DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments and Arguments
2. The Miscellaneous Action (PTO-90C) mailed July 7, 2026 has been withdrawn.
3. Newly submitted claims 1-4 and 6-12 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: newly amended claims 1-4 and 6-12 are drawn to a method of treating comprising administering to a human an anti-CD28 Fab' antibody fragment consisting of a heterodimer, while originally presented claims were drawn to a product, an anti-CD28 Fab' antibody fragment consisting of a heterodimer. Only claim 15 reads on the originally presented examined subject matter. Applicant has received a first action on the merits (FAOM) reading on the originally claimed invention, the product. Thus, the inventions of the pending claims (1-4 and 6-12) and invention of originally elected claim (15) are not one and the same, thus different and distinct and would have garnered a requisite restriction.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits.
Accordingly, claims 1-4 and 6-12 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the Examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
4. Claims 1-4, 6-12 and 15 are pending.
Claims 1-4 and 6-12, drawn to a non-elected invention is withdrawn from consideration.
Claims 5, 13 and 14 have been cancelled.
Claims 1-4, 6-11, 12 and 15 have been amended.
Claim 15 is examined on the merits.
Withdrawn Objections
Claim Objections
5. Claims 6-8, 12 and 15 are no longer objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claims because they have been amended to no longer have improper multiple dependency. See MPEP § 608.01(n). Claims 5 and 13 have been cancelled.
6. Claim 4 is no longer objected to because line 3 of the claim properly recites “…0.5mg/kg to once…”, see Amendments to the Claims submitted October 23, 2025.
Withdrawn Grounds of Rejection
Claim Rejections - 35 USC § 103
7. The rejection of claim(s) 1-4 and 9-11 under 35 U.S.C. 103 as being unpatentable over Mary et al., WO 2011/101791 A1 (published 25 August 2011/ IDS reference, Foreign Patent Document #1 submitted September 8, 2023) is withdrawn as the amended claims no longer read on the original presented subject matter. Claim 14 has been cancelled.
8. The rejection of claim(s) 1-4 and 9-11 under 35 U.S.C. 103 as being unpatentable over Mary et al., US 8,785,604 B2 (published July 22, 2014/ IDS reference, U.S.Patents Document #1 submitted September 8, 2023) is withdrawn as the amended claims no longer read on the original presented subject matter. Claim 14 has been cancelled.
New Objections
Claim Objections
9. Claim 15 is objected to because of the following informality: the claim depends on a non-examined claim.
Correction is required.
New Grounds of Rejection
Claim Rejections - 35 USC § 102
10. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
11. Claim(s) 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mary et al., WO 2011/101791 A1 (published 25 August 2011/ IDS reference, Foreign Patent Document #1 submitted September 8, 2023). Mary discloses “…recombinant antibodies comprising a CD28-binding site associate with one or more heterologous polypeptide(s).”, see page 4, lines 6 and 7. The recombinant Fab’ fragment contains a heavy chain that is sequence 4 and a light chain that is sequence 6, see page 4, lines 12-14. Mary’s sequence 4 is the same as Applicant’s SEQ ID NO: 1 and sequence 6 is the same as Applicant’s SEQ ID NO: 2, see sequence alignments on the following pages.
The disclosed therapeutic composition comprises the said CD28 Fab’ antibody with a pharmaceutically acceptable excipient and “formulated at a dose of from 0.5 to 20 mg/Kg,”, see page 7, lines 1-6. This composition is suitable for parenteral administration, as well as sub-cutaneous or intra-venous injection, see page 7, lines 3-6. It is art known an injection is implemented via a medical device, a syringe to deliver a composition. Absent evidence to the contrary, the prior art reads on a syringe to deliver the injection of the disclosed composition.
RESULT 1 from 1.rag database.
AZM49080
ID AZM49080 standard; protein; 231 AA.
XX
DT 13-OCT-2011 (first entry)
XX
DE Anti-CD28 antibody heavy chain region.
XX
KW CD28; T cell surface glycoprotein CD28; allergy; antiallergic;
KW antibody therapy; antiinflammatory; autoimmune disease;
KW chronic inflammation; graft versus host disease; heavy chain;
KW humanized antibody; hypertension; hypotensive; immunosuppressive; mutein;
KW therapeutic; transplant rejection; vascular disease.
XX
OS Homo sapiens.
OS Mus sp.
OS Chimeric.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Region 1..120
FT /label= Anti-CD28_variable_heavy_chain
FT Misc-difference 11
FT /note= "Wild-type Val substituted by Lys"
FT Misc-difference 18
FT /note= "Wild-type Arg substituted by Lys"
FT Misc-difference 19
FT /note= "Wild-type Leu substituted by Val"
FT Region 29..32
FT /label= Complementarity_determining_region_1
FT Region 47..63
FT /label= Complementarity_determining_region_2
FT Misc-difference 62
FT /note= "Wild-type Lys substituted by Gln"
FT Misc-difference 87
FT /note= "Wild-type Ser substituted by Pro"
FT Region 96..108
FT /label= Complementarity_determining_region_3
FT Region 121..211
FT /label= Human_CH1
XX
CC PN WO2011101791-A1.
XX
CC PD 25-AUG-2011.
XX
CC PF 16-FEB-2011; 2011WO-IB050646.
