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 .
1. The Amendment filed February 3, 2026 in response to the Office Action of November 4, 2025, is acknowledged and has been entered. Claims 26, 31, 34-36, 41, 43, 47, 58-67 are pending and being examined. Claims 1-25, 27-30, 32-33, 37-40, 42, 44-46, 48-57 are canceled. Claims 26, 31, 35, 36, 43, 47 are amended. Claims 58-67 are new.
The claims are amended, and new claims are added, altering the scope of the previously examined claimed invention, and adding limitations of specific antibody sequences, 100 mg/ml antibody, and intramuscular injection, necessitating the new rejection set forth below.
Claim Objections
2. Claim 43 is objected to because of the following informalities: Claim 43 was amended to recite “about 24 mM sucrose”, however, Examiner believes that is an inadvertent typo and should recite “240 mM sucrose”. Appropriate correction is required.
New Rejection
(necessitated by amendments)
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.
3. Claim(s) 26, 31, 34-36, 41, 43, 47, 58-67 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2022/026592, Hirsh et al, filed July 28, 2021, claiming priority to July 28, 2020; in view of Strickley and Lambert (Journal of Pharmaceutical Sciences, 2021, 110:2590-2608; published online March 28, 2021) US Patent Application Publication 2021/0300999, Crowe et al, filed March 25, 2021, published September 30, 2021; and US Patent Application Publication 2022/0025071, Capon, filed July 21, 2021, claiming priority to July 10, 2020.
Hirsh teaches a pharmaceutical composition comprising a formulation of:
a SARS-CoV-2 anti-spike protein antibody or antigen-binding fragment thereof;
histidine buffer;
sucrose carbohydrate;
arginine; and
polysorbate 80;
wherein the formulation has a pH in the range of 5.0 to 6.5, or 5.0 to 6.0, or 5.5 to 6.5 (p. 19, 196, 218-219, 234-235);
wherein the antibody is present at an amount of about 100 mg/ml (p. 19, 195, 219, 235);
wherein the polysorbate 80 is present at 0.03% to 0.05% (w/v), or about 0.04% (w/v) (p. 20, 197-198, 219, 225, 235); and
wherein the sucrose is present at 6% to 10% (w/v), or 8% (w/v) (p. 20, 197-198, 225, 235).
It is noted that the conversion to mM for sucrose at 8% w/v is 233 mM, and the conversion to mM for sucrose at 10% w/v is 292 mM. For example, the molar mass of sucrose is ~ 342 g/mol. The molarity for 8% w/v sucrose = 80x10 g/L / 342 g/mol = 0.23 M = 233 mM, which is “about 240 mM sucrose”.
Hirsh teaches the pharmaceutical composition comprises antibody at a concentration of about 100 mg/mL (p. 19, 196-197, 219, 235).
Hirsh teaches the pharmaceutical composition is formulated for intramuscular administration (p. 19, 193, 196-197, 219; claim 46).
Hirsh teaches a vial comprising the pharmaceutical formulation (p. 20; p. 198; Enumerated Embodiments 95 and 96 on p. 219; p. 224 to 225; claims 52-54 on p. 235; claim 92 on p. 239).
Hirsh further teaches a pharmaceutical composition comprising a specific formulation of:
a first SARS-CoV-2 anti-spike protein antibody or antigen-binding fragment thereof at 25-35 mg/ml;
15 mM to 25 mM, or 20 mM Na-Acetate or Na-Citrate (buffer);
6% to 10% (w/v), or 8% (w/v/) sucrose (carbohydrate) that is about 240 mM;
0.03% to 0.05% (w/v), or 0.04% (w/v) polysorbate 80 (surfactant); and
a pH of 5-6, or a pH of 5.5 (p. 20, lines 1-10; p. 197-198, p. 219, p. 225; claims 48-51).
Hirsh teaches the pharmaceutical composition comprises excipients of a buffer, surfactant, carbohydrate, an amino acid, and stabilizing agent; wherein the buffer comprises acetate, citrate, histidine or arginine; the surfactant comprises polysorbate 80; the carbohydrate comprises sucrose; the amino acid comprises arginine; and the stabilizing agent comprises arginine or amino acid (p. 196 and 198).
Hirsch teaches a pharmaceutical composition comprising a first SARS-CoV-2 anti-spike protein antibody, to be administered with a second therapeutic, wherein the second therapeutic comprises a separate pharmaceutical formulation of a second SARS-CoV-2 anti-spike protein antibody, wherein the second antibody can be antibody AZD8895 or AZD1061, or combinations thereof (p. 27, lines 32 to p. 28, line 2; p. 206; Enumerated Embodiment numbers 55-68 on p. 215-216; claims 73-91 on p. 237-239).
Hirsch further teaches a pharmaceutical composition comprising a first SARS-CoV-2 anti-spike protein antibody, to be administered with a second therapeutic, wherein the second therapeutic comprises a separate pharmaceutical formulation of a second SARS-CoV-2 anti-spike protein antibody, wherein the second antibody can be antibody AZD8895 or AZD1061, or combinations thereof (p. 27, lines 32 to p. 28, line 2; p. 206; Enumerated Embodiment numbers 55-68 on p. 215-216; claims 73-91 on p. 237-239).
Hirsh teaches kits comprising an antibody or plurality of antibodies (p. 20; Enumerated Embodiment number 70 on p. 216; p. 28, lines 4-10; p. 198; p. 216; p. 236), and teaches two separate injection vials of antibody composition, each vial containing a different antibody (p. 224-225; claims 52-53).
Hirsh teaches methods of treating or preventing COVID-19 in a subject comprising administering the pharmaceutical composition to the subject (p. 21 to 24; claims 96-98 on p. 240); wherein administration is intramuscular (p. 21-25, 32; claims 71 and 105).
