DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s election without traverse of Group I (drawn to an insoluble particle) and the species of and Fc region of SEQ ID NO:31 and an IgG of SEQ ID NO:5 in the Response filed on April 6, 2026 is acknowledged.
Claims 1-12 are pending.
Claims 5, 7, and 10-12 have been withdrawn under 37 CFR 1.142(b) as being drawn to nonelected inventions.
Claims 1-4, 6, 8, and 9 are currently under consideration as they read on the elected invention.
3. 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.
4. 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.
5. Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Schramm et al. (Clin. Chem. 1987 33;8:1338-1342) in view of Leatherbarrow et al. (FEBS Letters, 1983, 164;2:227-230) and Ju et al. (Current Opinion in Biotechnology 2014, 30:128-139).
Schramm et al. teach surface modification with protein A for uniform binding of monoclonal antibodies. Specifically, Schramm et al. teach optimal conditions for immobilization of two monoclonal antibodies to polystyrene (latex) surface refined with protein A (e.g. see Material and Method in right col. in page 1338). Schramm et al. teach that polystyrene surfaces refined with protein A achieve uniform, reproducible, stable and sterically accessible immobilization of IgG. Schramm et al. teach the polystyrene immobilized with the monoclonal antibodies provides superior performance of solid phase assays for quantitative immunoassays (e.g. left col. in page 1338).
The teachings of Schramm et al. differ from the instant invention by not describing aglycosylated antibody.
Leatherbarrow et al. teach aglycosylated IgG does not have major structural alterations at the CH2 and CH3 interface of the Fc region of IgG and no differences were found in binding to protein A (e.g. see Abstract). Leatherbarrow et al. teach that this indicates that protein A-Sepharose can be used for purification of aglycosylated IgG in the same manner as for the parent IgG.
Ju et al. teach aglycosylated full-length IgG antibodies that are nearly identical to the glycosylated counter parts in terms of antigen binding, stability at physiological or low temperature conditions, pharmacokinetics, and biodistribution (e.g. see Abstract). Ju et al. teach that in human IgGs, a complex N-glycan containing two highly dynamic branches is attached at each of Asn297 in the Fc regions (e.g. see 1st paragraph in left col. in page 130). Ju et al. teach several humanized aglycosylated IgG1 antibodies against specific antigens and wherein the antibodies have a N297A mutation and aglycosylated antibody produced in E. coli (without N297A substitution) (e.g. see right col. in page 131).
Ju et al. teach that aglycosylated monoclonal antibodies can be produced in eukaryotic hosts without the drawbacks of glycan heterogeneity resulting in costly and challenging downstream steps for purification and quality control. In addition, the use of aglycosylated full-length IgG antibodies is a great choice for a range of applications as receptor blocking, and targeted delivery not requiring to activate Fc binding ligand while possessing the beneficial prolonged serum half-life of IgG relative to antibody fragments and reduced undesired inflammation and cytotoxicity (e.g. see page 129).
It would thus be obvious to one of ordinary skill in the art at the time the invention was filed to combine the teachings of the references to produce a latex bound to aglycosylated IgG via protein A for immunoassays or immunopurification. An ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, because aglycosyalted monoclonal antibodies are known to be great choice for a range of applications as disclosed by Ju et al. Given that it was also known that aglycosylated IgG and the parent glycosylated IgG binds protein A with the same affinity, aglycosylated IgG can be immobilized to latex such as polystyrene the same way as the glycosylated parent IgG via protein A. Such aglycosylated antibody immobilized onto polystyrene would be expected to provide superior solid-phase immunoassays.
6. Claims 4, 6, 8, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Schramm et al. (Clin. Chem. 1987 33;8:1338-1342) in view of Leatherbarrow et al. (FEBS Letters, 1983, 164;2:227-230) and Ju et al. (Current Opinion in Biotechnology 2014, 30:128-139) as applied to claim 1 and 3 above, and further in view of Presta (US 6,737,056) and Chatterjee et al. (US 7,090,842).
The teachings of Schramm et al., Leatherbarrow et al., and Ju et al. have been discussed, above. Ju et al. teaches N297A and N297Q modifications in the Fc region of IgG antibodies (e.g. see Table 1 in page 132).