XX
PR 18-FEB-2010; 2010EP-00290080.
PR 13-JUL-2010; 2010EP-00290389.
XX
CC PA (TCLP-) TCL PHARMA.
CC PA (INRM ) INSERM INST NAT SANTE&RECH MEDICALE.
XX
CC PI Mary C, Poirier N, Vanhove B;
XX
DR WPI; 2011-K92195/58.
DR N-PSDB; AZM49065.
XX
CC PT New anti-CD28 antibody, useful for preparing therapeutic composition for
CC PT treating a pathological condition selected from transplant rejection,
CC PT chronic allograft vasculopathy, graft-versus-host disease, and
CC PT hypertension.
XX
CC PS Claim 3; Page; 35pp; English.
XX
CC The present invention relates to a novel anti-CD28 antibody and its
CC therapeutic uses. The invention also provides a therapeutic composition
CC comprising the antibody. The antibody used in the invention is useful for
CC treating a pathological condition selected from transplant rejection,
CC chronic allograft vasculopathy, graft-versus-host disease, T-lymphocyte-
CC mediated autoimmune diseases, hypertension, allergic phenomena and
CC chronic inflammatory diseases. The present sequence is a specifically
CC claimed anti-CD28 antibody heavy chain region which comprises an anti-CD8
CC humanized antibody VH region, and a human CH1 region (accession number:
CC AAF03881) used in the invention. Note: The present sequence is not shown
CC in the specification, but is a claimed fragment of an anti-CD28 antibody
CC heavy chain given in the sequence listing (seeAZM49066).
XX
SQ Sequence 231 AA;
Query Match 100.0%; Score 1221; Length 231;
Best Local Similarity 100.0%;
Matches 231; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 60
Qy 62 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 120
Qy 122 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 182 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 232
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 231
RESULT 4 from 1.rng database.
AZM49066
ID AZM49066 standard; protein; 251 AA.
XX
DT 13-OCT-2011 (first entry)
XX
DE Anti-CD28 antibody heavy chain region, SEQ ID 4.
XX
KW CD28; T cell surface glycoprotein CD28; allergy; antiallergic;
KW antibody therapy; antiinflammatory; autoimmune disease;
KW chronic inflammation; graft versus host disease; heavy chain;
KW humanized antibody; hypertension; hypotensive; immunosuppressive; mutein;
KW therapeutic; transplant rejection; vascular disease.
XX
OS Homo sapiens.
OS Mus sp.
OS Chimeric.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Peptide 1..20
FT /label= Murine_CD28.3_antibody_variable_heavy_chain_signa
FT l_peptide
FT Region 21..140
FT /label= Anti-CD28_variable_heavy_chain
FT Misc-difference 31
FT /note= "Wild-type Val substituted by Lys"
FT Misc-difference 38
FT /note= "Wild-type Arg substituted by Lys"
FT Misc-difference 39
FT /note= "Wild-type Leu substituted by Val"
FT Region 49..52
FT /label= Complementarity_determining_region_1
FT Region 67..83
FT /label= Complementarity_determining_region_2
FT Misc-difference 82
FT /note= "Wild-type Lys substituted by Gln"
FT Misc-difference 107
FT /note= "Wild-type Ser substituted by Pro"
FT Region 116..128
FT /label= Complementarity_determining_region_3
FT Region 141..251
FT /label= Human_CH1
XX
CC PN WO2011101791-A1.
XX
CC PD 25-AUG-2011.
XX
XX
CC PI Mary C, Poirier N, Vanhove B;
XX
DR WPI; 2011-K92195/58.
DR N-PSDB; AZM49065.
XX
CC PT New anti-CD28 antibody, useful for preparing therapeutic composition for
CC PT treating a pathological condition selected from transplant rejection,
CC PT chronic allograft vasculopathy, graft-versus-host disease, and
CC PT hypertension.
XX
CC PS Example 1; SEQ ID NO 4; 35pp; English.
XX
CC The present invention relates to a novel anti-CD28 antibody and its
CC therapeutic uses. The invention also provides a therapeutic composition
CC comprising the antibody. The antibody used in the invention is useful for
CC treating a pathological condition selected from transplant rejection,
CC chronic allograft vasculopathy, graft-versus-host disease, T-lymphocyte-
CC mediated autoimmune diseases, hypertension, allergic phenomena and
CC chronic inflammatory diseases. The present sequence is an anti-CD28
CC antibody heavy chain region which comprises an anti-CD8 humanized
CC antibody VH region, a human CH1 region (accession number: AAF03881) and a
CC native murine CD28.3 antibody heavy chain leader peptide used in an
CC exemplification of the invention. Note: The present sequence is described
CC as SEQ ID NO:4 in the sequence listing , but it differs from the sequence
CC given as SEQ ID NO:4 in claim 5 (seeAZM49070).
XX
SQ Sequence 251 AA;
Query Match 100.0%; Score 1221; Length 251;
Best Local Similarity 100.0%;
Matches 231; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 80
Qy 62 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 140
Qy 122 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 200
Qy 182 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 232
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 201 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 251
RESULT 1 from 2.rng database.
AZM49081
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID AZM49081 standard; protein; 214 AA.
XX
DT 13-OCT-2011 (first entry)
XX
DE Anti-CD28 antibody light chain region.