Hirsch teaches methods of treating or preventing COVID-19 with the plurality of SARS-CoV-2 anti-spike protein antibodies (Enumerated Embodiment numbers 70-74 on p. 216-217; claims 96-108 on p. 240-241). Hirsh teaches methods of treating or preventing COVID-19 in a subject comprising administering a first and second SARS-CoV-2 anti-spike protein antibody pharmaceutical composition, both compositions administered intramuscularly (p. 29-33; claim 105).
Hirsch suggests the pharmaceutical composition for treating COVID-19 comprises 100 mg/ml antibody, histidine buffer, sucrose at 8% w/v (about 240 mM), about 0.04% polysorbate 80, and at a pH of 6.0 or 5.5-6.5, but does not teach:
the formulation comprises about 20 mM of histidine buffer;
the sequences of the SARS-CoV-2 anti-spike protein antibody as comprising instant SEQ ID NOs:7, 8, 17, and 18 (i.e., COV2-2196, tixagevimab, AZD8895), and/or SEQ ID NOs:15, 16, 19, and 20 (i.e., COV2-2130, cilgavimab, AZD1061) (claims 19, 20, 23-25, 30, 31, 34-36, 43);
the antibody has YTE (M252Y/S254T/T256E) and/or TM mutations (L234F/L235E/P331S) (claims 23, 24, 34, 35); and
a kit comprising the two antibodies in separate pharmaceutical compositions (claim 43).
Strickley and Lambert teach commercial SARS-CoV-2 anti-spike protein antibodies casirivimab and imdevimab for the treatment of patients with COVID-19, wherein the antibodies are formulated in separate single-dose vials, and wherein the antibodies are formulated for administration in pharmaceutical compositions at a pH 6.0 comprising:
Histidine;
Sucrose; and
Polysorbate 80; and
120 mg/ml antibody (Appendix I on p. e8; p. 2597, col. 1 “Combination administration”).
Strickley and Lambert further review known reagents and concentrations used to formulate commercially available therapeutic antibodies. Strickley and Lambert teach histidine is the most commonly used buffer to buffer formulations to a specific pH, and buffers are typically present at concentrations <50mM to minimize pain upon injections and to minimize aggregate formation. Histidine is commonly used to buffer formulations to a pH of 5.0-6.9 in commercial antibody products. The buffer concentration is most commonly between 10 mM and 20 mM. Strickley and Lambert teach other buffers are commonly used, although to a lesser extent, including citrate and acetate (p. 2592, col. 2; p. 2601, col. 1-2; Table 3; Figure 9 and 10; p. 2602, col. 1-2; Table 4 and 7).
Strickley and Lambert teach polysorbate 80 is one of the most commonly used surfactants to inhibit aggregation and to minimize surface adsorption at the air-water interface in the container and upon dilution into IV fluids (p. 2593, col. 1; p. 2603, col. 1 to p. 2605, col. 1; Appendix IV; Figure 12; Table 7).
Strickley and Lambert teach that arginine can also be formulated in antibody solutions that do not contain sucrose, and arginine can function to adjust tonicity, and be present in a range of 110 mM to 220 mM (p. 2599, col. 2; Table 7).
Strickley and Lambert teach typical antibody formulations including: histidine + sucrose + arginine + polysorbate 80 + 100 mg/mL antibody at pH 6.0 (Table 7):
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Strickley and Lambert teach casirivimab and imdevimab are commercially available in vials of pharmaceutical compositions at a concentration of 120 mg/ml comprising histidine, arginine, sucrose, polysorbate 80, at a pH of 6.0.
Crowe teaches pharmaceutical compositions comprising SARS-CoV-2 anti-spike protein antibody for the treatment of COVID-19, and they can be formulated for administration with pH buffering agents or suitable excipients including sucrose ([263-269]). Crowe teaches kits comprising first and second SARS-CoV-2 anti-spike protein antibodies for the treatment of patients with COVID-19 ([46]; [114]; [322]; claims 19, 29 and 30).
Crowe teaches SARS-CoV-2 anti-spike protein antibodies can comprise heavy chain variable region SEQ ID NO:23 and light chain variable region SEQ ID NO:24 ([27]; claims 1-2; Figure 10; COV2-2196), that are identical to instant SEQ ID Nos:7 and 8, respectively (see sequence alignments below).
Crowe teaches SARS-CoV-2 anti-spike protein antibodies can comprise heavy chain variable region SEQ ID NO:39 and light chain variable region SEQ ID No:40 ([27]; [32]; [47]; claims 1-2; COV2-2130), that are identical to instant SEQ ID NOs:15 and 16, respectively (see sequence alignments below).
Crowe demonstrates that combining COV2-2196 and COV2-2130 antibodies results in synergistic neutralizing activity on live SARS-CoV-2 virus and significantly reduced SARS-CoV-2 viral burden in a mouse model compared to single antibodies ([52]; Figure 1-4; Example 1).
Crowe teaches neutralizing SARS-CoV-2 anti-spike protein antibody AZD8895 is based on COV2-2196, AZD1061 is based on COV2-2130; and AZD7442 is the 1:1 combination of AZD1061 and AZD8895 ([63]; [366]; Fig. 11).
Crowe teaches the SARS-CoV-2 anti-spike protein antibody can comprise Fc mutations to increase half-life or therapeutic efficacy, such as the YTE mutation ([9-10]; [12]; claim 5).
Crowe teaches intramuscular administration of the antibody compositions ([267]) and methods for treating for preventing SARS-CoV-2 by administering the antibodies ([263-269]).
