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 .
Claim Status
2. Applicant’s correspondence filed August 11, 2026, is acknowledged. In response to the Restriction Requirement of June 17, 2026, Applicant has elected the invention of Group III, claims 11-19, with traverse.
The basis for Applicant’s traversal is: “there is no undue burden” to examine all the pending claims, citing MPEP section 803.
Applicant’s argument is not found persuasive because: the Office has articulated clear reasoning for the Restriction Requirement, namely that the technical feature linking the inventions Groups I-IV does not constitute a special technical feature as defined by PCT rule 13.2 in view of the cited reference, and therefore restriction is proper.
Therefore, the Restriction Requirement is deemed proper and made FINAL.
Accordingly, claims 1-10 and 20 are withdrawn from further consideration for being drawn to the non-elected invention. Therefore, claims 1-20 are pending; claims 1-10 and 20 are withdrawn; and claims 11-19 are presently subject to examination.
Information Disclosure Statement
3. The listing of references in the specification (e.g., at para. [0149]) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The references should be placed on an information disclosure statement if Applicant would like them considered.
Objection to the Specification
4. The instant specification is objected to for the following reasons:
There are trademarks in this application that do not meet the requirements.
The use of the term (e.g., “Bayer” at para. [0122]), which is a trade name or a mark used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology whenever possible; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Please review the specification for other improper trademarks and correct as required.
Double Patenting
5. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the "right to exclude" granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/proces/file/efs/guidance/eTD-info-I.jsp.
A. Claims 11, 13, and 16 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-8 and 10-13 of U.S. Patent No. 11,518,813, filed April 10, 2020. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons:
The instant claims are directed to a trispecific antagonist, comprising: (1) an immunoglobulin scaffold comprising a CH3 domain; (2) a first targeting domain comprising one or more VEGF or VEGFR binding domains; (3) a second targeting domain comprising one or more Tie2 receptor or Ang binding domains; and (4) a third targeting domain comprising one or more PD-1 binding domains. Claim 13 recites: wherein the second targeting domain comprises SEQ ID NO:2. Claim 16 recites: wherein the third targeting domain comprises SEQ ID NO:90 and SEQ ID NO:91.
The reference claims are directed to a trispecific antagonist comprising: (1) an immunoglobulin scaffold comprising a CH3 domain; (2) a first targeting domain comprising and anti-PD-1 variable domain; (3) a second targeting domain that binds specifically to VEGF; and a (4) a third targeting domain comprising a peptide inhibitor of the angiopoietin/Tie-2 signaling pathways. Claim 3 recites that the antagonist comprises SEQ ID NOs: 137 or 138, which is identical to instant SEQ ID NOs: 90 and 91; claim 8 recites that the antagonist comprises SEQ ID NO: 209, which is identical to instant SEQ ID NO: 2. Alignments of the indicated sequences are presented at the end of this section for Applicant’s convenience.
The reference patent claims anticipate the instant claims, but the reference patent claims differ in scope from the instant claims because the reference patent claims require additional features not required in the instant claims. Therefore, the reference patent claims recite species encompassed by the instant claimed genus of trispecific antagonists, thereby anticipating the invention of the instant claims, but the reference claimed genus is not identical to the instant claimed genus. Therefore, the conflicting claims are not patentably distinct from each other.
B. Claim 11 is rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,647,773, filed June 28, 2019. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons:
The instant claims are directed to a trispecific antagonist, comprising: (1) an immunoglobulin scaffold comprising a CH3 domain; (2) a first targeting domain comprising one or more VEGF or VEGFR binding domains; (3) a second targeting domain comprising one or more Tie2 receptor or Ang binding domains; and (4) a third targeting domain comprising one or more PD-1 binding domains.
The reference claims are directed to a trispecific antagonist comprising: (1) an immunoglobulin scaffold comprising a CH3 domain; (2) a first targeting domain comprising and anti-PD-1 variable domain; (3) a second targeting domain that binds specifically to VEGF; and a (4) a third targeting domain comprising a peptide inhibitor of the angiopoietin/Tie-2 signaling pathways.
The reference patent claims anticipate the instant claims, but the reference patent claims differ in scope from the instant claims because the reference patent claims require additional features not required in the instant claims. Therefore, the reference patent claims recite species encompassed by the instant claimed genus of trispecific antagonists, thereby anticipating the invention of the instant claims, but the reference claimed genus is not identical to the instant claimed genus. Therefore, the conflicting claims are not patentably distinct from each other.
ALIGNMENT TO INSTANT SEQ ID NO: 2:
Query Match 100.0%; Score 310; Length 285;
Best Local Similarity 100.0%;
Matches 52; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSATHQEECEWDPWTCEHM 52
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 AQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSATHQEECEWDPWTCEHM 192
US-16-845-924-209
Filing date in PALM: 2020-04-10
Sequence 209, US/16845924
Publication No. US20200277388A1
GENERAL INFORMATION
APPLICANT: GENSUN BIOPHARMA INC.