XX
KW CD28; T cell surface glycoprotein CD28; allergy; antiallergic;
KW antibody therapy; antiinflammatory; autoimmune disease;
KW chronic inflammation; graft versus host disease; humanized antibody;
KW hypertension; hypotensive; immunosuppressive; light chain; mutein;
KW therapeutic; transplant rejection; vascular disease.
XX
OS Mus sp.
OS Homo sapiens.
OS Chimeric.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Region 1..108
FT /label= Anti-CD28_variable_light_chain
FT Misc-difference 9
FT /note= "Mutation occurred site"
FT Misc-difference 13
FT /note= "Mutation occurred site"
FT Misc-difference 17
FT /note= "Mutation occurred site"
FT Misc-difference 18
FT /note= "Mutation occurred site"
FT Misc-difference 24
FT /note= "Mutation occurred site"
FT Region 32..39
FT /label= Complementarity_determining_region_1
FT Misc-difference 40
FT /note= "Mutation occurred site"
FT Region 50..57
FT /label= Complementarity_determining_region_2
FT Misc-difference 74
FT /note= "Mutation occurred site"
FT Misc-difference 76
FT /note= "Mutation occurred site"
FT Misc-difference 80
FT /note= "Mutation occurred site"
FT Region 90..96
FT /label= Complementarity_determining_region_3
FT Misc-difference 96
FT /label= Cys, Ala, Asn
FT Region 109..194
FT /label= Human_c_kappa_region
XX
CC PN WO2011101791-A1.
XX
CC PD 25-AUG-2011.
XX
CC PI Mary C, Poirier N, Vanhove B;
XX
DR WPI; 2011-K92195/58.
DR N-PSDB; AZM49067.
XX
CC PT New anti-CD28 antibody, useful for preparing therapeutic composition for
CC PT treating a pathological condition selected from transplant rejection,
CC PT chronic allograft vasculopathy, graft-versus-host disease, and
CC PT hypertension.
XX
CC PS Claim 3; Page; 35pp; English.
XX
CC The present invention relates to a novel anti-CD28 antibody and its
CC therapeutic uses. The invention also provides a therapeutic composition
CC comprising the antibody. The antibody used in the invention is useful for
CC treating a pathological condition selected from transplant rejection,
CC chronic allograft vasculopathy, graft-versus-host disease, T-lymphocyte-
CC mediated autoimmune diseases, hypertension, allergic phenomena and
CC chronic inflammatory diseases. The present sequence is a specifically
CC claimed anti-CD28 antibody light chain region which comprises VL region
CC of a humanized CD28 antibody, and a human c kappa region (accession
CC number: BAC01725) used in the invention. Note: The present sequence is
CC not shown in the specification, but is a claimed fragment of an anti-CD28
CC antibody light chain given in the sequence listing (seeAZM49068).
XX
SQ Sequence 214 AA;
Query Match 99.9%; Score 1117; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 60
Qy 61 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
RESULT 2 from 2.rag database.
AZM49068
ID AZM49068 standard; protein; 234 AA.
XX
DT 13-OCT-2011 (first entry)
XX
DE Anti-CD28 antibody light chain region, SEQ ID 6.
XX
KW CD28; T cell surface glycoprotein CD28; allergy; antiallergic;
KW antibody therapy; antiinflammatory; autoimmune disease;
KW chronic inflammation; graft versus host disease; humanized antibody;
KW hypertension; hypotensive; immunosuppressive; light chain; mutein;
KW therapeutic; transplant rejection; vascular disease.
XX
OS Mus sp.
OS Homo sapiens.
OS Chimeric.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Peptide 1..20
FT /label= Murine_CD28.3_antibody_variable_light_chain_signa
FT l_peptide
FT Region 21..128
FT /label= Anti-CD28_variable_light_chain
FT Misc-difference 29
FT /note= "Mutation occurred site"
FT Misc-difference 33
FT /note= "Mutation occurred site"
FT Misc-difference 37
FT /note= "Mutation occurred site"
FT Misc-difference 38
FT /note= "Mutation occurred site"
FT Misc-difference 44
FT /note= "Mutation occurred site"
FT Region 52..59
FT /label= Complementarity_determining_region_1
FT Misc-difference 60
FT /note= "Mutation occurred site"
FT Region 70..77
FT /label= Complementarity_determining_region_2
FT Misc-difference 94
FT /note= "Mutation occurred site"
FT Misc-difference 96
FT /note= "Mutation occurred site"
FT Misc-difference 100
FT /note= "Mutation occurred site"
FT Region 110..116
FT /label= Complementarity_determining_region_3
FT Misc-difference 116
FT /label= Cys, Ala, Asn
FT Region 129..234
FT /label= Human_c_kappa_region
XX
CC PN WO2011101791-A1.
XX
CC PD 25-AUG-2011.
XX
CC PF 16-FEB-2011; 2011WO-IB050646.
CC PI Mary C, Poirier N, Vanhove B;
XX
DR WPI; 2011-K92195/58.
DR N-PSDB; AZM49067.
XX
CC PT New anti-CD28 antibody, useful for preparing therapeutic composition for
CC PT treating a pathological condition selected from transplant rejection,
CC PT chronic allograft vasculopathy, graft-versus-host disease, and
CC PT hypertension.