Capon teaches pharmaceutical compositions comprising a therapeutically effective amount of SARS-CoV-2 anti-spike protein antibody for the treatment of COVID-19, wherein the compositions can be formulated with buffers, carbohydrates including sucrose, and other stabilizers and excipients ([665-668]; [670]). Capon teaches kits comprising the pharmaceutical compositions ([597]). Capon teaches the aqueous or injectable liquid solutions of antibody are suitable for intramuscular administration ([666-668]); and are administered for treatment or prophylaxis of SARS-Cov-2 ([670]; Examples 17 and 18).
Capon teaches the sequences of known neutralizing SARS-CoV-2 anti-spike protein antibodies used in their experiments, including:
tixagevimab (AZD8895) comprising both YTE and TM mutations (Table 27; Example 11), wherein the light chain comprises SEQ ID NO:453 that is identical to instant SEQ ID NO:18, and and the heavy chain comprises SEQ ID NO:454, that is identical to amino acids 1-452 of instant SEQ ID NO:17 (see sequence alignments below); and wherein SEQ ID NO:454 comprises 100% of instant SEQ ID NO:7; and SEQ ID NO:453 comprises 100% of instant SEQ ID NO:8;
cilgavimab (AZD1061) comprising both YTE and TM mutations (Table 27; Example 11), wherein the light chain comprises SEQ ID NO:449 that is 100% identical to instant SEQ ID NO:20, the heavy chain comprises SEQ ID NO:450 that is 100% identical to amino acids 1-460 of instant SEQ ID NO:19 (see sequence alignments below); and wherein SEQ ID NO:450 comprises 100% of instant SEQ ID NO:15; and SEQ ID NO:449 comprises 100% of instant SEQ ID NO:16 (see sequence alignments below).
Capon teaches:
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193
482
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346
680
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Capon further demonstrates combining the cilgavimab and tixagevimab antibody sequences into a single multivalent antibody to neutralize SARS-COV-2 (Tables 30-31; Example 12).
Composition comprises: buffer of about 20 mM of histidine instead of citrate or acetate, and at pH of 6.0;
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to substitute in 20 mM of histidine for the 20 mM of citrate or acetate buffer taught in the composition of Hirsh. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Hirsh suggests histidine can be used as a buffer and that it serves the same buffering function as citrate and acetate (functional equivalent) and teaches providing compositions at around pH 6.0 including 6.0; (2) Strickley and Lambert teach histidine is the most commonly used buffer, and to buffer the composition to a pH of 6; (3) Strickley and Lambert suggest a typical antibody formulation including: histidine + sucrose + arginine + polysorbate 80 + 100 mg/mL antibody at pH 6.0; (4) Strickley and Lambert teach histidine is already used as a buffer in commercial SARS-CoV-2 anti-spike protein antibodies casirivimab and imdevimab; and (5) Strickley and Lambert teach histidine is commonly present at a concentration of 20 mM, and kept at a low concentration to avoid harming patients.
Composition comprises about 100 mg/ml of antibody, and at pH 6.0:
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to provide the SARS-CoV-2 anti-spike protein antibody at a concentration of about 100 mg/ml and at pH of 6.0 in the composition of Hirsh. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Hirsh suggests providing the antibody at a concentration of 100 mg/mL and pH 6.0 in the pharmaceutical composition; (2) Strickley and Lambert suggest a typical antibody formulation including: histidine + sucrose + arginine + polysorbate 80 + 100 mg/mL antibody at pH 6.0; (3) Strickley and Lambert demonstrate SARS-CoV-2 anti-spike protein antibodies casirivimab and imdevimab are commercially available in vials of pharmaceutical compositions at a concentration of 100 mg/ml comprising histidine, arginine, sucrose, polysorbate 80, at a pH of 6.0; and (4) Strickley and Lambert demonstrate therapeutic antibodies present at a variety of high concentrations around 100 mg/ml in commercial compositions and at a pH of 6.0. Given these disclosures, it is well within the level of the skilled artisan to arrive at a concentration of antibody in the composition at about 100 mg/ml at pH 6.0 and for the antibody and composition to predictably perform the same function.
Given the known and established functions of each of the claimed reagents in the pharmaceutical composition of Hirsh for stable storage and administration of SARS-CoV-2 anti-spike protein antibody, that are: (1) histidine as a buffer; (2) sucrose as a carbohydrate; (3) polysorbate 80 as surfactant; and a pH of 6.0 or about 6.0; and given the prior art teaches the known amounts of these agents successfully utilized for stable storage and administration of SARS-CoV-2 anti-spike protein antibody and the known commercial antibody compositions comprising various combinations of: 100 mg/ml antibody, 20mM histidine to buffer the formulation to pH 6.0, about 240 mM sucrose; and 0.04% (w/v) polysorbate 80, it is well within the level of the ordinary skilled artisan to formulate the antibody composition of Hirsh comprising these reagents at these amounts with a reasonable expectation of success.
