2, paragraph 1);
(d) removing glycans from the N-linked glycoproteins (Tharmalingam disclose releasing glycan species from the sample using PNGase F; pp. 1148-1149, “µSI-UPLC Glycan Map”, Fig. 2, “Enzymatic Digestion”);
(e) labeling the glycans with a detectable label to form labeled glycans (Tharmalingam disclose glycan fluorescent labeling solution for labeling the glycans; pp. 1148-1149, “µSI-UPLC Glycan Map”, Fig. 2, “Glycan Labeling”);
(f) diluting the labeled glycans to a pre-determined concentration to form diluted labeled glycans (Tharmalingam disclose using various reagents for eluting the labeled glycans from a PGC column, thus diluting the labeled glycans; pp. 1148-1149, “µSI-UPLC Glycan Map”, Fig. 2, “Glycan Labeling”);
(g) enriching the diluted labeled glycans on a trap column to form enriched labeled glycans (Tharmalingam disclose the diluted labeled glycans are enriched using an Acquity UPLC Glycan BEH Amide Column; pp. 1148-1149, “µSI-UPLC Glycan Map”, Fig. 2, “Glycan Enrichment”); and
(h) detecting the enriched labeled glycans (Tharmalingam disclose A Waters Acquity UPLC system consisting of a fluorescence detector used to quantify the derivatized glycan species delivered from the µSI system; pp. 1148-1149, “µSI-UPLC Glycan Map”, Fig. 2, “UPLC Injection”).
Regarding claim 2, Tharmalingam disclose the method of claim 1 above, wherein the plurality of N-linked glycoproteins is from a bioreactor (Tharmalingam disclose an antibody-producing CHO cell line seeded in a proprietary chemically defined medium (“N-1 cultures”), where PNGase F enzyme is used to enzymatically release glycan species from samples; p. 1147, “Cell Line and Cell Culture”, pp. 1148-1149, “µSI-UPLC Glycan Map”. The examiner notes that use of PNGase F enzyme is well-known for releasing N-glycans from glycoproteins; see An p. 603, “Glycomics methods”, column 1, paragraph 3 – “Methods for releasing the glycans from glycoproteins depend on the attachment of the glycans. N-linked glycans (N-glycans) attach via nitrogen on an asparagine, while O-linked glycans (O-glycans) attach via oxygen at a serine or threonine. Reductive beta elimination is most common for releasing O-glycans, while Peptide N-Glycosidase F (PNGase F) enzymatic cleavage is the most common for releasing N-glycans”. Accordingly, Tharmalingam disclose a sample comprising N-linked glycoproteins).
Regarding claim 3, Tharmalingam disclose the method of claim 1 above, wherein the plurality of N-linked glycoproteins is from cultured cells (Tharmalingam disclose an antibody-producing CHO cell line seeded in a proprietary chemically defined medium (“N-1 cultures”), where PNGase F enzyme is used to enzymatically release glycan species from samples; p. 1147, “Cell Line and Cell Culture”, pp. 1148-1149, “µSI-UPLC Glycan Map”. The examiner notes that use of PNGase F enzyme is well-known for releasing N-glycans from glycoproteins; see An p. 603, “Glycomics methods”, column 1, paragraph 3 – “Methods for releasing the glycans from glycoproteins depend on the attachment of the glycans. N-linked glycans (N-glycans) attach via nitrogen on an asparagine, while O-linked glycans (O-glycans) attach via oxygen at a serine or threonine. Reductive beta elimination is most common for releasing O-glycans, while Peptide N-Glycosidase F (PNGase F) enzymatic cleavage is the most common for releasing N-glycans”. Accordingly, Tharmalingam disclose a sample comprising N-linked glycoproteins).