TITLE OF INVENTION: TRISPECIFIC ANTAGONISTS
FILE REFERENCE: 2022-003 US1-CONT
CURRENT APPLICATION NUMBER: US/16/845,924
CURRENT FILING DATE: 2020-04-10
PRIOR APPLICATION NUMBER: 16/457,343
PRIOR FILING DATE: 2019-06-28
PRIOR APPLICATION NUMBER: US 62/691,658
PRIOR FILING DATE: 2018-06-29
PRIOR APPLICATION NUMBER: US 62/823,989
PRIOR FILING DATE: 2019-03-26
NUMBER OF SEQ ID NOS: 420
SEQ ID NO 209
LENGTH: 285
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
ALIGNMENT TO INSTANT SEQ ID NO: 90:
Query Match 100.0%; Score 627; Length 117;
Best Local Similarity 100.0%;
Matches 117; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGWIFPGSGNSKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGWIFPGSGNSKY 60
Qy 61 NENFKGRVTLTADTSTSTVYMELSSLRSEDTAVYYCASETYDYGDYWGQGTLVTVSS 117
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NENFKGRVTLTADTSTSTVYMELSSLRSEDTAVYYCASETYDYGDYWGQGTLVTVSS 117
US-16-845-924-137
Filing date in PALM: 2020-04-10
Sequence 137, US/16845924
Publication No. US20200277388A1
GENERAL INFORMATION
APPLICANT: GENSUN BIOPHARMA INC.
TITLE OF INVENTION: TRISPECIFIC ANTAGONISTS
FILE REFERENCE: 2022-003 US1-CONT
CURRENT APPLICATION NUMBER: US/16/845,924
CURRENT FILING DATE: 2020-04-10
PRIOR APPLICATION NUMBER: 16/457,343
PRIOR FILING DATE: 2019-06-28
PRIOR APPLICATION NUMBER: US 62/691,658
PRIOR FILING DATE: 2018-06-29
PRIOR APPLICATION NUMBER: US 62/823,989
PRIOR FILING DATE: 2019-03-26
NUMBER OF SEQ ID NOS: 420
SEQ ID NO 137
LENGTH: 117
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
ALIGNMENT TO INSTANT SEQ ID NO: 91:
Query Match 100.0%; Score 563; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSFLSASVGDRVTITCKASQNVGTNVAWYQQKPGKAPKALIYSASYRYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSFLSASVGDRVTITCKASQNVGTNVAWYQQKPGKAPKALIYSASYRYSGVPS 60
Qy 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQYYSYPYTFGQGTKLEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQYYSYPYTFGQGTKLEIK 107
US-16-845-924-138
Filing date in PALM: 2020-04-10
Sequence 138, US/16845924
Publication No. US20200277388A1
GENERAL INFORMATION
APPLICANT: GENSUN BIOPHARMA INC.
TITLE OF INVENTION: TRISPECIFIC ANTAGONISTS
FILE REFERENCE: 2022-003 US1-CONT
CURRENT APPLICATION NUMBER: US/16/845,924
CURRENT FILING DATE: 2020-04-10
PRIOR APPLICATION NUMBER: 16/457,343
PRIOR FILING DATE: 2019-06-28
PRIOR APPLICATION NUMBER: US 62/691,658
PRIOR FILING DATE: 2018-06-29
PRIOR APPLICATION NUMBER: US 62/823,989
PRIOR FILING DATE: 2019-03-26
NUMBER OF SEQ ID NOS: 420
SEQ ID NO 138
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
Claim Rejections - 35 USC § 112
6. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 19 is rejected under 35 U.S.C 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor regards as the invention.
Claim 19 recites the limitation "the bispecific antagonist of any one of claim 11.” There is insufficient antecedent basis for this limitation in the claim, because claim 11 is directed to a trispecific antagonist, not a bispecific antagonist. Appropriate clarification and/or correction is required.
Claim Rejections - 35 USC § 102
7. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
8. Claims 11-14, 16, and 19 are rejected under 35 U.S.C 102(a)(2) as anticipated by Sheng et al. (US 20200277388 A1, published September 3, 2020), in light of Oliner et al. (US 7138370 B2, published November 21, 2006; or US 20030229023 A1, published December 11, 2003).
Claim 11 is drawn to a trispecific antagonist, comprising: (1) an immunoglobulin scaffold comprising a CH3 domain; (2) a first targeting domain comprising one or more VEGF or VEGFR binding domains; (3) a second targeting domain comprising one or more Tie2 receptor or Ang binding domains; and (4) a third targeting domain comprising one or more PD-1 binding domains.
Claims 12 is drawn to the trispecific antagonist of claim 11, wherein the second targeting domain is inserted into a loop region of the CH3 domain.
Claim 13 is drawn to the trispecific antagonist of claim 11, wherein the second targeting domain comprises SEQ ID NO:2.
Claim 14 is drawn to the bispecific antagonist of claim 11, wherein the second targeting domain comprises a single copy or two copies of SEQ ID NO:6.
Claim 16 is drawn to the trispecific antagonist of claim 11, wherein the third targeting domain comprises SEQ ID NO:90 and SEQ ID NO:91.
Claim 19 is drawn to the pharmaceutical composition, comprising the bispecific antagonist of any one of claim 11; and a pharmaceutically acceptable carrier.