SARS-COV-2 anti-spike protein antibodies comprise sequences of instant SEQ ID NOs:7+8, 15+16, 17+18, and/or 19+20, and comprise YTE/TM mutations:
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to formulate the SARS-CoV-2 anti-spike protein antibodies of Crowe or Capon in the pharmaceutical composition of the combined references. One would have been motivated to, and have a reasonable expectation of success to, because: (1) the Hirsh and Strickley and Lambert teach formulating the pharmaceutical compositions for SARS-CoV-2 anti-spike protein antibodies for therapeutic use; (2) Hirsh directly suggests therapeutic pharmaceutical compositions comprising SARS-CoV-2 anti-spike protein antibody, AZD8895, AZD1061, or combinations thereof; (3) Crowe teaches pharmaceutical compositions comprising SARS-CoV-2 anti-spike protein antibodies COV2-2196 and/or COV2-2130 antibodies comprising instant SEQ ID NOs:7+8 and 15+16, respectively, and suggests introducing YTE mutation to increase half-life and efficacy; (4) Capon teaches pharmaceutical compositions comprising antibodies AZD8895, AZD1061, or combinations thereof, further teaching antibodies AZD8895 and AZD1061 comprise TME and YTE mutations, and are derived from antibodies COV2-2169 and COV2-2130, respectively; and (5) Capon teaches the known heavy and light chain sequences of AZD8895 and AZD1061 comprising instant SEQ ID NOs:7+8; 15+16; aa 1-452 of SEQ ID NO:17, SEQ ID NO:18; aa 1-460 of SEQ ID NO:19; and SEQ ID NO:20; and methods for manipulating the sequences to make SARS-CoV-2 antibodies for pharmaceutical use.
Kit comprising two pharmaceutical compositions of the SARS-COV-2 anti-spike protein antibodies:
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to provide a kit comprising two separate pharmaceutical formulations of two antibodies (COV2-2169 + COV2-2130) or cilgavimab (AZD1061) + tixagevimab (AZD8895) in the kit of the combined references. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Hirsh and Strickley and Lambert teach kits comprising more than one pharmaceutical composition of SARS-CoV-2 anti-spike protein antibodies for the treatment of COVID-19; (2) Strickley and Lambert teach known commercially available separate pharmaceutical compositions of SARS-CoV-2 anti-spike protein antibodies used together for the treatment of COVID-19; (3) Hirsh directly suggests therapeutic pharmaceutical compositions comprising SARS-CoV-2 anti-spike protein antibody, AZD8895, AZD1061, or combinations thereof, and kits comprising a plurality of antibodies; (4) Crowe demonstrates that combining COV2-2196 and COV2-2130 antibodies results in synergistic neutralizing activity on live SARS-CoV-2 virus and significantly reduced SARS-CoV-2 viral burden in a mouse model compared to single antibodies; (4) Capon teaches AZD8895 and AZD1061 antibodies and kits comprising pharmaceutical compositions of their disclosed antibodies; (5) Capon demonstrates combining the heavy and light chain sequences of AZD8895 and AZD1061 antibodies to produce multivalent SARS-CoV-2 anti-spike antibodies for therapeutic use.
The cited prior art: (1) teaches the known antibody sequences of COV2-2169 + COV2-2130, or cilgavimab (AZD1061) + tixagevimab (AZD8895), their neutralizing activity, and their use in the treatment of COVID-19, (2) teaches pharmaceutical compositions and kits to comprise multiple SARS-CoV-2 anti-spike antibodies, and the known commercial use of separate SARS-CoV-2 anti-spike antibody pharmaceutical compositions together to treat COVID-19; (3) teaches known synergistic treatment effects of combining the COV2-2169 + COV2-2130 antibodies together, from which AZD8895 and AZD1061 antibodies are derived; and (4) teach bringing together the sequences of AZD8895 and AZD1061 antibodies to produce multivalent SARS-CoV-2 anti-spike antibodies for therapeutic use. Thus, the cited prior art provides both motivation and reasonable expectation of success to bring together the two antibodies, COV2-2169 + COV2-2130 or AZD8895 + AZD1061, or pharmaceutical compositions comprising each antibody; for use in the treatment of COVID-19 and to produce a kit comprising both compositions.
Instant SEQ ID NO:7 aligned with Crowe SEQ ID NO:23 (VH of COV2-2169):
RESULT 1
US-17-212-949-23
Sequence 23, US/17212949
Publication No. US20210300999A1
GENERAL INFORMATION
APPLICANT: Vanderbilt University
APPLICANT: Crowe, James E Jr.
APPLICANT: Zost, Seth
APPLICANT: Carnahan, Robert
APPLICANT: Gilchuk, Pavlo
TITLE OF INVENTION: Human Monoclonal Antibodies to Severe Acute Respiratory Syndrome
TITLE OF INVENTION: Corona Virus 2 (SARS-CoV-2)
FILE REFERENCE: 4815.001000C
CURRENT APPLICATION NUMBER: US/17/212,949
CURRENT FILING DATE: 2021-03-25
PRIOR APPLICATION NUMBER: US 63/000,299
PRIOR FILING DATE: 2020-03-26
PRIOR APPLICATION NUMBER: US 63/002,896
PRIOR FILING DATE: 2020-03-31
PRIOR APPLICATION NUMBER: US 63/003,716
PRIOR FILING DATE: 2020-04-01
PRIOR APPLICATION NUMBER: US 63/023,545
PRIOR FILING DATE: 2020-05-12
PRIOR APPLICATION NUMBER: US 63/024,204
PRIOR FILING DATE: 2020-05-13
PRIOR APPLICATION NUMBER: US 63/024,248
PRIOR FILING DATE: 2020-05-13
PRIOR APPLICATION NUMBER: US 63/027,173
PRIOR FILING DATE: 2020-05-19
PRIOR APPLICATION NUMBER: US 63/037,984
PRIOR FILING DATE: 2020-06-11
PRIOR APPLICATION NUMBER: US 63/040,224
PRIOR FILING DATE: 2020-06-17
PRIOR APPLICATION NUMBER: US 63/040,246
PRIOR FILING DATE: 2020-06-17
Remaining Prior Application data removed - See File Wrapper or PALM.
