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 .
Detailed Action
This is the Non-Final Action for application 18/221934 filed 07/14/2023.
Claims 1-2 are pending and have been fully considered.
This application was examined as part of the PBA program.
Claim Rejections - 35 USC §103
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 is rejected under 35 U.S.C. 103 as being obvious over LIU in US 20080206102 in view of MADDEN in Reverse Isoelectric Focusing Procedure Resolves Charge Variants of Basic Proteins.
With respect to Claim 1, LIU teaches of a method and device for simultaneous separation, fractionation, and collection of samples simultaneously (abstract). LIU further teaches that the method uses isoelectric focusing (IEF) in capillary tubes (paragraph 0023). LIU teaches that the separation is based on the charge properties (charges and charge variants) of the protein and sample (paragraph 0004).
LIU further teaches the IEF sample is prepared by mixing ampholytes with a protein sample (paragraph 0025-0027), the sample is the loaded into the continuous capillary (the thin-line of FIG. 1A) (paragraph 0029), and then the IEF is run (paragraph 0030) which reads on instant step a) that the sample including protein of interest is subjected to isoelectric focusing to separate said charge variant of protein of interest as claimed.
The proteins are collected inside the segmented capillaries. It is noted that although the sample is "split" into 100 fractions, proteins of similar pI are "focused" in one or two (combined) fractions after IEF (paragraphs 0030-0031, & 0023 & 0035). This reads on the instant step b), which requires collecting, “at least one,” fraction, and also instant step c) which requires repeating steps a) and b) “at least once,” since the 100 initial fractions read on repeating the IEF, and collecting “two,” fractions reads on repeating the collecting. Since the 100 fractions are narrowed down to two collected samples, this means that from the 100 samples the proteins of interested are collected and combined into one or two samples as claimed for instant step d).
LIU even further teaches that non-equilibrium pH gradient electrophoresis (NEpHGE) is typically used to resolve extremely basic proteins. It differs from the other two types of isoelectric electrophoresis in that: (i) the polarity of the power supply is reversed at a predetermined volt-hour value during the separation; and (ii) the focusing process is stopped before reaching equilibrium (paragraph 0004-0005). This reads on the instant “reversed polarity isoelectric focusing.”
Protein “enrichment,” is the concentrating of specific proteins or making them more abundant for analysis. LIU teaches of concentration of the proteins by IEF so this reads on the claimed “method for enriching,” (paragraph 0016). The protein separated is the “charge variant,” of the protein of interest (paragraph 0004).
LIU does not name the electrophoresis used, reversed.
MADDEN is used to remedy this. MADDEN further teaches of reverse isoelectric focusing for resolving charge variants of basic proteins (title). MADDEN further teaches that NEPHGE, nonequilibrium pH gradient electrophoresis is used (Page 203, column 2, paragraphs 1-2), and that they have chosen to call this procedure “reverse IEF,” (page 203, column 1, paragraph 1) and that this technique resolves/separates charge variants of basic proteins (title). NEPHGE, which MADDEN names reverse IEF, is the same method used in LIU.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to use the NEPHGE /reversed IEF method of MADDEN in the method of LIUE due to the need in the art for a simple, rapid method for analyzing levels of processed and unprocessed proteins and the advantage the method use in LIU offers for this purpose (Page 203, column 2, last paragraph).
Claim 2 is rejected under 35 U.S.C. 103 as being obvious over LIU in US 20080206102 in view of MADDEN in Reverse Isoelectric Focusing Procedure Resolves Charge Variants of Basic Proteins and further in view of GENTALEN in US 20210181148.
With respect to Claim 2, LIU teaches of a method and device for simultaneous separation, fractionation, and collection of samples simultaneously (abstract). LIU further teaches that the method uses isoelectric focusing (IEF) in capillary tubes (paragraph 0023). LIU teaches that the separation is based on the charge properties (charges and charge variants) of the protein (charge variant of interest) and sample (paragraph 0004).
LIU further teaches the IEF sample is prepared by mixing ampholytes with a protein sample (paragraph 0025-0027), the sample is the loaded into the continuous capillary (the thin-line of FIG. 1A) (paragraph 0029), and then the IEF is run (paragraph 0030) which reads on instant step a) that the sample including protein of interest is subjected to isoelectric focusing to separate said charge variant of protein of interest as claimed.
The proteins are collected inside the segmented capillaries. It is noted that although the sample is "split" into 100 fractions, proteins of similar pI are "focused" in one or two (combined) fractions after IEF (paragraphs 0030-0031, & 0023 & 0035). This reads on the instant step b), which requires collecting, “at least one,” fraction, and also instant step c) which requires repeating steps a) and b) “at least once,” since the 100 initial fractions read on repeating the IEF, and collecting “two,” fractions reads on repeating the collecting. Since the 100 fractions are narrowed down to two collected samples, this means that from the 100 samples the proteins of interested are collected and combined into one or two samples as claimed for instant step d).
LIU even further teaches that non-equilibrium pH gradient electrophoresis (NEpHGE) is typically used to resolve extremely basic proteins. It differs from the other two types of isoelectric electrophoresis in that: (i) the polarity of the power supply is reversed at a predetermined volt-hour value during the separation; and (ii) the focusing process is stopped before reaching equilibrium (paragraph 0004-0005). This reads on the instant “reversed polarity isoelectric focusing.”
Protein “enrichment,” is the concentrating of specific proteins or making them more abundant for analysis. LIU teaches of concentration of the proteins by IEF so this reads on the claimed “method for enriching,” (paragraph 0016). The protein separated is the “charge variant,” of the protein of interest (paragraph 0004).
LIU does not name the electrophoresis used, reversed.
MADDEN is used to remedy this. MADDEN further teaches of reverse isoelectric focusing for resolving charge variants of basic proteins (title). MADDEN further teaches that NEPHGE, nonequilibrium pH gradient electrophoresis is used (Page 203, column 2, paragraphs 1-2), and that they have chosen to call this procedure “reverse IEF,” (page 203, column 1, paragraph 1) and that this technique resolves/separates charge variants of basic proteins (title). NEPHGE, which MADDEN names reverse IEF, is the same method used in LIU.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to use the NEPHGE /reversed IEF method of MADDEN in the method of LIUE due to the need in the art for a simple, rapid method for analyzing levels of processed and unprocessed proteins and the advantage the method use in LIU offers for this purpose (Page 203, column 2, last paragraph).
LIU and MADDEN teach of the claims as shown above, but do not teach of using ion exchange chromatography prior to the isoelectric focusing.
GENTALEN is used to remedy this. GENTALEN teaches of a method for characterization of analyte mixtures are provided. Some methods described herein include performing enrichment steps on a device before expelling enriched analyte fractions from the device for subsequent analysis (abstract). More specifically, GENTALEN teaches that the method is for separating a mixture of charge variants of one or more biologics (Claim 31), which can be proteins (paragraph 0009-0010).
GENTALEN more specifically teaches that ion exchange chromatography can be used for chromatographic separation (paragraph 0045-0046), and that enriching the sample can include ion exchange chromatography and isoelectric focusing (paragraph 0076, 0100, 0101). GENTALEN further teaches that any combination of components and features described therein can be used together (paragraph 0137).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to use ion exchange chromatography in addition to isoelectric focusing as is done in GENTALEN in the methods of LIU and MADDEN due to the advantage ion exchange offers for capturing analytes based on charge (GENTALEN, paragraph 0046, 0101).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758