Sheng et al. (cited in the ISR) is directed to trispecific agonists (see the title). Sheng et al. disclose an immunoglobulin scaffold comprising CH3 domain; first targeting domain comprising VEGF or VEGFR binding domain (e.g., aflibercept domain); second targeting domain comprising one or more Tie2 receptor or Ang binding domains (e.g., Trebananib peptide); and a third targeting domain comprising one or more PD-1 binding domains (see e.g., Sheng et al. Figure 13, which demonstrates the features and is presented for Applicant’s convenience at the end of this section) (Claim 11).
Sheng et al. further discloses the second (angiopoietin/Tie-2) targeting domain can be inserted into a loop region of the CH3 domain at e.g., para. [0119] (Claim 12).
Sheng et al. further discloses wherein the second targeting comprises instant SEQ ID NO: 2 at e.g., para. [0176]. An alignment of Sheng et al. SEQ ID NO: 209 to instant SEQ ID NO: 2 is presented at the end of this section for Applicant’s convenience (Claim 12).
Sheng et al. further discloses wherein the third targeting domain comprises SEQ ID: NO 90 and 91 at e.g., para. [0140]. An alignment of Sheng et al. SEQ ID NOs: 137 and 138 to instant SEQ ID NOs: 90 and 91 is presented at the end of this section for Applicant’s convenience (Claim 16).
Sheng et al. contemplates pharmaceutical compositions having pharmaceutically acceptable carriers and comprising the agonist at e.g., para [0269] (Claim 19).
Sheng et al. do not explicitly disclose the features of instant claim 14: wherein the second targeting domain comprises a single copy or two copies of SEQ ID NO: 6. However, Sheng et al. discloses at para. [0177]: “Additional peptide inhibitors of Tie2 activation are described in U.S. Pat. No. 7,138,370 [Oliner et al.],” and that the peptide inhibitors described therein are exemplary. Sheng et al. also expressly incorporates any issued patent or patent application publication described therein at para [0055]. Oliner et al. disclose the A2 peptide sequence of instant SEQ ID NO: 6 at col. 8, ln. 15-45. An alignment of Oliner et al. SEQ ID NO: 124 to instant SEQ ID NO: 6 is presented at the end of this section for Applicant’s convenience (Claim 14).
Accordingly, Sheng et al. in light of Oliner et al., anticipates claims 11-14, 16, and 19.
ALIGNMENT TO INSTANT SEQ ID NO: 2:
Query Match 100.0%; Score 310; Length 285;
Best Local Similarity 100.0%;
Matches 52; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSATHQEECEWDPWTCEHM 52
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 AQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSATHQEECEWDPWTCEHM 192
US-16-845-924-209
Filing date in PALM: 2020-04-10
Sequence 209, US/16845924
Publication No. US20200277388A1
GENERAL INFORMATION
APPLICANT: GENSUN BIOPHARMA INC.
TITLE OF INVENTION: TRISPECIFIC ANTAGONISTS
FILE REFERENCE: 2022-003 US1-CONT
CURRENT APPLICATION NUMBER: US/16/845,924
CURRENT FILING DATE: 2020-04-10
PRIOR APPLICATION NUMBER: 16/457,343
PRIOR FILING DATE: 2019-06-28
PRIOR APPLICATION NUMBER: US 62/691,658
PRIOR FILING DATE: 2018-06-29
PRIOR APPLICATION NUMBER: US 62/823,989
PRIOR FILING DATE: 2019-03-26
NUMBER OF SEQ ID NOS: 420
SEQ ID NO 209
LENGTH: 285
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
ALIGNMENT TO INSTANT SEQ ID NO: 90:
Query Match 100.0%; Score 627; Length 117;
Best Local Similarity 100.0%;
Matches 117; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGWIFPGSGNSKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGWIFPGSGNSKY 60
Qy 61 NENFKGRVTLTADTSTSTVYMELSSLRSEDTAVYYCASETYDYGDYWGQGTLVTVSS 117
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NENFKGRVTLTADTSTSTVYMELSSLRSEDTAVYYCASETYDYGDYWGQGTLVTVSS 117
US-16-845-924-137
Filing date in PALM: 2020-04-10
Sequence 137, US/16845924
Publication No. US20200277388A1
GENERAL INFORMATION
APPLICANT: GENSUN BIOPHARMA INC.
TITLE OF INVENTION: TRISPECIFIC ANTAGONISTS
FILE REFERENCE: 2022-003 US1-CONT
CURRENT APPLICATION NUMBER: US/16/845,924
CURRENT FILING DATE: 2020-04-10
PRIOR APPLICATION NUMBER: 16/457,343
PRIOR FILING DATE: 2019-06-28
PRIOR APPLICATION NUMBER: US 62/691,658
PRIOR FILING DATE: 2018-06-29
PRIOR APPLICATION NUMBER: US 62/823,989
PRIOR FILING DATE: 2019-03-26
NUMBER OF SEQ ID NOS: 420
SEQ ID NO 137
LENGTH: 117
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
ALIGNMENT TO INSTANT SEQ ID NO: 91:
Query Match 100.0%; Score 563; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSFLSASVGDRVTITCKASQNVGTNVAWYQQKPGKAPKALIYSASYRYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSFLSASVGDRVTITCKASQNVGTNVAWYQQKPGKAPKALIYSASYRYSGVPS 60
Qy 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQYYSYPYTFGQGTKLEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQYYSYPYTFGQGTKLEIK 107
US-16-845-924-138
Filing date in PALM: 2020-04-10
Sequence 138, US/16845924
Publication No. US20200277388A1
GENERAL INFORMATION
APPLICANT: GENSUN BIOPHARMA INC.