NUMBER OF SEQ ID NOS: 187
SEQ ID NO 23
LENGTH: 123
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: COV2-2838 heavy
Query Match 100.0%; Score 646; Length 123;
Best Local Similarity 100.0%;
Matches 123; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QMQLVQSGPEVKKPGTSVKVSCKASGFTFMSSAVQWVRQARGQRLEWIGWIVIGSGNTNY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QMQLVQSGPEVKKPGTSVKVSCKASGFTFMSSAVQWVRQARGQRLEWIGWIVIGSGNTNY 60
Qy 61 AQKFQERVTITRDMSTSTAYMELSSLRSEDTAVYYCAAPYCSSISCNDGFDIWGQGTMVT120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AQKFQERVTITRDMSTSTAYMELSSLRSEDTAVYYCAAPYCSSISCNDGFDIWGQGTMVT120
Qy 121 VSS 123
|||
Db 121 VSS 123
Instant SEQ ID NO:8 aligned with Crowe SEQ ID NO:24 (VL of COV2-2169):
RESULT 1
US-17-212-949-24
Sequence 24, US/17212949
Publication No. US20210300999A1
GENERAL INFORMATION
APPLICANT: Vanderbilt University
APPLICANT: Crowe, James E Jr.
APPLICANT: Zost, Seth
APPLICANT: Carnahan, Robert
APPLICANT: Gilchuk, Pavlo
TITLE OF INVENTION: Human Monoclonal Antibodies to Severe Acute Respiratory Syndrome
TITLE OF INVENTION: Corona Virus 2 (SARS-CoV-2)
FILE REFERENCE: 4815.001000C
CURRENT APPLICATION NUMBER: US/17/212,949
CURRENT FILING DATE: 2021-03-25
PRIOR APPLICATION NUMBER: US 63/000,299
PRIOR FILING DATE: 2020-03-26
PRIOR APPLICATION NUMBER: US 63/002,896
PRIOR FILING DATE: 2020-03-31
PRIOR APPLICATION NUMBER: US 63/003,716
PRIOR FILING DATE: 2020-04-01
PRIOR APPLICATION NUMBER: US 63/023,545
PRIOR FILING DATE: 2020-05-12
PRIOR APPLICATION NUMBER: US 63/024,204
PRIOR FILING DATE: 2020-05-13
PRIOR APPLICATION NUMBER: US 63/024,248
PRIOR FILING DATE: 2020-05-13
PRIOR APPLICATION NUMBER: US 63/027,173
PRIOR FILING DATE: 2020-05-19
PRIOR APPLICATION NUMBER: US 63/037,984
PRIOR FILING DATE: 2020-06-11
PRIOR APPLICATION NUMBER: US 63/040,224
PRIOR FILING DATE: 2020-06-17
PRIOR APPLICATION NUMBER: US 63/040,246
PRIOR FILING DATE: 2020-06-17
Remaining Prior Application data removed - See File Wrapper or PALM.
NUMBER OF SEQ ID NOS: 187
SEQ ID NO 24
LENGTH: 109
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: COV2-2838 light
Query Match 100.0%; Score 569; Length 109;
Best Local Similarity 100.0%;
Matches 109; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIP 60
Qy 61 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGSSRGWTFGQGTKVEIK 109
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGSSRGWTFGQGTKVEIK 109
Instant SEQ ID NO:15 aligned with Crowe SEQ ID NO:39 (VH of COV2-2130):
RESULT 1
US-17-212-949-39
Sequence 39, US/17212949
Publication No. US20210300999A1
GENERAL INFORMATION
APPLICANT: Vanderbilt University
APPLICANT: Crowe, James E Jr.
APPLICANT: Zost, Seth
APPLICANT: Carnahan, Robert
APPLICANT: Gilchuk, Pavlo
TITLE OF INVENTION: Human Monoclonal Antibodies to Severe Acute Respiratory Syndrome
TITLE OF INVENTION: Corona Virus 2 (SARS-CoV-2)
FILE REFERENCE: 4815.001000C
CURRENT APPLICATION NUMBER: US/17/212,949
CURRENT FILING DATE: 2021-03-25
PRIOR APPLICATION NUMBER: US 63/000,299
PRIOR FILING DATE: 2020-03-26
PRIOR APPLICATION NUMBER: US 63/002,896
PRIOR FILING DATE: 2020-03-31
PRIOR APPLICATION NUMBER: US 63/003,716
PRIOR FILING DATE: 2020-04-01
PRIOR APPLICATION NUMBER: US 63/023,545
PRIOR FILING DATE: 2020-05-12
PRIOR APPLICATION NUMBER: US 63/024,204
PRIOR FILING DATE: 2020-05-13
PRIOR APPLICATION NUMBER: US 63/024,248
PRIOR FILING DATE: 2020-05-13
PRIOR APPLICATION NUMBER: US 63/027,173
PRIOR FILING DATE: 2020-05-19
PRIOR APPLICATION NUMBER: US 63/037,984
PRIOR FILING DATE: 2020-06-11
PRIOR APPLICATION NUMBER: US 63/040,224
PRIOR FILING DATE: 2020-06-17
PRIOR APPLICATION NUMBER: US 63/040,246
PRIOR FILING DATE: 2020-06-17
Remaining Prior Application data removed - See File Wrapper or PALM.
NUMBER OF SEQ ID NOS: 187
SEQ ID NO 39
LENGTH: 131
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: COV2-2130 heavy
Query Match 100.0%; Score 702; Length 131;
Best Local Similarity 100.0%;
Matches 131; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFRDVWMSWVRQAPGKGLEWVGRIKSKIDGGTT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFRDVWMSWVRQAPGKGLEWVGRIKSKIDGGTT 60
Qy 61 DYAAPVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTTAGSYYYDTVGPGLPEGKFDY120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DYAAPVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTTAGSYYYDTVGPGLPEGKFDY120
Qy 121 WGQGTLVTVSS 131
|||||||||||
Db 121 WGQGTLVTVSS 131
Instant SEQ ID NO:16 aligned with Crowe SEQ ID NO:40 (VL of COV2-2130):
RESULT 1
US-17-212-949-40
Sequence 40, US/17212949
Publication No. US20210300999A1
GENERAL INFORMATION
APPLICANT: Vanderbilt University
APPLICANT: Crowe, James E Jr.