XX
CC PS Example 1; SEQ ID NO 6; 35pp; English.
XX
CC The present invention relates to a novel anti-CD28 antibody and its
CC therapeutic uses. The invention also provides a therapeutic composition
CC comprising the antibody. The antibody used in the invention is useful for
CC treating a pathological condition selected from transplant rejection,
CC chronic allograft vasculopathy, graft-versus-host disease, T-lymphocyte-
CC mediated autoimmune diseases, hypertension, allergic phenomena and
CC chronic inflammatory diseases. The present sequence is an an anti-CD28
CC antibody heavy chain region which comprises an anti-CD8 humanized
CC antibody VH region, a human CH1 region (accession number: AAF03881)
CC (accession number: BAC01725) and a native murine CD28.3 antibody light
CC chain leader peptide used in an exemplification of the invention.
XX
SQ Sequence 234 AA;
Query Match 99.9%; Score 1117; Length 234;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 80
Qy 61 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 140
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 200
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 201 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 234
12. Claim(s) 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mary et al., US 8,785,604 B2 (published July 22, 2014/ IDS reference, U.S.Patents Document #1 submitted September 8, 2023). Mary discloses an anti-CD28 antibody in monovalent form such as a Fab fragment, see page 1, lines 31-36; and paragraph bridging pages 3 and 4.
Mary discloses “…recombinant antibodies comprising a CD28-binding site associate with one or more heterologous polypeptide(s).”, see page 4, lines 6 and 7. The recombinant Fab fragment contains a heavy chain with a sequence of sequence 4 and a light chain with a sequence of sequence 6, see page 4, lines 12-14. Mary’s sequence 4 is the same as Applicant’s SEQ ID NO: 1 and sequence 6 is the same as Applicant’s SEQ ID NO: 2, see sequence alignments on the following pages.
The disclosed therapeutic composition comprises the said CD28 Fab antibody with a pharmaceutically acceptable excipient and “formulated at a dose of from 0.5 to 20 mg/Kg,”, see page 7, lines 1-6. The disclosed therapeutic composition comprises the said CD28 Fab’ antibody with a pharmaceutically acceptable excipient and “formulated at a dose of from 0.5 to 20 mg/Kg,”, see page 7, lines 1-6. The composition is suitable for parenteral administration, as well as sub-cutaneous or intra-venous injection, see page 7, lines 3-6. It is art known an injection is implemented via a medical device, a syringe to deliver a composition. Absent evidence to the contrary, the prior art reads on a syringe to deliver the injection of the disclosed composition.
RESULT 1 from 1.rai database.
US-13-577-103A-4
Sequence 4, US/13577103A
Patent No. 8785604
GENERAL INFORMATION
APPLICANT: TcL PHARMA
APPLICANT: INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
APPLICANT: (INSERM)
APPLICANT: MARY, Caroline
APPLICANT: POIRIER, Nicolas
APPLICANT: VANHOVE, Bernard
TITLE OF INVENTION: ANTI-CD28 HUMANIZED ANTIBODIES
FILE REFERENCE: MJP/ll - F2173/3 WO
CURRENT APPLICATION NUMBER: US/13/577,103A
CURRENT FILING DATE: 2012-09-27
PRIOR APPLICATION NUMBER: EP 10290080.0
PRIOR FILING DATE: 2010-02-18
NUMBER OF SEQ ID NOS: 31
SEQ ID NO 4
LENGTH: 251
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Signal-VH-hCH1
Query Match 100.0%; Score 1221; Length 251;
Best Local Similarity 100.0%;
Matches 231; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 80
Qy 62 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 140
Qy 122 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 200
Qy 182 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 232
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 201 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 251
RESULT 1 from 2.rai database.
US-13-577-103A-6
Sequence 6, US/13577103A
Patent No. 8785604
GENERAL INFORMATION
APPLICANT: TcL PHARMA
APPLICANT: INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
APPLICANT: (INSERM)
APPLICANT: MARY, Caroline
APPLICANT: POIRIER, Nicolas
APPLICANT: VANHOVE, Bernard
TITLE OF INVENTION: ANTI-CD28 HUMANIZED ANTIBODIES
FILE REFERENCE: MJP/ll - F2173/3 WO
CURRENT APPLICATION NUMBER: US/13/577,103A
CURRENT FILING DATE: 2012-09-27
PRIOR APPLICATION NUMBER: EP 10290080.0
PRIOR FILING DATE: 2010-02-18
NUMBER OF SEQ ID NOS: 31
SEQ ID NO 6
LENGTH: 234
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Signal-VL-hCkappa
FEATURE:
NAME/KEY: MISC_FEATURE
LOCATION: (116)..(116)
OTHER INFORMATION: Xaa = Cys or Ala
Query Match 99.9%; Score 1117; Length 234;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 80
Qy 61 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 140
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 200
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 201 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 234
Claim Rejections - 35 USC § 103
13. 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 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.
14. 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.