TITLE OF INVENTION: TRISPECIFIC ANTAGONISTS
FILE REFERENCE: 2022-003 US1-CONT
CURRENT APPLICATION NUMBER: US/16/845,924
CURRENT FILING DATE: 2020-04-10
PRIOR APPLICATION NUMBER: 16/457,343
PRIOR FILING DATE: 2019-06-28
PRIOR APPLICATION NUMBER: US 62/691,658
PRIOR FILING DATE: 2018-06-29
PRIOR APPLICATION NUMBER: US 62/823,989
PRIOR FILING DATE: 2019-03-26
NUMBER OF SEQ ID NOS: 420
SEQ ID NO 138
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
ALIGNMENT TO INSTANT SEQ ID NO: 6:
US-10-269-695-124
Sequence 124, US/10269695
Publication No. US20030229023A1
GENERAL INFORMATION
APPLICANT: OLINER, JONATHAN DANIEL
APPLICANT: MIN, HOSUNG
TITLE OF INVENTION: SPECIFIC BINDING AGENTS OF HUMAN ANGIOPOIETIN-2
FILE REFERENCE: A-801A
CURRENT APPLICATION NUMBER: US/10/269,695
CURRENT FILING DATE: 2002-10-10
PRIOR APPLICATION NUMBER: US 60/414,155
PRIOR FILING DATE: 2002-09-27
PRIOR APPLICATION NUMBER: US 60/328,624
PRIOR FILING DATE: 2001-10-11
NUMBER OF SEQ ID NOS: 359
SEQ ID NO 124
LENGTH: 22
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Polypeptide capable of binding to Ang-2
Query Match 100.0%; Score 116; Length 22;
Best Local Similarity 100.0%;
Matches 22; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TNFMPMDDLEQRLYEQFILQQG 22
||||||||||||||||||||||
Db 1 TNFMPMDDLEQRLYEQFILQQG 22
PNG
media_image1.png
841
619
media_image1.png
Greyscale
Claim Rejections - 35 USC § 103
9. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
10. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
11. Claims 11-14, 16, and 19 are rejected under 35 U.S.C 103 as obvious over Sheng et al. (US 20200277388 A1, published September 3, 2020) in view of Oliner et al. (US 7138370 B2, published November 21, 2006; or US 20030229023 A1, published December 11, 2003).
Claim 11 is drawn to a trispecific antagonist, comprising: (1) an immunoglobulin scaffold comprising a CH3 domain; (2) a first targeting domain comprising one or more VEGF or VEGFR binding domains; (3) a second targeting domain comprising one or more Tie2 receptor or Ang binding domains; and (4) a third targeting domain comprising one or more PD-1 binding domains.
Claims 12 is drawn to the trispecific antagonist of claim 11, wherein the second targeting domain is inserted into a loop region of the CH3 domain.
Claim 13 is drawn to the trispecific antagonist of claim 11, wherein the second targeting domain comprises SEQ ID NO:2.
Claim 14 is drawn to the bispecific antagonist of claim 11, wherein the second targeting domain comprises a single copy or two copies of SEQ ID NO:6.
Claim 16 is drawn to the trispecific antagonist of claim 11, wherein the third targeting domain comprises SEQ ID NO:90 and SEQ ID NO:91.
Claim 19 is drawn to the pharmaceutical composition, comprising the bispecific antagonist of any one of claim 11; and a pharmaceutically acceptable carrier.
Sheng et al. (cited in the ISR) is directed to trispecific agonists (see the title) and relates generally to cancer treatment (see “Field” at para. [0002]). Sheng et al. discloses an immunoglobulin scaffold comprising CH3 domain; first targeting domain comprising VEGF or VEGFR binding domain (e.g., aflibercept domain); second targeting domain comprising one or more Tie2 receptor or Ang binding domains (e.g., Trebananib peptide); and a third targeting domain comprising one or more PD-1 binding domains. See e.g., Figure 13 of Sheng et al., demonstrating the features and the N to C orientation of the respective construct. Sheng et al. further discloses at para. [0207]: “FIGS. 5A-5E show a variety of different trispecific antagonists where (1) the VH1 and VL1 regions correspond to anti-PD-1 variable domains or another checkpoint antibody; (2) VH and VL of bevacizumab or another anti-VEGF-A antibody (3) the circles correspond to trebananib peptide. As shown in these figures, these components can be rearranged in multiple configurations.” Sheng et al. therefore broadly teach replacing the aflibercept domain with bevacizumab or another anti-VEGF-A antibody. Sheng et al. further disclose the second (angiopoietin/Tie-2) targeting domain can be inserted into a loop region of the CH3 domain at e.g., para. [0119]. Sheng et al. further disclose wherein the second targeting comprises instant SEQ ID NO: 2 at e.g., para. [0176]. An alignment of Sheng et al. SEQ ID NO: 209 to instant SEQ ID NO: 2 is presented at the end of this section for Applicant’s convenience. Sheng et al. further disclose wherein the third targeting domain comprises SEQ ID: NO 90 and 91 at e.g., para. [0140]. An alignment of Sheng et al. SEQ ID NOs: 137 and 138 to instant SEQ ID NOs: 90 and 91 is presented at the end of this section for Applicant’s convenience. Sheng et al. contemplate pharmaceutical compositions having pharmaceutically acceptable carriers and comprising the agonist at e.g., para [0269]; and the advantages of administering lower doses for lower toxicity at para. [0311]. SEQ ID NO: 287 of Sheng et al. disclose a (G4S)x4 linker.