Regarding claim 4, Tharmalingam disclose the method of claim 1 above, wherein the plurality of N-linked glycoproteins comprises Fc domain-containing antibodies (Tharmalingam disclose an antibody-producing CHO cell line seeded in a proprietary chemically defined medium (“N-1 cultures”), where PNGase F enzyme is used to enzymatically release glycan species from samples; p. 1147, “Cell Line and Cell Culture”, pp. 1148-1149, “µSI-UPLC Glycan Map”. The examiner notes that use of PNGase F enzyme is well-known for releasing N-glycans from glycoproteins; see An p. 603, “Glycomics methods”, column 1, paragraph 3 – “Methods for releasing the glycans from glycoproteins depend on the attachment of the glycans. N-linked glycans (N-glycans) attach via nitrogen on an asparagine, while O-linked glycans (O-glycans) attach via oxygen at a serine or threonine. Reductive beta elimination is most common for releasing O-glycans, while Peptide N-Glycosidase F (PNGase F) enzymatic cleavage is the most common for releasing N-glycans”. Accordingly, Tharmalingam disclose an antibody-body producing bioreactor which comprise Fc domain-containing antibodies (monoclonal antibodies (mAbs)), p. 1146, Introduction, paragraphs 1-2).
Regarding claim 5, Tharmalingam disclose the method of claim 1 above, wherein the plurality of N-linked glycoproteins comprises Fc domain containing antibodies selected from: IgG, IgA, IgD, IgM, IgE, or any combinations thereof (Tharmalingam disclose an antibody-producing CHO cell line seeded in a proprietary chemically defined medium (“N-1 cultures”), where PNGase F enzyme is used to enzymatically release glycan species from samples; p. 1147, “Cell Line and Cell Culture”, pp. 1148-1149, “µSI-UPLC Glycan Map”. The examiner notes that use of PNGase F enzyme is well-known for releasing N-glycans from glycoproteins; see An p. 603, “Glycomics methods”, column 1, paragraph 3 – “Methods for releasing the glycans from glycoproteins depend on the attachment of the glycans. N-linked glycans (N-glycans) attach via nitrogen on an asparagine, while O-linked glycans (O-glycans) attach via oxygen at a serine or threonine. Reductive beta elimination is most common for releasing O-glycans, while Peptide N-Glycosidase F (PNGase F) enzymatic cleavage is the most common for releasing N-glycans”. Accordingly, Tharmalingam disclose an antibody-body producing bioreactor which comprise Fc domain-containing antibodies (monoclonal antibodies (mAbs)), p. 1146, Introduction, paragraphs 1-2).
Regarding claim 6, Tharmalingam disclose the method of claim 1 above, wherein purifying occurs by affinity chromatography (Tharmalingam disclose “The system was programmed to take ~1 mL at 2 mL/min flow rate (~3 tubing volumes) of bioreactor sample to flush the sample line to avoid carryover, followed by the uptake of variable amounts of sample which was injected onto the Protein A [affinity] column”; pp. 1148-1149, Fig. 2, “Sample Cleanup”).
Regarding claim 7, Tharmalingam disclose the method of claim 6 above, wherein purifying occurs by Protein A column; ion exchange column; or hydrophobic interaction chromatography (Tharmalingam disclose “The system was programmed to take ~1 mL at 2 mL/min flow rate (~3 tubing volumes) of bioreactor sample to flush the sample line to avoid carryover, followed by the uptake of variable amounts of sample which was injected onto the Protein A [affinity] column”; pp. 1148-1149, Fig. 2, “Sample Cleanup”).
Regarding claim 8, Tharmalingam disclose the method of claim 1 above, wherein the parameters comprise titer and concentration (Tharmalingam disclose spectrophotometrically measuring concentrations in the bioreactor via UV-VIS fiber optic spectrometer, as well as viable cell density, viability, cell diameter, and titer; p. 1148, “The µSI-Glucose System”, fig. 1 & pp. 1149-1150, “Cell culture Performance”, fig. 3).