The reference teachings differ from the instant invention by not describing SEQ ID NO:5 not having a sugar chain-binding Asn-Xaa-Ser/Thr or SEQ ID NO:31 wherein Gln at position 174 is not mutated and a kit.
Instant SEQ ID NO:5 is the amino acid sequence of the constant region of murine IgG1 (e.g. see lines 4-5 in page 6 of the specification as-filed). SEQ ID NO:31 recited in instant claim 6 is the amino acid sequence is identical to SEQ ID NO:5 except Asn in position 174 is replaced with Gln (Q) (e.g. see lines 9-11 in page 8 of the specification as-filed).
Presta teaches human IgG1-4 and murine IgG1 has one and only identical N-glycosylation site, the tripeptide sequences NST (positions 297, 298, and 299) (e.g. see FIG.22A). Presta further teach the tripeptide sequence Asn-X-Ser/Thr, where X is any amino acid are the recognition sequence for enzymatic attachment of carbohydrate moiety to the Asn side chain. Presta teaches an amino acid substitution of residue N297A as variant does not bind Fcγ receptors (e.g. see last paragraph in col. 25 and Table 6 (REDUCED BINDING TO ALL FcγR).
Further, Presta teaches that as a matter of convenience, the reagents including the antibodies can be provided in an assay kit including packaged combination of reagents, assay plates (e.g. see col. 29).
Murine IgG1 antibodies having constant region of amino acid sequence of the instant SEQ ID NO:5 were well known at the time the instant invention was filed. For example, Chatterjee et al. teach a murine anti-idiotype antibody 3H1 having identical amino acid sequence of the instantly recited SEQ ID NO:5, e.g. see sequence alignments below:
RESULT 1
US-08-579-916F-9
(NOTE: this sequence has 10 duplicates in the database searched)
Sequence 9, US/08579916F
Patent No. 7090842
GENERAL INFORMATION
APPLICANT: Chatterjee, Malaya
APPLICANT: Kohler, Heinz
APPLICANT: Foon, Kenneth A.
APPLICANT: Chatterjee, Sunil K.
TITLE OF INVENTION: RECOMBINANT MONOCLONAL ANTI-IDIOTYPE ANTIBODY 3H1
TITLE OF INVENTION: SEQUENCES RELATING TO HUMAN CARCINOEMBRYONIC ANTIGEN
CURRENT APPLICATION NUMBER: US/08/579,916F
CURRENT FILING DATE: 28-Dec-1995
NUMBER OF SEQ ID NOS: 76
SEQ ID NO 9
LENGTH: 324
TYPE: PRT
Query Match 100.0%; Score 1747; Length 324;
Best Local Similarity 100.0%;
Matches 324; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSD 60
Qy 61 LYTLSSSVTVPSSPRPSETVTCNVAHPASSTKVDKKIVPRDCGCKPCICTVPEVSSVFIF 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYTLSSSVTVPSSPRPSETVTCNVAHPASSTKVDKKIVPRDCGCKPCICTVPEVSSVFIF 120
Qy 121 PPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSV 180
Qy 181 SELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKV 240
Qy 241 SLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMNTNGSYFVYSKLNVQKSNWEAGNTF 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMNTNGSYFVYSKLNVQKSNWEAGNTF 300
Qy 301 TCSVLHEGLHNHHTEKSLSHSPGK 324
||||||||||||||||||||||||
Db 301 TCSVLHEGLHNHHTEKSLSHSPGK 324
Chatterjee et al. teach that the antibody can be administered to induce an anti-carcinoembryonic antigen (CEA) response in gastrointestinal tract (e.g. see col. 2). Chatterjee et al. further teach that changes can be made in constant region for altered properties such as complement fixation and other effector functions (e.g. see col. 25).
It would thus be obvious to one of ordinary skill in the art to alter the consensus tripeptide sequence NST N-glycosylation site found in the Fc region of murine IgG1 the same way as human Fc region of IgG, namely N297A or N297Q to produce an aglycosylated murine IgG1. Such murine IgG1 Fc variant would inherently have the same amino acid sequence of the instant SEQ ID NO:5 and not having a sugar chain binding motif Asn-X-Ser/Thr given the N297A substitution, or having same amino acid sequence of SEQ ID NO:31 with N297Q substitution (wherein position 174 corresponding to position 297) would be a Q (not mutated).