15. Claim(s) 15 is rejected under 35 U.S.C. 103 as being unpatentable over Mary et al., WO 2011/101791 A1 (published 25 August 2011/ IDS reference, Foreign Patent Document #1 submitted September 8, 2023), and further in view of Classon et al., WO 2012/047567 A1 (published 12 April 2012). Mary teaches “…recombinant antibodies comprising a CD28-binding site associate with one or more heterologous polypeptide(s).”, see page 4, lines 6 and 7. The recombinant Fab’ fragment contains a heavy chain that is sequence 4 and a light chain that is sequence 6, see page 4, lines 12-14. Mary’s sequence 4 is the same as Applicant’s SEQ ID NO: 1 and sequence 6 is the same as Applicant’s SEQ ID NO: 2, see sequence alignments on the following pages.
The taught therapeutic composition comprises the said CD28 Fab’ antibody with a pharmaceutically acceptable excipient and “formulated at a dose of from 0.5 to 20 mg/Kg,”, see page 7, lines 1-6. The composition is suitable for parenteral administration, as well as sub-cutaneous or intra-venous injection, see page 7, lines 3-6. It is art known an injection is implemented via a medical device to deliver a composition.
Mary does not teach explicitly teach the syringe comprising the taught pharmaceutical composition.
However, Classon teaches the administration of binding molecules including antigen-binding fragments that bind to CD48 and manners of administration, see abstract; page 8, section 0037; and Therapeutic Formulation…segment spanning pages 20-22.
It would have been obvious to one of ordinary skill in the art at before the effective filing date of the claimed invention was made to administer the taught immunotherapeutic composition, an anti-CD28 Fab’ in a syringe to deliver the composition subcutaneously or intravenously, see page 21, section 0081. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings well known in the art, as presented in Classon syringe delivery devices, injectable preparations of the CD48 binding molecules are injected for the treatment and/or amelioration of maladies associated with or mediated by CD48 activity, see sections 0078-0086 spanning pages 20-22.
RESULT 1 from 1.rag database.
AZM49080
ID AZM49080 standard; protein; 231 AA.
XX
AC AZM49080;
XX
DT 13-OCT-2011 (first entry)
XX
DE Anti-CD28 antibody heavy chain region.
XX
KW CD28; T cell surface glycoprotein CD28; allergy; antiallergic;
KW antibody therapy; antiinflammatory; autoimmune disease;
KW chronic inflammation; graft versus host disease; heavy chain;
KW humanized antibody; hypertension; hypotensive; immunosuppressive; mutein;
KW therapeutic; transplant rejection; vascular disease.
XX
OS Homo sapiens.
OS Mus sp.
OS Chimeric.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Region 1..120
FT /label= Anti-CD28_variable_heavy_chain
FT Misc-difference 11
FT /note= "Wild-type Val substituted by Lys"
FT Misc-difference 18
FT /note= "Wild-type Arg substituted by Lys"
FT Misc-difference 19
FT /note= "Wild-type Leu substituted by Val"
FT Region 29..32
FT /label= Complementarity_determining_region_1
FT Region 47..63
FT /label= Complementarity_determining_region_2
FT Misc-difference 62
FT /note= "Wild-type Lys substituted by Gln"
FT Misc-difference 87
FT /note= "Wild-type Ser substituted by Pro"
FT Region 96..108
FT /label= Complementarity_determining_region_3
FT Region 121..211
FT /label= Human_CH1
XX
CC PN WO2011101791-A1.
XX
CC PD 25-AUG-2011.
XX
CC PF 16-FEB-2011; 2011WO-IB050646.
XX
PR 18-FEB-2010; 2010EP-00290080.
PR 13-JUL-2010; 2010EP-00290389.
XX
CC PA (TCLP-) TCL PHARMA.
CC PA (INRM ) INSERM INST NAT SANTE&RECH MEDICALE.
XX
CC PI Mary C, Poirier N, Vanhove B;
XX
DR WPI; 2011-K92195/58.
DR N-PSDB; AZM49065.
XX
CC PT New anti-CD28 antibody, useful for preparing therapeutic composition for
CC PT treating a pathological condition selected from transplant rejection,
CC PT chronic allograft vasculopathy, graft-versus-host disease, and
CC PT hypertension.
XX
CC PS Claim 3; Page; 35pp; English.
XX
CC The present invention relates to a novel anti-CD28 antibody and its
CC therapeutic uses. The invention also provides a therapeutic composition
CC comprising the antibody. The antibody used in the invention is useful for
CC treating a pathological condition selected from transplant rejection,
CC chronic allograft vasculopathy, graft-versus-host disease, T-lymphocyte-
CC mediated autoimmune diseases, hypertension, allergic phenomena and
CC chronic inflammatory diseases. The present sequence is a specifically
CC claimed anti-CD28 antibody heavy chain region which comprises an anti-CD8
CC humanized antibody VH region, and a human CH1 region (accession number:
CC AAF03881) used in the invention. Note: The present sequence is not shown
CC in the specification, but is a claimed fragment of an anti-CD28 antibody
CC heavy chain given in the sequence listing (seeAZM49066).
XX
SQ Sequence 231 AA;
Query Match 100.0%; Score 1221; Length 231;
Best Local Similarity 100.0%;
Matches 231; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 60
Qy 62 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 120
Qy 122 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 182 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 232
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 231
RESULT 4 from 1.rng database.
AZM49066
ID AZM49066 standard; protein; 251 AA.