APPLICANT: Zost, Seth
APPLICANT: Carnahan, Robert
APPLICANT: Gilchuk, Pavlo
TITLE OF INVENTION: Human Monoclonal Antibodies to Severe Acute Respiratory Syndrome
TITLE OF INVENTION: Corona Virus 2 (SARS-CoV-2)
FILE REFERENCE: 4815.001000C
CURRENT APPLICATION NUMBER: US/17/212,949
CURRENT FILING DATE: 2021-03-25
PRIOR APPLICATION NUMBER: US 63/000,299
PRIOR FILING DATE: 2020-03-26
PRIOR APPLICATION NUMBER: US 63/002,896
PRIOR FILING DATE: 2020-03-31
PRIOR APPLICATION NUMBER: US 63/003,716
PRIOR FILING DATE: 2020-04-01
PRIOR APPLICATION NUMBER: US 63/023,545
PRIOR FILING DATE: 2020-05-12
PRIOR APPLICATION NUMBER: US 63/024,204
PRIOR FILING DATE: 2020-05-13
PRIOR APPLICATION NUMBER: US 63/024,248
PRIOR FILING DATE: 2020-05-13
PRIOR APPLICATION NUMBER: US 63/027,173
PRIOR FILING DATE: 2020-05-19
PRIOR APPLICATION NUMBER: US 63/037,984
PRIOR FILING DATE: 2020-06-11
PRIOR APPLICATION NUMBER: US 63/040,224
PRIOR FILING DATE: 2020-06-17
PRIOR APPLICATION NUMBER: US 63/040,246
PRIOR FILING DATE: 2020-06-17
Remaining Prior Application data removed - See File Wrapper or PALM.
NUMBER OF SEQ ID NOS: 187
SEQ ID NO 40
LENGTH: 112
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: COV2-2130 light
Query Match 100.0%; Score 583; Length 112;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLMYWASTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLMYWASTR 60
Qy 61 ESGVPDRFSGSGSGAEFTLTISSLQAEDVAIYYCQQYYSTLTFGGGTKVEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ESGVPDRFSGSGSGAEFTLTISSLQAEDVAIYYCQQYYSTLTFGGGTKVEIK 112
Instant SEQ ID NO:17 aligned with Capon SEQ ID NO:454:
RESULT 3
US-17-373-751-454
(NOTE: this sequence has 6 duplicates in the database searched.
See complete list at the end of this report)
Sequence 454, US/17373751
Publication No. US20220025071A1
GENERAL INFORMATION
APPLICANT: Biomolecular Holdings LLC
TITLE OF INVENTION: Tetrahedral Antibodies
FILE REFERENCE: 91300-B
CURRENT APPLICATION NUMBER: US/17/373,751
CURRENT FILING DATE: 2021-07-12
PRIOR APPLICATION NUMBER: 63/050,738
PRIOR FILING DATE: 2020-07-10
NUMBER OF SEQ ID NOS: 4657
SEQ ID NO 454
LENGTH: 452
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Tixagevimab_11776_Vh-CH
Query Match 99.8%; Score 2411; Length 452;
Best Local Similarity 100.0%;
Matches 452; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QMQLVQSGPEVKKPGTSVKVSCKASGFTFMSSAVQWVRQARGQRLEWIGWIVIGSGNTNY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QMQLVQSGPEVKKPGTSVKVSCKASGFTFMSSAVQWVRQARGQRLEWIGWIVIGSGNTNY 60
Qy 61 AQKFQERVTITRDMSTSTAYMELSSLRSEDTAVYYCAAPYCSSISCNDGFDIWGQGTMVT120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AQKFQERVTITRDMSTSTAYMELSSLRSEDTAVYYCAAPYCSSISCNDGFDIWGQGTMVT120
Qy 121 VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL180
Qy 181 QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEF240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEF240
Qy 241 EGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 EGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE300
Qy 301 QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPS360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREPQVYTLPPS360
Qy 361 REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK420
Qy 421 SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 452
||||||||||||||||||||||||||||||||
Db 421 SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 452
Instant SEQ ID NO:18 aligned with Capon SEQ ID NO:453:
RESULT 1
US-17-373-751-453
Sequence 453, US/17373751
Publication No. US20220025071A1
GENERAL INFORMATION
APPLICANT: Biomolecular Holdings LLC
TITLE OF INVENTION: Tetrahedral Antibodies
FILE REFERENCE: 91300-B
CURRENT APPLICATION NUMBER: US/17/373,751
CURRENT FILING DATE: 2021-07-12
PRIOR APPLICATION NUMBER: 63/050,738
PRIOR FILING DATE: 2020-07-10
NUMBER OF SEQ ID NOS: 4657
SEQ ID NO 453
LENGTH: 216
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Tixagevimab_11776_VK-CK
Query Match 100.0%; Score 1122; Length 216;
Best Local Similarity 100.0%;
Matches 216; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIP 60
Qy 61 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGSSRGWTFGQGTKVEIKRTVAAPSVFIF120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQHYGSSRGWTFGQGTKVEIKRTVAAPSVFIF120
Qy 121 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSST180
Qy 181 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 216
||||||||||||||||||||||||||||||||||||
Db 181 LTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 216
Instant SEQ ID NO:15 aligned with Capon SEQ ID NO:450:
RESULT 7
US-17-373-751-450
Sequence 450, US/17373751
Publication No. US20220025071A1
GENERAL INFORMATION
APPLICANT: Biomolecular Holdings LLC
TITLE OF INVENTION: Tetrahedral Antibodies
FILE REFERENCE: 91300-B
CURRENT APPLICATION NUMBER: US/17/373,751
CURRENT FILING DATE: 2021-07-12
PRIOR APPLICATION NUMBER: 63/050,738
PRIOR FILING DATE: 2020-07-10
NUMBER OF SEQ ID NOS: 4657
SEQ ID NO 450
LENGTH: 460
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Cilgavimab_11777_VH-CH
Query Match 100.0%; Score 702; Length 460;
Best Local Similarity 100.0%;