Sheng et al. do not explicitly disclose the features of instant claim 14: wherein the second targeting domain comprises a single copy or two copies of SEQ ID NO: 6. However, Sheng et al. disclose at para. [0177]: “Additional peptide inhibitors of Tie2 activation are described in U.S. Pat. No. 7,138,370 [Oliner et al.],” and that the peptide inhibitors described therein are exemplary. Sheng et al. also expressly incorporates by reference any issued patent or patent application publication described therein at para [0055].
Oliner et al. disclose the A2 peptide sequence of instant SEQ ID NO: 6 at col. 8, ln. 15-45. An alignment of Oliner et al. SEQ ID NO: 124 to instant SEQ ID NO: 6 is presented at the end of this section for Applicant’s convenience (Claims 11-14, 16, and 19). Oliner et al. also teach that “Any of these peptides may be linked in tandem (i.e., sequentially), with or without linkers” at col. 31, ln. 29-30, and “Any ‘linker’ group is optional. When present, its chemical structure is not critical, since it serves primarily as a spacer. The linker is preferably made up of amino acids linked together by peptide bonds. Thus, in preferred embodiments, the linker is made up of from 1 to 20 amino acids linked by peptide bonds, wherein the amino acids are selected from the 20 naturally occurring amino acids” at col. 33, ln. 57-63. Accordingly, Oliner et al.’s broad teaching that the peptides, i.e., instant SEQ ID NO: 6, can be linked in tandem; that the linker chemical structure is not critical; and Sheng et al.’s teaching of the (G4S)x4 linker, reads on instant SEQ ID NO: 7.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to modify the peptide of Oliner et al. (i.e., instant SEQ ID NO: 6) to arrive at instant SEQ ID NO: 7 because Oliner et al. teach linking its peptides in tandem with a linker. Oliner et al. teach the chemical structure of said linker is not critical, and suggests using one that is up to 20 amino acids long. Sheng et al. provide such a linker, a (G4S)x4 linker that is 20 amino acids long. Combining two copies of the peptide disclosed by Oliner et al. with the linker of Sheng et al. renders instant SEQ ID NO: 7. One of ordinary skill in the art would be motivated to use any of the linkers of Sheng et al. with a reasonable expectation of success because Oliner et al. disclose and suggest that any linker 20 amino acids or less in length is likely to work, because “chemical structure is not critical.” However, Sheng et al. describes the use of the same linker as claimed. Therefore, one of ordinary skill in the art would conclude with a reasonable expectation of success that the teachings of Sheng et al. and Oliner et al. would render the claimed invention obvious.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine the prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Accordingly, Sheng et al. in view of Oliner et al. renders claims 11-14, 16, and 19 obvious.
12. Claims 15 and 17-18 are rejected under 35 U.S.C 103 as obvious over Sheng et al. in view of Oliner et al. as applied to claims 11-14, 16 and 19, and further in view of Baehner et al. (WO 2010040508 A1, published April 15, 2010).
Claim 15 is drawn to the trispecific antagonist of claim 11, wherein the first targeting domain comprises SEQ ID NO:88 and SEQ ID NO:89.
Claim 17 is drawn to the trispecific antagonist of claim 11, wherein the first targeting domain comprises SEQ ID NO:88 and SEQ ID NO:89 and is attached to a C-terminal of the immunoglobulin scaffold, wherein the second targeting domain comprises SEQ ID NO:2 and is inserted into a loop region of the CH3 domain of the immunoglobulin scaffold, and wherein the third targeting domain comprises SEQ ID NO:90 and SEQ ID NO:91 and is attached to a N- terminal of the immunoglobulin scaffold.
Claim 18 is drawn to the trispecific antagonist of claim 11, wherein the first targeting domain comprises SEQ ID NO:88 and SEQ ID NO:89 and is attached to a C-terminal of the immunoglobulin scaffold, wherein the second targeting domain comprises SEQ ID NO:7 and is inserted into a loop region of the CH3 domain of the immunoglobulin scaffold, and wherein the third targeting domain comprises SEQ ID NO:90 and SEQ ID NO:91 and is attached to a N- terminal of the immunoglobulin scaffold.
