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 .
This is the Final Office Action for application 17/779104, response filed 10/21/2205.
Claims 1, 3, 8, 13, 16, 18, 20-21, 23, 27-31, 35, 38-39 are pending and have been fully considered.
Claims 2, 4-7, 9-12, 17, 19, 22, 24-26, 32-34, 36-37 & 40-44 are cancelled.
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.
Claim 1 and those dependent therefrom 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.
Claim 1 recites the limitation "releasing one or more N-linked glycans from the recombinant protein.” There is insufficient antecedent basis for this limitation in the claim because there is no positive step of “providing a recombinant protein.” Applicant can rectify the lack of antecedent basis by incorporating a step of "providing a recombinant protein without any label" in the body of the claim. *What is currently in the preamble of the claim is not limiting since a recitation of the intended use of a method in the preamble is nonlimiting.
Claims 3, 8, 13, 16, 18, 20-21, 23, 27-31, 35, 38-39 are rejected by virtue of their dependency on Claim 1.
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 1, 3, 8, 13,16,18, 20, 23,27,28,29,30,31,35, and 39 are rejected under 35 U.S.C. 103 as being obvious by CHEMMALIL in US 20180321252 in view of in view of BOSQUES in US 20060057638.
With respect to Claim 1, CHEMMALIL teaches a method of quantification of glycan moiety in recombinant glycoproteins (title) which has been read on the claimed “A method of quantifying a glycosylation profile of a recombinant protein, without any label”; paragraph [0008] further discloses that the method comprises digesting the recombinant glycoprotein with an enzyme which has been read on the claimed “releasing one or more N-linked glycans are released from the recombinant protein by an enzyme prior to the analysis”; paragraph [0031] discloses that after the glycan moiety is liberated from the recombinant glycoprotein, a separation step can be used in improving the detection capability of the method of the invention. The liberated glycan moiety can be separated by any number of techniques, including chromatography. This has been read on the claimed “separating the released N-linked glycans using a chromatography column.”
Finally paragraph [0026] discloses that a charge aerosol detector CAD is used for the detection of analytes as is a closely sensitive detector to NQAD, which has been read on the claimed “wherein the one or more N-linked glycans that are separated are measured by a charged aerosol detector (CAD).”
CHEMMALIL teaches the method as shown above. CHEMMALIL is silent regarding silent regarding the column being a porous graphite carbon (PGC) column.
However, BOSQUES discloses using porous graphite carbon (PGC) columns in order to purify glycans (see: paragraph [0092]).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of CHEMMALIL to include the PGC column as disclosed by BOSQUES, in order to get the benefits of PGC columns that BOSQUES describes in paragraph [0165], such as retaining both neutral and charged sugars, while allowing salts to be washed away.
With respect to Claim 3, CHEMMALIL teaches the method of claim 1. CHEMMALIL is silent regarding the purity of the recombinant protein.
However, BOSQUES teaches in paragraph [0140] that the protein sample can be at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or more pure. It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of CHEMMALIL, to include the purities disclosed by BOSQUES, to get the benefits that BOSQUES states in paragraph [0141] that knowing the glycosylation of a protein (i.e. the purity) can be used for the diagnosis of any disease or condition that is caused or results in changes in protein glycosylation. For example, the methods provided can be used in the diagnosis of cancer, inflammatory disease, benign prostatic hyperplasia (BPH), etc.
With respect to Claim 8, CHEMMALIL, paragraph [0029] indicates that glycosidase enzymes are used, which has been read on the claimed “wherein the enzyme comprises peptide N-glycosidase F (PNGaseF).”
With respect to Claim 13, CHEMMALIL, paragraph [0047] indicates that a mixed mode column was used which has been read on the claimed “The method of claim 1[[4]], wherein the column is a mixed mode column.”
With respect to Claims 16 & 18, CHEMMALIL, in Section 3.1 Optimization of Chromatography, paragraph [0059]- [0064] detail the use of formic acid, and Trifluoroacetic acid (TFA) as first and second mobile phases, describing their uses in “mobile phases A & B”. Furthermore, paragraph [0049], discloses that Triethylamine was used as an initial mobile phase when conducting initial screening of HPLC columns with various chemistries. Paragraphs [0056] and [0057] disclose that Triethylamine was also used as a mobile phase when evaluating the column.