Matches 131; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFRDVWMSWVRQAPGKGLEWVGRIKSKIDGGTT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFRDVWMSWVRQAPGKGLEWVGRIKSKIDGGTT 60
Qy 61 DYAAPVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTTAGSYYYDTVGPGLPEGKFDY120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DYAAPVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTTAGSYYYDTVGPGLPEGKFDY120
Qy 121 WGQGTLVTVSS 131
|||||||||||
Db 121 WGQGTLVTVSS 131
Instant SEQ ID NO:16 aligned with Capon SEQ ID NO:449:
RESULT 4
US-17-373-751-449
Sequence 449, US/17373751
Publication No. US20220025071A1
GENERAL INFORMATION
APPLICANT: Biomolecular Holdings LLC
TITLE OF INVENTION: Tetrahedral Antibodies
FILE REFERENCE: 91300-B
CURRENT APPLICATION NUMBER: US/17/373,751
CURRENT FILING DATE: 2021-07-12
PRIOR APPLICATION NUMBER: 63/050,738
PRIOR FILING DATE: 2020-07-10
NUMBER OF SEQ ID NOS: 4657
SEQ ID NO 449
LENGTH: 219
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Cilgavimab_11777_VK-CK
Query Match 100.0%; Score 583; Length 219;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLMYWASTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLMYWASTR 60
Qy 61 ESGVPDRFSGSGSGAEFTLTISSLQAEDVAIYYCQQYYSTLTFGGGTKVEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ESGVPDRFSGSGSGAEFTLTISSLQAEDVAIYYCQQYYSTLTFGGGTKVEIK 112
Instant SEQ ID NO:19 aligned with Capon SEQ ID NO:450:
RESULT 3
US-17-373-751-450
(NOTE: this sequence has 6 duplicates in the database searched.
See complete list at the end of this report)
Sequence 450, US/17373751
Publication No. US20220025071A1
GENERAL INFORMATION
APPLICANT: Biomolecular Holdings LLC
TITLE OF INVENTION: Tetrahedral Antibodies
FILE REFERENCE: 91300-B
CURRENT APPLICATION NUMBER: US/17/373,751
CURRENT FILING DATE: 2021-07-12
PRIOR APPLICATION NUMBER: 63/050,738
PRIOR FILING DATE: 2020-07-10
NUMBER OF SEQ ID NOS: 4657
SEQ ID NO 450
LENGTH: 460
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Cilgavimab_11777_VH-CH
Query Match 99.8%; Score 2467; Length 460;
Best Local Similarity 100.0%;
Matches 460; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFRDVWMSWVRQAPGKGLEWVGRIKSKIDGGTT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVKPGGSLRLSCAASGFTFRDVWMSWVRQAPGKGLEWVGRIKSKIDGGTT 60
Qy 61 DYAAPVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTTAGSYYYDTVGPGLPEGKFDY120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DYAAPVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCTTAGSYYYDTVGPGLPEGKFDY120
Qy 121 WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSG180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSG180
Qy 181 VHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTC240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTC240
Qy 241 PPCPAPEFEGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PPCPAPEFEGGPSVFLFPPKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN300
Qy 301 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREP360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPASIEKTISKAKGQPREP360
Qy 361 QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 QVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFL420
Qy 421 YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 460
||||||||||||||||||||||||||||||||||||||||
Db 421 YSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 460
Instant SEQ ID NO:20 aligned with Capon SEQ ID NO:449:
RESULT 1
US-17-373-751-449
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
Sequence 449, US/17373751
Publication No. US20220025071A1
GENERAL INFORMATION
APPLICANT: Biomolecular Holdings LLC
TITLE OF INVENTION: Tetrahedral Antibodies
FILE REFERENCE: 91300-B
CURRENT APPLICATION NUMBER: US/17/373,751
CURRENT FILING DATE: 2021-07-12
PRIOR APPLICATION NUMBER: 63/050,738
PRIOR FILING DATE: 2020-07-10
NUMBER OF SEQ ID NOS: 4657
SEQ ID NO 449
LENGTH: 219
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Cilgavimab_11777_VK-CK
Query Match 100.0%; Score 1136; Length 219;
Best Local Similarity 100.0%;
Matches 219; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLMYWASTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLAWYQQKPGQPPKLLMYWASTR 60
Qy 61 ESGVPDRFSGSGSGAEFTLTISSLQAEDVAIYYCQQYYSTLTFGGGTKVEIKRTVAAPSV120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ESGVPDRFSGSGSGAEFTLTISSLQAEDVAIYYCQQYYSTLTFGGGTKVEIKRTVAAPSV120
Qy 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL180
Qy 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
|||||||||||||||||||||||||||||||||||||||
Db 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
Response to Relevant Arguments
4. Applicants argue that Examiner combined diverse and unrelated portions of four different references without any reason why one would select the precise components in the precise amounts required by the present claims. Applicants argue that Hirsh does not teach the specific combination of antibody, histidine, arginine or sucrose, polysorbate 80 and at a pH of 5.5-6.5. Applicants argue that Hirsh does not teach formulating histidine at 20 mM. Applicants argue the exemplary formulations disclosed by Hirsh only comprise 25 to 35 mg/ml antibody and not 100 mg/ml antibody as claimed.