The teachings of Sheng et al. and Oliner et al. are discussed above.
Sheng et al. and Oliner et al. do not explicitly disclose the subject matter of claims 15 and 17-18, namely, wherein the first targeting domain comprises SEQ ID NO:88 and SEQ ID NO:89.
Baehner et al. is directed to VEGF / ANG-2 bispecific antibodies for treating cancer (see the title and pg. 1, ln. 1-17). Baehner et al. explain at pg. 35, ln. 4-9 that the VEGF antibody provided therein is derived from bevacizumab; and the benefit of reduced dose and/or frequency of administration at pg. 44, ln. 3-5; and less toxicity at pg. 43, ln. 30-33. Baehner et al. provide the VEGF antibody comprising SEQ ID NOs: 23 and 24. Baehner et al. disclose that antibodies comprising the sequences have improved characteristics such as biological or pharmacological activity, pharmacokinetic properties, toxicity, and show increased in vivo tumor growth inhibition at pg. 42, ln. 21-24. An alignment of Baehner et al. SEQ ID NOs: 23 and 24 to instant SEQ ID NOs: 88 and 89 is presented at the end of this section for Applicant’s convenience.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to substitute the VEGF antibody of Baehner et al. into the trispecific antagonist of Sheng et al. and Oliner et al. because Sheng et al. suggest that bevacizumab or another anti-VEGF antibody will work with the invention; Sheng et al. intend the trispecific antagonist to be used in cancer context; and Sheng et al. also teach the desired benefit of the invention of lower doses and toxicity. Baehner et al. teach an alternative VEGF antibody in similar bispecific format and the same desired benefits of lower doses and toxicity. Bahner et al. also discuss additional advantages of antibodies comprising the VEGF antibody such as improved biological or pharmacological activity, pharmacokinetic properties, toxicity, and inhibition of tumor growth. One of ordinary skill in the art would be motivated to use the VEGF antibody of Baehner et al. in the trispecific antagonist of Sheng et al. and Oliner et al. because Baehner et al. teach that the disclosed VEGF antibody will reduce toxicity, which is a same goal of Sheng et al., and in cancer context. Baehner et al. also teach the additional advantages of: reduced frequency of administration needed, improved biological or pharmacological activity, improved pharmacokinetic properties, and improved inhibition of tumor growth.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." The combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine the prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Accordingly, Sheng et al. in view of Oliner et al., and further in view of Baehner et al., renders claims 11-19 obvious.
ALIGNMENT TO INSTANT SEQ ID NO: 2:
Query Match 100.0%; Score 310; Length 285;
Best Local Similarity 100.0%;
Matches 52; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSATHQEECEWDPWTCEHM 52
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 AQQEECEWDPWTCEHMGSGSATGGSGSTASSGSGSATHQEECEWDPWTCEHM 192
US-16-845-924-209
Filing date in PALM: 2020-04-10
Sequence 209, US/16845924
Publication No. US20200277388A1
GENERAL INFORMATION
APPLICANT: GENSUN BIOPHARMA INC.
TITLE OF INVENTION: TRISPECIFIC ANTAGONISTS
FILE REFERENCE: 2022-003 US1-CONT
CURRENT APPLICATION NUMBER: US/16/845,924
CURRENT FILING DATE: 2020-04-10
PRIOR APPLICATION NUMBER: 16/457,343
PRIOR FILING DATE: 2019-06-28
PRIOR APPLICATION NUMBER: US 62/691,658
PRIOR FILING DATE: 2018-06-29
PRIOR APPLICATION NUMBER: US 62/823,989
PRIOR FILING DATE: 2019-03-26
NUMBER OF SEQ ID NOS: 420
SEQ ID NO 209
LENGTH: 285
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
ALIGNMENT TO INSTANT SEQ ID NO: 90:
Query Match 100.0%; Score 627; Length 117;
Best Local Similarity 100.0%;
Matches 117; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGWIFPGSGNSKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQGLEWMGWIFPGSGNSKY 60
Qy 61 NENFKGRVTLTADTSTSTVYMELSSLRSEDTAVYYCASETYDYGDYWGQGTLVTVSS 117
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NENFKGRVTLTADTSTSTVYMELSSLRSEDTAVYYCASETYDYGDYWGQGTLVTVSS 117
US-16-845-924-137
Filing date in PALM: 2020-04-10
Sequence 137, US/16845924
Publication No. US20200277388A1
GENERAL INFORMATION
APPLICANT: GENSUN BIOPHARMA INC.