With respect to Claim 20, CHEMMALIL in view of BOSQUES teach the method of claim 7. CHEMMALIL further discloses in Section 3.1 Optimization of Chromatography, paragraph [0064] that the column temperature was kept at ambient, which has been read on the claimed “wherein the separation is performed at a temperature lower than 70 °C.”
With respect to Claim 23, CHEMMALIL, in Section 3.1 Optimization of Chromatography, paragraph [0064] and [0065] indicate that a gradient was used and was optimized, which has been read on the claimed “wherein the separation is on a gradient.”
With respect to Claim 27, CHEMMALIL, paragraph [0023] discloses that the methods of the invention can be used to analyze glycan moieties including N-glycans. Galactose (Gal), N-acetyl-glucosamine (GlcNAc), Glucose (Glc), N-Acetylglucosamine (GlcNAc), Mannose (Man), N-Acetylmannosamine (ManNAc), and Fucose (Fuc) are explicitly disclosed as examples. Furthermore, more complex combinations of one or more type of such moieties, such as mono-antennary, bi-antennary, tri-antennary, tetra-antennary, and higher order structures can also be analyzed. Any number of post-translational modifications of glycoproteins can similarly be determined and quantitated using the methods of the invention described. This has been read on the claimed “wherein the one or more N-glycans are Galactose (Gal), N-Acetylgalactosamine (GalNAc), Galactosamine (GalN), Glucose (Glc), N-Acetylglucosamine (GlcNAc), Glucosamine (GlcN), Mannose (Man), N-Acetylmannosamine (ManNAc), Mannosamine (ManN), Xylose (Xyl), N- Acetylneuraminic acid (Neu5Ac), N-Glycolylneuraminic acid (Neu5Gc), 2-Keto-3- deoxynononic acid (Kdn), Fucose (Fuc), Glucuronic Acid (GlcA), Iduronic acid (IdoA), Galacturonic acid (GalA), Mannuronic acid (ManA), or any combination thereof.”
With respect to Claim 28, CHEMMALIL, paragraph [0023] discloses that the methods of the invention can be used to analyze glycan moieties including N-glycans. Furthermore, more complex combinations of one or more type of such moieties, such as bi-antennary structures can also be analyzed. This has been read on the claimed “wherein the one or more N-glycans comprise one or more bi-antennary glycans.”
With respect to Claim 29, CHEMMALIL, paragraph [0023] discloses that the methods of the invention can be used to analyze glycan moieties including N-glycans. Furthermore, more complex combinations of one or more type of such moieties, such as bi-antennary structures can also be analyzed. This has been read on the claimed “wherein the bi-antennary glycans are selected from a group consisting of GOF, GO, G1F, G1, G2F, G2,[[ ,]] S1G2F, S1G2, S2G2F, S2G2 and any combination thereof.”
With respect to Claim 30, CHEMMALIL, paragraph [0007] indicates that the invention is particularly suitable for determination of sialic acid moiety on a recombinant glycoprotein, which has been read on the claimed “wherein the glycosylation profile comprises one or more asialylated glycans, mono-sialylated glycans, di- sialylated glycans, and/or tri-[[ ]]sialylated and tetra-sialylated glycans.”
With respect to Claim 31, CHEMMALIL, paragraph [0007] discloses the recombinant protein can be an antibody, which has been read on the claimed “wherein the recombinant protein is an antibody.”
With respect to Claim 35, CHEMMALIL, paragraph [0007] discloses the recombinant protein can be an antibody, which has been read on the claimed “wherein the antibody is an anti-GITR antibody, an anti-CXCR4 antibody, an anti-CD73 antibody, an anti- TIGIT antibody, an anti-0X40 antibody, an anti-LAG3 antibody, an anti-CSF1R antibody, or an anti-IL8 antibody.”