Applicants argue that Strickley and Lambert do not remedy these deficiencies. Applicants argue the claims are also amended to recite an intended use of intramuscular injection for the composition, and a step of intramuscular injection for the methods. Applicants argue that Strickley and Lambert teach intramuscular route of injection but exclude sucrose and polysorbate. Applicants argue that Strickley and Lambert do not teach using 20 mM histidine in a formulation of intramuscular injection.
5. The arguments have been carefully considered but are not persuasive. Hirsh does teach and suggest a pharmaceutical composition comprising 100 mg/mL SARS-CoV-2 anti-spike antibody, histidine buffer, amino acid arginine, sucrose carbohydrate, polysorbate 80 surfactant, and at a pH of 5.5-6.5 or about 6.0, that is formulated for intramuscular administration, therefore these are not deficiencies:
Hirsh p. 19:
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media_image4.png
752
866
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Hirsh p. 218-219:
PNG
media_image5.png
170
806
media_image5.png
Greyscale
PNG
media_image6.png
644
814
media_image6.png
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Contrary to arguments, Hirsh teaches formulating the antibody compositions with precise amounts of sucrose at about 240 mM (8% w/v sucrose) and polysorbate 80 at 0.04% (w/v):
Hirsh p. 20:
PNG
media_image7.png
338
796
media_image7.png
Greyscale
Hirsh p. 219:
PNG
media_image8.png
262
804
media_image8.png
Greyscale
Hirsh p. 225:
PNG
media_image9.png
338
796
media_image9.png
Greyscale
Substituting the functionally equivalent 20 mM histidine buffer of Strickley and Lambert for the 20mM Na-Citrate buffer of Hirsh to achieve a pH of 6.0, and increasing the amount of antibody to 100 mg/ml in the composition as suggested by Hirsh, were addressed by Strickley and Lambert for the reasons of record in the obviousness rationale of the rejection. See MPEP 2144.06 regarding functional equivalents.
Given the known and established functions of each of the claimed reagents in the pharmaceutical composition of Hirsh for stable storage and IM administration of SARS-CoV-2 anti-spike protein antibody, that are: (1) histidine as a buffer; (2) sucrose as a carbohydrate; (3) polysorbate 80 as surfactant; and a pH of 6.0 or about 6.0; and given the prior art teaches the known amounts of these agents successfully utilized for stable storage and administration of SARS-CoV-2 anti-spike protein antibody and the known commercial antibody compositions comprising various combinations of: 100 mg/ml antibody, 20mM histidine to buffer the formulation to pH 6.0, about 240 mM sucrose; and 0.04% (w/v) polysorbate 80, it is well within the level of the ordinary skilled artisan to formulate the antibody composition of Hirsh comprising these reagents at these amounts, and to administer them intramuscularly with a reasonable expectation of success.
Applicant’s arguments that Strickley and Lambert exclude histidine and sucrose from formulations for intramuscular (IM) administration on p. 2597 are not persuasive. In the “Intramuscular” paragraph on p. 2597, Strickley and Lambert mention one commercial antibody, SYNAGIS®, approved for IM administration and its formulation with 100 mg/ml antibody, glycine, histidine 0.025M buffer, and pH 6. This paragraph does not teach away from or discourage adding 20 mM histidine and 240 mM sucrose to the antibody formulation taught by Hirsh and Strickley and Lambert, but rather, demonstrates and supports motivation for combining 100 mg/ml antibody with histidine buffer for IM administration for the composition and methods taught by Hirsh.
Contrary to arguments, Examiner did not piece together irrelevant references or irrelevant sections from references to demonstrate obviousness. The cited references are analogous art teaching known formulations of pharmaceutical compositions of antibodies, particularly for stable antibody storage, pharmaceutical administration, and treating/prophylaxis of COVID-19.
6. Applicants argue that Crowe and Capon do not cure the deficiencies of Hirsh and Strickley argued above.
7. The arguments have been carefully considered but are not persuasive because Hirsh and Strickley do not have the deficiencies argued, therefore Crowe and Capon do not need to remedy them. Further, Crowe and Capon, like Hirsh, suggest administering their antibodies intramuscularly to treat COVID-19. Crowe and Capon render obvious substituting their SARS-CoV-2 anti-spike protein antibodies into the compositions and methods of Hirsh, for the reasons of record.
8. All other objections rejections recited in the Office Action mailed November 4, 2025 are hereby withdrawn in view of amendments. The rejections under 35 USC 102 are all withdrawn in view of claim amendments requiring specific antibody sequences that Hirsh and Strickley and Lambert do not teach. The rejection under 35 USC 103 as being obvious over WO 2022/026592, Hirsh in view of Strickley and Lambert is withdrawn in view of claim amendments requiring specific antibody sequences that Hirsh and Strickley and Lambert do not teach. The previous rejection under 35 USC 103 as being obvious over WO 2022/026592, Hirsh and Strickley and Lambert in view of Crowe and Capon is withdrawn in view of claim amendments and new claims requiring new limitations of specific antibody sequences, 100 mg/ml antibody, and intramuscular injection that were not previously addressed in the rejections.
9. Conclusion: No claim is allowed.
Conclusion
10. 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.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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, Samira Jean-Louis can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Laura B Goddard/Primary Examiner, Art Unit 1642
Prosecution Insights