TITLE OF INVENTION: TRISPECIFIC ANTAGONISTS
FILE REFERENCE: 2022-003 US1-CONT
CURRENT APPLICATION NUMBER: US/16/845,924
CURRENT FILING DATE: 2020-04-10
PRIOR APPLICATION NUMBER: 16/457,343
PRIOR FILING DATE: 2019-06-28
PRIOR APPLICATION NUMBER: US 62/691,658
PRIOR FILING DATE: 2018-06-29
PRIOR APPLICATION NUMBER: US 62/823,989
PRIOR FILING DATE: 2019-03-26
NUMBER OF SEQ ID NOS: 420
SEQ ID NO 137
LENGTH: 117
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
ALIGNMENT TO INSTANT SEQ ID NO: 91:
Query Match 100.0%; Score 563; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSFLSASVGDRVTITCKASQNVGTNVAWYQQKPGKAPKALIYSASYRYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSFLSASVGDRVTITCKASQNVGTNVAWYQQKPGKAPKALIYSASYRYSGVPS 60
Qy 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQYYSYPYTFGQGTKLEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQYYSYPYTFGQGTKLEIK 107
US-16-845-924-138
Filing date in PALM: 2020-04-10
Sequence 138, US/16845924
Publication No. US20200277388A1
GENERAL INFORMATION
APPLICANT: GENSUN BIOPHARMA INC.
TITLE OF INVENTION: TRISPECIFIC ANTAGONISTS
FILE REFERENCE: 2022-003 US1-CONT
CURRENT APPLICATION NUMBER: US/16/845,924
CURRENT FILING DATE: 2020-04-10
PRIOR APPLICATION NUMBER: 16/457,343
PRIOR FILING DATE: 2019-06-28
PRIOR APPLICATION NUMBER: US 62/691,658
PRIOR FILING DATE: 2018-06-29
PRIOR APPLICATION NUMBER: US 62/823,989
PRIOR FILING DATE: 2019-03-26
NUMBER OF SEQ ID NOS: 420
SEQ ID NO 138
LENGTH: 107
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic
ALIGNMENT TO INSTANT SEQ ID NO: 6:
US-10-269-695-124
Sequence 124, US/10269695
Publication No. US20030229023A1
GENERAL INFORMATION
APPLICANT: OLINER, JONATHAN DANIEL
APPLICANT: MIN, HOSUNG
TITLE OF INVENTION: SPECIFIC BINDING AGENTS OF HUMAN ANGIOPOIETIN-2
FILE REFERENCE: A-801A
CURRENT APPLICATION NUMBER: US/10/269,695
CURRENT FILING DATE: 2002-10-10
PRIOR APPLICATION NUMBER: US 60/414,155
PRIOR FILING DATE: 2002-09-27
PRIOR APPLICATION NUMBER: US 60/328,624
PRIOR FILING DATE: 2001-10-11
NUMBER OF SEQ ID NOS: 359
SEQ ID NO 124
LENGTH: 22
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Polypeptide capable of binding to Ang-2
Query Match 100.0%; Score 116; Length 22;
Best Local Similarity 100.0%;
Matches 22; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TNFMPMDDLEQRLYEQFILQQG 22
||||||||||||||||||||||
Db 1 TNFMPMDDLEQRLYEQFILQQG 22
ALIGNMENT TO INSTANT SEQ ID NO: 88:
ID AXX95743 standard; protein; 120 AA.
XX
AC AXX95743;
XX
DT 10-JUN-2010 (first entry)
XX
DE Humanized anti-VEGF IgG1 mAb G6-31 variable heavy chain SEQ 23.
XX
KW G6-31; Immunoglobulin G1; VEGF protein; VEGF-A ligand;
KW angiogenesis inhibition; antibody; antibody production; antibody therapy;
KW bispecific antibody; cancer; cytostatic; heavy chain variable region;
KW humanized antibody; monoclonal antibody; neoplasm; therapeutic;
KW tumor suppressor; vascular disease; vascular endothelial growth factor;
KW vasotropic.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN WO2010040508-A1.
XX
CC PD 15-APR-2010.
XX
CC PF 07-OCT-2009; 2009WO-EP007182.
XX
PR 08-OCT-2008; 2008EP-00017607.
PR 16-DEC-2008; 2008EP-00021834.
XX
CC PA (HOFF ) HOFFMANN LA ROCHE & CO AG F.
XX
CC PI Baehner M, Brinkmann U, Georges G, Griep RA, Imhof-Jung S;
CC PI Kavlie A, Kettenberger H, Klein C, Regula JT, Schanzer JM;
CC PI Schefer W, Scheuer W, Seeber S, Thomas M;
XX
DR WPI; 2010-E33083/28.
XX
CC PT New bispecific antibody specifically binds to human vascular endothelial
CC PT growth factor and human angiopoietin-2, useful as a pharmaceutical
CC PT composition or for manufacturing a medicament for treating cancer or
CC PT vascular diseases in a patient.
XX
CC PS Disclosure; SEQ ID NO 23; 147pp; English.