An ordinary skill in the art would also be motivated to conjugate the aglycosylated murine IgG1 antibody to latex via protein A. Given the benefits of aglycosylated antibody in therapy and production (e.g. fast growth and simple quality control as shown in right col. in page 132 in Ju et al.) and in view of the knowledge that there is no difference in binding to protein A for aglycosylated murine IgG and glycosylated IgG as disclosed by Leatherbarrow et al., an ordinary skill in the art would have been motivated to produce aglycosylated murine IgG1 with amino acid substitutions N297A or N297Q and conjugate the algydocylated murine IgG1 to an insoluble latex particles for immunoassays and immunopurification as taught by Schramm et al. One of ordinary skill on the art would also be motivated to include all necessary components such as aglycosylated antibody and latex particles in a kit for convenience.
7. Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Vunnam et al. (US 5,585,278) in view of Ju et al. (Current Opinion in Biotechnology 2014, 30:128-139) and Leatherbarrow et al. (FEBS Letters, 1983, 164;2:227-230).
Vunnam et al. teach antibody-latex reagents prepared using a novel site-specific covalent linkage of the Fc region of the antibody onto the polymeric latex sphere substrates, thereby preserving the antigen binding sites of the antibody. Vunnam et al. teach that the immobilization of the antibody is essential for high specific activity and sensitivity assays and is also economical and much simpler than other covalent immobilizations (e.g. see Abstract and Examples).
The reference teachings differ from the instant invention by not describing aglycosylated antibody with no sugar chain bound to the heavy chain of the antibody.
The teachings of Ju et al. and Leatherbarrow et al. have been discussed above.
It would thus be obvious to one of ordinary skill in the art at the time the instant invention was filed to make a latex sphere immobilized with aglycosylated IgG antibody for immunoassays or immunodetection. An ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, because Vunnam et al. teach a novel site-specific covalent linkage of the Fc region of monoclonal IgG antibody to latex sphere that can be used as simple and economic immunoassay to detect antigen. Given that it was well known that therapeutic effects and benefit of aglycosylated IgG antibodies disclosed by Ju et al. and in view of the teachings of Leatherbarrow et al. that the removal of N-glycan in IgG does not affect the Fc properties in binding protein A, an ordinary skill in the art would be motivated to incorporate the aglycosylated therapeutic IgG to the latex beads for simple and sensitive methods disclosed by Vunnam et al. with a reasonable expectation of success.
8. Claim 4, 6, 8, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Vunnam et al. (US 5,585,278) in view of Ju et al. (Current Opinion in Biotechnology 2014, 30:128-139) and Leatherbarrow et al. (FEBS Letters, 1983, 164;2:227-230) as applied to claim 1 above, and further in view of Presta (US 6,737,056) and Chatterjee et al. (US 7,090,842).
The teachings of Vunnam et al., Ju et al., and Leatherbarrow et al. have been discussed above. The combined teachings of these references would yield predictable results of a latex beads conjugated with aglycosylated IgG monoclonal antibodies.
The reference teachings differ from the instant invention by not describing SEQ ID NO:5 not having a sugar chain-binding Asn-Xaa-Ser/Thr or SEQ ID NO:31 wherein Gln at position 174 is not mutated and a kit.
Note that instant SEQ ID NO:5 is the amino acid sequence of the constant region of murine IgG1 (e.g. see lines 4-5 in page 6 of the specification as-filed). SEQ ID NO:31 recited in instant claim 6 is the amino acid sequence is identical to SEQ ID NO:5 except Asn in position 174 is replaced with Gln (Q) (e.g. see lines 9-11 in page 8 of the specification as-filed).
Presta teaches human IgG1-4 and murine IgG1 has one and only identical N-glycosylation site, the tripeptide sequences NST (positions 297, 298, and 299) (e.g. see FIG.22A). Presta further teach the tripeptide sequence Asn-X-Ser/Thr, where X is any amino acid are the recognition sequence for enzymatic attachment of carbohydrate moiety to the Asn side chain. Presta teaches an amino acid substitution of residue N297A as variant does not bind Fcγ receptors (e.g. see last paragraph in col. 25 and Table 6 (REDUCED BINDING TO ALL FcγR).