XX
AC AZM49066;
XX
DT 13-OCT-2011 (first entry)
XX
DE Anti-CD28 antibody heavy chain region, SEQ ID 4.
XX
KW CD28; T cell surface glycoprotein CD28; allergy; antiallergic;
KW antibody therapy; antiinflammatory; autoimmune disease;
KW chronic inflammation; graft versus host disease; heavy chain;
KW humanized antibody; hypertension; hypotensive; immunosuppressive; mutein;
KW therapeutic; transplant rejection; vascular disease.
XX
OS Homo sapiens.
OS Mus sp.
OS Chimeric.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Peptide 1..20
FT /label= Murine_CD28.3_antibody_variable_heavy_chain_signa
FT l_peptide
FT Region 21..140
FT /label= Anti-CD28_variable_heavy_chain
FT Misc-difference 31
FT /note= "Wild-type Val substituted by Lys"
FT Misc-difference 38
FT /note= "Wild-type Arg substituted by Lys"
FT Misc-difference 39
FT /note= "Wild-type Leu substituted by Val"
FT Region 49..52
FT /label= Complementarity_determining_region_1
FT Region 67..83
FT /label= Complementarity_determining_region_2
FT Misc-difference 82
FT /note= "Wild-type Lys substituted by Gln"
FT Misc-difference 107
FT /note= "Wild-type Ser substituted by Pro"
FT Region 116..128
FT /label= Complementarity_determining_region_3
FT Region 141..251
FT /label= Human_CH1
XX
CC PN WO2011101791-A1.
XX
CC PD 25-AUG-2011.
XX
CC PF 16-FEB-2011; 2011WO-IB050646.
XX
PR 18-FEB-2010; 2010EP-00290080.
PR 13-JUL-2010; 2010EP-00290389.
XX
CC PA (TCLP-) TCL PHARMA.
CC PA (INRM ) INSERM INST NAT SANTE&RECH MEDICALE.
XX
CC PI Mary C, Poirier N, Vanhove B;
XX
DR WPI; 2011-K92195/58.
DR N-PSDB; AZM49065.
XX
CC PT New anti-CD28 antibody, useful for preparing therapeutic composition for
CC PT treating a pathological condition selected from transplant rejection,
CC PT chronic allograft vasculopathy, graft-versus-host disease, and
CC PT hypertension.
XX
CC PS Example 1; SEQ ID NO 4; 35pp; English.
XX
CC The present invention relates to a novel anti-CD28 antibody and its
CC therapeutic uses. The invention also provides a therapeutic composition
CC comprising the antibody. The antibody used in the invention is useful for
CC treating a pathological condition selected from transplant rejection,
CC chronic allograft vasculopathy, graft-versus-host disease, T-lymphocyte-
CC mediated autoimmune diseases, hypertension, allergic phenomena and
CC chronic inflammatory diseases. The present sequence is an anti-CD28
CC antibody heavy chain region which comprises an anti-CD8 humanized
CC antibody VH region, a human CH1 region (accession number: AAF03881) and a
CC native murine CD28.3 antibody heavy chain leader peptide used in an
CC exemplification of the invention. Note: The present sequence is described
CC as SEQ ID NO:4 in the sequence listing , but it differs from the sequence
CC given as SEQ ID NO:4 in claim 5 (seeAZM49070).
XX
SQ Sequence 251 AA;
Query Match 100.0%; Score 1221; Length 251;
Best Local Similarity 100.0%;
Matches 231; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 80
Qy 62 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 140
Qy 122 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 200
Qy 182 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 232
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 201 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 251
RESULT 1 from 2.rng database.
AZM49081
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID AZM49081 standard; protein; 214 AA.
XX
AC AZM49081;
XX
DT 13-OCT-2011 (first entry)
XX
DE Anti-CD28 antibody light chain region.
XX
KW CD28; T cell surface glycoprotein CD28; allergy; antiallergic;
KW antibody therapy; antiinflammatory; autoimmune disease;
KW chronic inflammation; graft versus host disease; humanized antibody;
KW hypertension; hypotensive; immunosuppressive; light chain; mutein;
KW therapeutic; transplant rejection; vascular disease.
XX
OS Mus sp.
OS Homo sapiens.
OS Chimeric.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Region 1..108
FT /label= Anti-CD28_variable_light_chain
FT Misc-difference 9
FT /note= "Mutation occurred site"
FT Misc-difference 13
FT /note= "Mutation occurred site"
FT Misc-difference 17
FT /note= "Mutation occurred site"
FT Misc-difference 18
FT /note= "Mutation occurred site"
FT Misc-difference 24
FT /note= "Mutation occurred site"
FT Region 32..39
FT /label= Complementarity_determining_region_1
FT Misc-difference 40
FT /note= "Mutation occurred site"
FT Region 50..57
FT /label= Complementarity_determining_region_2
FT Misc-difference 74
FT /note= "Mutation occurred site"
FT Misc-difference 76
FT /note= "Mutation occurred site"
FT Misc-difference 80
FT /note= "Mutation occurred site"
FT Region 90..96
FT /label= Complementarity_determining_region_3
FT Misc-difference 96
FT /label= Cys, Ala, Asn
FT Region 109..194
FT /label= Human_c_kappa_region
XX
CC PN WO2011101791-A1.
XX
CC PD 25-AUG-2011.