XX
CC The present invention relates to a novel bispecific antibody (Ab)
CC specifically binding to human vascular endothelial growth factor
CC (VEGF/VEGF-A) and human angiopoietin-2 (ANG-2). The novel novel
CC bispecific antibody comprises a first antigen-binding site that
CC specifically binds to human VEGF and a second antigen-binding site that
CC specifically binds to human ANG-2. Also claimed are: (1) a nucleic acid
CC encoding the bispecific antibody; (2) an expression vector containing the
CC nucleic acid capable of expressing the nucleic acid in a prokaryotic or
CC eukaryotic host cell; (3) a prokaryotic or eukaryotic host cell
CC comprising the vector; and (4) a method for the production of the
CC bispecific antibody, pharmaceutical compositions containing the
CC bispecific antibody, and uses thereof. The bispecific antibody is useful
CC as a pharmaceutical composition or in the manufacture of a medicament for
CC the treatment of cancer or vascular diseases in a patient. The bispecific
CC antibodies against human VEGF and human ANG-2 have improved
CC characteristics such as biological or pharmacological activity,
CC pharmacokinetic properties or toxicity. It shows increased in vivo tumor
CC growth inhibition and/or inhibition of tumor angiogenesis when compared
CC to the monospecific parent antibodies against VEGF and ANG-2. The present
CC sequence represents a human phage display derived humanized anti-VEGF
CC monoclonal antibody (mAb) G6-31 heavy chain variable region, a high-
CC affinity antibody to both murine and human VEGF-A, which was useful
CC during the invention for the preparation of a bispecific antibody against
CC human VEGF and against human ANG-2.
XX
SQ Sequence 120 AA;
Query Match 100.0%; Score 641; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTISDYWIHWVRQAPGKGLEWVAGITPAGGYTYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTISDYWIHWVRQAPGKGLEWVAGITPAGGYTYY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFVFFLPYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFVFFLPYAMDYWGQGTLVTVSS 120
ALIGNMENT TO INSTANT SEQ ID NO: 89:
ID AXX95744 standard; protein; 107 AA.
XX
AC AXX95744;
XX
DT 10-JUN-2010 (first entry)
XX
DE Humanized anti-VEGF IgG1 mAb G6-31 variable light chain SEQ 24.
XX
KW G6-31; Immunoglobulin G1; VEGF protein; VEGF-A ligand;
KW angiogenesis inhibition; antibody; antibody production; antibody therapy;
KW bispecific antibody; cancer; cytostatic; humanized antibody;
KW light chain variable region; monoclonal antibody; neoplasm; therapeutic;
KW tumor suppressor; vascular disease; vascular endothelial growth factor;
KW vasotropic.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN WO2010040508-A1.
XX
CC PD 15-APR-2010.
XX
CC PF 07-OCT-2009; 2009WO-EP007182.
XX
PR 08-OCT-2008; 2008EP-00017607.
PR 16-DEC-2008; 2008EP-00021834.
XX
CC PA (HOFF ) HOFFMANN LA ROCHE & CO AG F.
XX
CC PI Baehner M, Brinkmann U, Georges G, Griep RA, Imhof-Jung S;
CC PI Kavlie A, Kettenberger H, Klein C, Regula JT, Schanzer JM;
CC PI Schefer W, Scheuer W, Seeber S, Thomas M;
XX
DR WPI; 2010-E33083/28.
XX
CC PT New bispecific antibody specifically binds to human vascular endothelial
CC PT growth factor and human angiopoietin-2, useful as a pharmaceutical
CC PT composition or for manufacturing a medicament for treating cancer or
CC PT vascular diseases in a patient.
XX
CC PS Disclosure; SEQ ID NO 24; 147pp; English.
XX
CC The present invention relates to a novel bispecific antibody (Ab)
CC specifically binding to human vascular endothelial growth factor
CC (VEGF/VEGF-A) and human angiopoietin-2 (ANG-2). The novel novel
CC bispecific antibody comprises a first antigen-binding site that
CC specifically binds to human VEGF and a second antigen-binding site that
CC specifically binds to human ANG-2. Also claimed are: (1) a nucleic acid
CC encoding the bispecific antibody; (2) an expression vector containing the
CC nucleic acid capable of expressing the nucleic acid in a prokaryotic or
CC eukaryotic host cell; (3) a prokaryotic or eukaryotic host cell
CC comprising the vector; and (4) a method for the production of the
CC bispecific antibody, pharmaceutical compositions containing the
CC bispecific antibody, and uses thereof. The bispecific antibody is useful
CC as a pharmaceutical composition or in the manufacture of a medicament for
CC the treatment of cancer or vascular diseases in a patient. The bispecific
CC antibodies against human VEGF and human ANG-2 have improved
CC characteristics such as biological or pharmacological activity,
CC pharmacokinetic properties or toxicity. It shows increased in vivo tumor
CC growth inhibition and/or inhibition of tumor angiogenesis when compared
CC to the monospecific parent antibodies against VEGF and ANG-2. The present
CC sequence represents a human phage display derived humanized anti-VEGF
CC monoclonal antibody (mAb) G6-31 light chain variable region, a high-
CC affinity antibody to both murine and human VEGF-A, which was useful
CC during the invention for the preparation of a bispecific antibody against
CC human VEGF and against human ANG-2.
XX
SQ Sequence 107 AA;
Query Match 100.0%; Score 555; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQGYGNPFTFGQGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQGYGNPFTFGQGTKVEIK 107
Conclusion
13. No claim is allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON R SCHWECHTER whose telephone number is (571)272-1270. The examiner can normally be reached M-Th 7-5 EST.
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, Vanessa Ford can be reached at 20857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRANDON R SCHWECHTER/
Examiner, Art Unit 1674
/VANESSA L. FORD/ Supervisory Patent Examiner, Art Unit 1674
Prosecution Insights