Further, Presta teaches that as a matter of convenience, the reagents including the antibodies can be provided in an assay kit including packaged combination of reagents, assay plates (e.g. see col. 29).
Murine IgG1 antibodies having constant region of amino acid sequence of the instant SEQ ID NO:5 were well known at the time the instant invention was filed. For example, Chatterjee et al. teach a murine anti-idiotype antibody 3H1 having identical amino acid sequence of the instantly recited SEQ ID NO:5, e.g. see sequence alignments below:
RESULT 1
US-08-579-916F-9
(NOTE: this sequence has 10 duplicates in the database searched)
Sequence 9, US/08579916F
Patent No. 7090842
GENERAL INFORMATION
APPLICANT: Chatterjee, Malaya
APPLICANT: Kohler, Heinz
APPLICANT: Foon, Kenneth A.
APPLICANT: Chatterjee, Sunil K.
TITLE OF INVENTION: RECOMBINANT MONOCLONAL ANTI-IDIOTYPE ANTIBODY 3H1
TITLE OF INVENTION: SEQUENCES RELATING TO HUMAN CARCINOEMBRYONIC ANTIGEN
CURRENT APPLICATION NUMBER: US/08/579,916F
CURRENT FILING DATE: 28-Dec-1995
NUMBER OF SEQ ID NOS: 76
SEQ ID NO 9
LENGTH: 324
TYPE: PRT
Query Match 100.0%; Score 1747; Length 324;
Best Local Similarity 100.0%;
Matches 324; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYFPEPVTVTWNSGSLSSGVHTFPAVLQSD 60
Qy 61 LYTLSSSVTVPSSPRPSETVTCNVAHPASSTKVDKKIVPRDCGCKPCICTVPEVSSVFIF 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LYTLSSSVTVPSSPRPSETVTCNVAHPASSTKVDKKIVPRDCGCKPCICTVPEVSSVFIF 120
Qy 121 PPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPKPKDVLTITLTPKVTCVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSV 180
Qy 181 SELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SELPIMHQDWLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKV 240
Qy 241 SLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMNTNGSYFVYSKLNVQKSNWEAGNTF 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 SLTCMITDFFPEDITVEWQWNGQPAENYKNTQPIMNTNGSYFVYSKLNVQKSNWEAGNTF 300
Qy 301 TCSVLHEGLHNHHTEKSLSHSPGK 324
||||||||||||||||||||||||
Db 301 TCSVLHEGLHNHHTEKSLSHSPGK 324
Chatterjee et al. teach that the antibody can be administered to induce an anti-carcinoembryonic antigen (CEA) response in gastrointestinal tract (e.g. see col. 2). Chatterjee et al. further teach that changes can be made in constant region for altered properties such as complement fixation and other effector functions (e.g. see col. 25).
It would thus be obvious to one of ordinary skill in the art to alter the consensus tripeptide sequence NST N-glycosylation site found in the Fc region of murine IgG1 the same way as human Fc region of IgG, namely N297A or N297Q to produce an aglycosylated murine IgG1. Such murine IgG1 Fc variant would inherently have the same amino acid sequence of the instant SEQ ID NO:5 and not having a sugar chain binding motif Asn-X-Ser/Thr given the N297A substitution, or having same amino acid sequence of SEQ ID NO:31 with N297Q substitution (wherein position 174 corresponding to position 297) would be a Q (not mutated).
An ordinary skill in the art would also be motivated to conjugate the aglycosylated murine IgG1 antibody to latex sphere for immunoassay such as detecting an antigen.
Given the benefits of aglycosylated antibody in therapy and production (e.g. fast growth and simple quality control as shown in right col. in page 132 in Ju et al.) and in view of the knowledge that there is no difference in binding to protein A for aglycosylated murine IgG and glycosylated IgG as disclosed by Leatherbarrow et al., an ordinary skill in the art would have been motivated to produce aglycosylated murine IgG1 with amino acid substitutions N297A or N297Q and conjugate the algydocylated murine IgG1 to an insoluble latex particles for a simple and economic way of performing immunoassays as disclosed by Vunnam et al. One of ordinary skill on the art would also be motivated to include all necessary components such as aglycosylated antibody and latex particles in a kit for convenience following instructions in Presta.
9. No claim is allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHUN W DAHLE/Primary Examiner, Art Unit 1641
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