XX
CC PF 16-FEB-2011; 2011WO-IB050646.
XX
PR 18-FEB-2010; 2010EP-00290080.
PR 13-JUL-2010; 2010EP-00290389.
XX
CC PA (TCLP-) TCL PHARMA.
CC PA (INRM ) INSERM INST NAT SANTE&RECH MEDICALE.
XX
CC PI Mary C, Poirier N, Vanhove B;
XX
DR WPI; 2011-K92195/58.
DR N-PSDB; AZM49067.
XX
CC PT New anti-CD28 antibody, useful for preparing therapeutic composition for
CC PT treating a pathological condition selected from transplant rejection,
CC PT chronic allograft vasculopathy, graft-versus-host disease, and
CC PT hypertension.
XX
CC PS Claim 3; Page; 35pp; English.
XX
CC The present invention relates to a novel anti-CD28 antibody and its
CC therapeutic uses. The invention also provides a therapeutic composition
CC comprising the antibody. The antibody used in the invention is useful for
CC treating a pathological condition selected from transplant rejection,
CC chronic allograft vasculopathy, graft-versus-host disease, T-lymphocyte-
CC mediated autoimmune diseases, hypertension, allergic phenomena and
CC chronic inflammatory diseases. The present sequence is a specifically
CC claimed anti-CD28 antibody light chain region which comprises VL region
CC of a humanized CD28 antibody, and a human c kappa region (accession
CC number: BAC01725) used in the invention. Note: The present sequence is
CC not shown in the specification, but is a claimed fragment of an anti-CD28
CC antibody light chain given in the sequence listing (seeAZM49068).
XX
SQ Sequence 214 AA;
Query Match 99.9%; Score 1117; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 60
Qy 61 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
RESULT 2 from 2.rag database.
AZM49068
ID AZM49068 standard; protein; 234 AA.
XX
AC AZM49068;
XX
DT 13-OCT-2011 (first entry)
XX
DE Anti-CD28 antibody light chain region, SEQ ID 6.
XX
KW CD28; T cell surface glycoprotein CD28; allergy; antiallergic;
KW antibody therapy; antiinflammatory; autoimmune disease;
KW chronic inflammation; graft versus host disease; humanized antibody;
KW hypertension; hypotensive; immunosuppressive; light chain; mutein;
KW therapeutic; transplant rejection; vascular disease.
XX
OS Mus sp.
OS Homo sapiens.
OS Chimeric.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Peptide 1..20
FT /label= Murine_CD28.3_antibody_variable_light_chain_signa
FT l_peptide
FT Region 21..128
FT /label= Anti-CD28_variable_light_chain
FT Misc-difference 29
FT /note= "Mutation occurred site"
FT Misc-difference 33
FT /note= "Mutation occurred site"
FT Misc-difference 37
FT /note= "Mutation occurred site"
FT Misc-difference 38
FT /note= "Mutation occurred site"
FT Misc-difference 44
FT /note= "Mutation occurred site"
FT Region 52..59
FT /label= Complementarity_determining_region_1
FT Misc-difference 60
FT /note= "Mutation occurred site"
FT Region 70..77
FT /label= Complementarity_determining_region_2
FT Misc-difference 94
FT /note= "Mutation occurred site"
FT Misc-difference 96
FT /note= "Mutation occurred site"
FT Misc-difference 100
FT /note= "Mutation occurred site"
FT Region 110..116
FT /label= Complementarity_determining_region_3
FT Misc-difference 116
FT /label= Cys, Ala, Asn
FT Region 129..234
FT /label= Human_c_kappa_region
XX
CC PN WO2011101791-A1.
XX
CC PD 25-AUG-2011.
XX
CC PF 16-FEB-2011; 2011WO-IB050646.
XX
PR 18-FEB-2010; 2010EP-00290080.
PR 13-JUL-2010; 2010EP-00290389.
XX
CC PA (TCLP-) TCL PHARMA.
CC PA (INRM ) INSERM INST NAT SANTE&RECH MEDICALE.
XX
CC PI Mary C, Poirier N, Vanhove B;
XX
DR WPI; 2011-K92195/58.
DR N-PSDB; AZM49067.
XX
CC PT New anti-CD28 antibody, useful for preparing therapeutic composition for
CC PT treating a pathological condition selected from transplant rejection,
CC PT chronic allograft vasculopathy, graft-versus-host disease, and
CC PT hypertension.
XX
CC PS Example 1; SEQ ID NO 6; 35pp; English.
XX
CC The present invention relates to a novel anti-CD28 antibody and its
CC therapeutic uses. The invention also provides a therapeutic composition
CC comprising the antibody. The antibody used in the invention is useful for
CC treating a pathological condition selected from transplant rejection,
CC chronic allograft vasculopathy, graft-versus-host disease, T-lymphocyte-
CC mediated autoimmune diseases, hypertension, allergic phenomena and
CC chronic inflammatory diseases. The present sequence is an an anti-CD28
CC antibody heavy chain region which comprises an anti-CD8 humanized
CC antibody VH region, a human CH1 region (accession number: AAF03881)
CC (accession number: BAC01725) and a native murine CD28.3 antibody light
CC chain leader peptide used in an exemplification of the invention.