Regarding claim 9, Tharmalingam disclose the method of claim 1 above, wherein measuring is by UV spectroscopy flow cell (Tharmalingam disclose spectrophotometrically measuring concentrations in the bioreactor via UV-VIS fiber optic spectrometer, as well as viable cell density, viability, cell diameter, and titer; p. 1148, “The µSI-Glucose System”, fig. 1 & pp. 1149-1150, “Cell culture Performance”, fig. 3).
Regarding claim 10, Tharmalingam disclose the method of claim 1 above, further comprising optionally repeating (a), (b), and (c) before (d) removing glycans (Tharmalingam disclose the system as a real-time glycosylation monitoring (RT-GM) framework for real-time monitoring of the antibody glycan profile; p. 1147, “Introduction”, column 2, paragraph 1).
Regarding claim 11, Tharmalingam disclose the method of claim 1 above, wherein removing glycans occurs by denaturing, deglycosylating, or any combinations thereof (Tharmalingam disclose releasing glycan species from the sample using PNGase F; pp. 1148-1149, “µSI-UPLC Glycan Map”, Fig. 2, “Enzymatic Digestion”).
Regarding claim 12, Tharmalingam disclose the method of claim 1 above, wherein the trap column is a hydrophilic interaction liquid chromatography (HILIC) column (Tharmalingam disclose the diluted labeled glycans are enriched using an Acquity UPLC Glycan BEH Amide Column; pp. 1148-1149, “µSI-UPLC Glycan Map”, Fig. 2, “Glycan Enrichment”).
Regarding claim 13, Tharmalingam disclose the method of claim 1, wherein detecting occurs by fluorescence-based detection (Tharmalingam disclose A Waters Acquity UPLC system consisting of a fluorescence detector used to quantify the derivatized glycan species delivered from the µSI system; pp. 1148-1149, “µSI-UPLC Glycan Map”, Fig. 2, “UPLC Injection”).
Regarding claim 14, Tharmalingam disclose the method of claim 1 above, wherein detecting further comprises: separating; detecting; and identifying the enriched labeled glycans (Tharmalingam disclose A Waters Acquity UPLC system consisting of a fluorescence detector used to separate and quantify the derivatized glycan species delivered from the µSI system; pp. 1148-1149, “µSI-UPLC Glycan Map”, Fig. 2, “UPLC Injection”).
Other References Cited
The prior art of made of record and not relied upon is considered pertinent to Applicant’s disclosure include:
Maley et al. (Characterization of Glycoproteins and Their Associated Oligosaccharides through the Use of Endoglycosidases, 1989, Analytical Biochemistry, 180, pp. 195-204) disclose PNGase F hydrolyzes N-linked oligosaccharides at the β-aspartylglycosylamine bond to yield ammonia, asparate, and an oligosaccharide with an intact di-N-acetyl-chitobiose on the reducing end.
Lauber et al. (Rapid Preparation of Released N-Glycans for HILIC Analysis Using a Labeling Reagent that Facilitates Sensitive Fluorescence and ESI-MS Detection, April 30, 2015, Analytical Chemistry, 87, 10, pp. 5401-5409) disclose a method for releasing and labeling N-glycan’s from monoclonal IgG antibodies and glycoproteins.
Hilliard et al. (Glycan characterization of the NIST RM monoclonal antibody using a total analytical solution: From sample preparation to data analysis, October 2017, Taylor & Francis Group, Vol. 9, No. 8, pp. 1349-1359) disclose a 1 hour sample preparation protocol for N-linked glycans.
Citations to art
In the above citations to documents in the art, an effort has been made to specifically cite representative passages, however rejections are in reference to the entirety of each document relied upon. Other passages, not specifically cited, may apply as well.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CURTIS A THOMPSON whose telephone number is (571) 272-0648. The examiner can normally be reached on M-F: 7:00 a.m. - 5:00 p.m..
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E-mail communication Authorization
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Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
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/C.A.T./Examiner, Art Unit 1798
/BENJAMIN R WHATLEY/Primary Examiner, Art Unit 1798
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