With respect to Claim 38, CHEMMALIL, paragraph [0007] discloses that the recombinant protein can be a hormone or a cytokine, which has been read on the claimed “wherein the recombinant protein comprises an enzyme, a hormone, a cytokine, a cell surface receptor, a protease, a cytokine receptor, or any combination thereof.”
With respect to Claim 39, CHEMMALIL, paragraph [0007] discloses that the recombinant protein can be a fusion protein, which has been read on the claimed “wherein the recombinant protein is a fusion protein.”
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over CHEMMALIL in US 20180321252 in view of BOSQUES in US 20060057638 and further in view of HEIDORN in The Role of Temperature and Column Thremostatting in Liquid Chromatography.
With respect to Claim 21, CHEMMALIL in view of BOSQUES teaches the method of claim 20. They do not teach wherein the temperature is between about 50 °C and about 70 °C.
HEIDORN indicates (Fig 2) that operating temperatures between 30 – 110 0C are used in chromatography columns. Fig 2. Explicitly shows a chromatography run done at 50 0C, and 70 0C, as well as an operating temperature between 50 0C and 70 0C. HEIDORN indicates that increasing the separation temperatures to these temperatures which are above ambient is used to shorten the analysis time, to improve separation efficiency, to achieve a lower system backpressure or to obtain alternative selectivities with polar sample compounds (see also Fig. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of claim 20 with the conditions cited by HEIDORN, to get the benefits as stated above.
Response to Arguments
Applicant's arguments filed 10/21/2025 have been fully considered but they are not persuasive.
Applicant has overcome 1 of the priorly mentioned 112 (b), issues but 1 remains. Since, “providing a recombinant protein without any label," is claimed—it is unclear how or what the N-linked glycans are released from in step a). Therefore, the 112 (b) rejection is maintained.
With respect to the 102 rejection—it is overcome due to amendments made 10/21/2025, however the 103 rejection still applies for the amended claims. In arguing about the 102 rejection applicant notes that the examiner did not consider prior Claim 7 to be anticipated, and has thus amended the subject matter of prior Claim 7 into that of Claim 1. With respect to this--- the examiner notes that Claim 7 was priorly rejected not under 102, but under 103 in view of both CHAMMALIL and BOSQUE. Further, the examiner notes that applicant has not amended into the claims the exact claim language of prior Claim 7, and the “mixed mode,” part that was priorly in Claims 5 & 7 has not been included in the amendment. Further- the examiner notes that the subject matter or prior Claim 12- which was formerly only dependent on Claim 1 was also amended into independent Claim 1.
With respect to the 103 rejection of CHEMMALIL in view of BOSQUE, applicant argues that CHEMMALIL teaches away from the use of charged aerosol detector (CAD) in favor of NQAD and that CHEMMALIL teaches that there are drawbacks to using CAD instead of NQAD, therefore one wouldn’t have reasonable expectation of success. The examiner disagrees, as though CHEMMALIL focuses on NQAD, as taught by CHEMAMLIL, CAD is next in line from NQAD as a sensitive detector--- therefore though teaching NQAD is preferred, is still teaching of CAD and this is not teaching away from using CAD, is just teaching a preference for NQAD (paragraph 0026).
Applicant further argues with respect to the 103 rejection that no reference teaches of detection with CAD and also measuring using a porous graphite carbon. The examiner notes that the fact that CHEMALIL does not teach of the porous graphite carbon is the exact reason why a secondary reference, BOSQUE was used.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant further argues that “in view of the poor performance expected from the CAS systems in CHEMAMLIL, it would be unexpected that combining a porous graphite carbon column with a charged aerosol detector would result in a very efficient system.” With respect to this--- the examiner notes that this argument is not commensurate in scope with the claims as nothing about system efficiency nor parameter which might be a marker of system efficiency is claimed.
All claims remain rejected.
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 Rebecca Fritchman whose telephone number is (303)297-4344. The examiner can normally be reached Monday-Friday 8:00am- 5p.m. EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached at 571 270 7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/REBECCA M FRITCHMAN/ Primary Examiner, Art Unit 1758
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