XX
SQ Sequence 234 AA;
Query Match 99.9%; Score 1117; Length 234;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 80
Qy 61 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 140
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 200
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 201 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 234
16. Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mary et al., US 8,785,604 B2 (published July 22, 2014/ IDS reference, U.S.Patents Document #1 submitted September 8, 2023), and further in view of Classon et al., WO 2012/047567 A1 (published 12 April 2012). Mary teaches an anti-CD28 antibody in monovalent form such as a Fab fragment, see page 1, lines 31-36; and paragraph bridging pages 3 and 4.
Mary teaches “…recombinant antibodies comprising a CD28-binding site associate with one or more heterologous polypeptide(s).”, see page 4, lines 6 and 7. The recombinant Fab fragment contains a heavy chain with a sequence of sequence 4 and a light chain with a sequence of sequence 6, see page 4, lines 12-14. Mary’s sequence 4 is the same as Applicant’s SEQ ID NO: 1 and sequence 6 is the same as Applicant’s SEQ ID NO: 2, see sequence alignments on the following pages.
The Fab antibody fragments “…can be conjugated with water soluble polymers such as polyethylene glycol (PEGylation).”, see page 5, lines 14-18; and Example 7 beginning on page 15.
The disclosed therapeutic composition comprises the said CD28 Fab antibody with a pharmaceutically acceptable excipient and “formulated at a dose of from 0.5 to 20 mg/Kg,”, see page 7, lines 1-6.
Mary does not teach explicitly teach the syringe comprising the taught pharmaceutical composition.
However, Classon teaches the administration of binding molecules including antigen-binding fragments that bind to CD48 and manners of administration, see abstract; page 8, section 0037; and Therapeutic Formulation…segment spanning pages 20-22.
It would have been obvious to one of ordinary skill in the art at before the effective filing date of the claimed invention was made to administer the taught immunotherapeutic composition, an anti-CD28 Fab’ in a syringe to deliver the composition subcutaneously or intravenously, see page 21, section 0081. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings well known in the art, as presented in Classon syringe delivery devices, injectable preparations of the CD48 binding molecules are injected for the treatment and/or amelioration of maladies associated with or mediated by CD48 activity, see sections 0078-0086 spanning pages 20-22.
RESULT 1 from 1.rai database.
US-13-577-103A-4
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
Sequence 4, US/13577103A
Patent No. 8785604
GENERAL INFORMATION
APPLICANT: TcL PHARMA
APPLICANT: INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
APPLICANT: (INSERM)
APPLICANT: MARY, Caroline
APPLICANT: POIRIER, Nicolas
APPLICANT: VANHOVE, Bernard
TITLE OF INVENTION: ANTI-CD28 HUMANIZED ANTIBODIES
FILE REFERENCE: MJP/ll - F2173/3 WO
CURRENT APPLICATION NUMBER: US/13/577,103A
CURRENT FILING DATE: 2012-09-27
PRIOR APPLICATION NUMBER: EP 10290080.0
PRIOR FILING DATE: 2010-02-18
NUMBER OF SEQ ID NOS: 31
SEQ ID NO 4
LENGTH: 251
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Signal-VH-hCH1
Query Match 100.0%; Score 1221; Length 251;
Best Local Similarity 100.0%;
Matches 231; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 VQLQQSGAELKKPGASVKVSCKASGYTFTEYIIHWIKLRSGQGLEWIGWFYPGSNDIQYN 80
Qy 62 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 121
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 AQFKGKATLTADKSSSTVYMELTGLTPEDSAVYFCARRDDFSGYDALPYWGQGTLVTVSA 140
Qy 122 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 200
Qy 182 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 232
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 201 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCAA 251
RESULT 1 from 2.rai database.
US-13-577-103A-6
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
Sequence 6, US/13577103A
Patent No. 8785604
GENERAL INFORMATION
APPLICANT: TcL PHARMA
APPLICANT: INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
APPLICANT: (INSERM)
APPLICANT: MARY, Caroline
APPLICANT: POIRIER, Nicolas
APPLICANT: VANHOVE, Bernard
TITLE OF INVENTION: ANTI-CD28 HUMANIZED ANTIBODIES
FILE REFERENCE: MJP/ll - F2173/3 WO
CURRENT APPLICATION NUMBER: US/13/577,103A
CURRENT FILING DATE: 2012-09-27
PRIOR APPLICATION NUMBER: EP 10290080.0
PRIOR FILING DATE: 2010-02-18
NUMBER OF SEQ ID NOS: 31
SEQ ID NO 6
LENGTH: 234
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Signal-VL-hCkappa
FEATURE:
NAME/KEY: MISC_FEATURE
LOCATION: (116)..(116)
OTHER INFORMATION: Xaa = Cys or Ala
Query Match 99.9%; Score 1117; Length 234;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 DIQMTQSPSSLSASVGDRVTITCKTNENIYSNLAWYQQKDGKSPQLLIYAATHLVEGVPS 80
Qy 61 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 RFSGSGSGTQYSLTISSLQPEDFGNYYCQHFWGTPXTFGGGTKLEIKRTVAAPSVFIFPP 140
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 200
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 201 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 234
Conclusion
17. 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.
18. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached on 8AM-8PM, Monday through Friday.
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, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
August 3, 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643
Prosecution Insights