Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
FINAL ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/3/25 has been entered.
Amendment Entry
2. Applicant’s response to the Final Action dated 6/3/25 is acknowledged (paper filed 9/3/25). In the amendment filed therein claims 84, 91, 94, 96, and 101 were modified. While claims 1-83, 85, 89, 90, and 109-113 were cancelled without prejudice or disclaimer. Currently, claims 84, 86, 106, 114-116, and 148 are pending.
3. Objections and/or rejections of record not reiterated herein have been withdrawn.
Priority
4. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119 (e) or under 35 U.S.C. 120, 121, or 365 (c) is acknowledged. The application claims benefit to provisional application no. 63/299,177 filed 1/13/22, provisional application no. 63/310,359 filed 2/15/22, and provisional application no. 63/335,805 filed 4/28/22.
5. The application has been given a priority date of January 13, 2022.
Information Disclosure Statement
6. The listing of references in the specification 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 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the Examiner on form PTO-892 or Applicant on PTO-1449 cited the references they have not been considered.
7. The information disclosure statement filed on 9/3/25 has been considered as to the merits before FINAL action.
NEW GROUNDS OF REJECTIONS NECESSITATED BY AMENDMENTS
Election/Restriction
8. Applicant’s elected Group I (claims 84-108) without traverse in the reply filed on 8/6/24. Applicant has also elected Species VH-SEQ ID NO:18 and VL-SEQ ID NO:19. in the reply filed on 8/6/24.
9. Claims 87-105, 107, 108, and 117-147 are previously withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
10. Applicant has amended withdrawn claims 91-101 to depend on claim 84. Additionally, Applicant has requested Rejoinder of the withdrawn claims and argues that claims 87, 88, 91-105, 107, 108, and 117-147 are also directed to the elected Group I invention and encompass the elected species of SEQ ID NOs: 18 and 19.
Response to Arguments
The request for rejoinder has been carefully considered but was not found persuasive for the following reasons:
A. Restriction is not only based on claim dependency but inventive concept.
B. The invention of withdrawn claims 87, 88, 91-105, 107, 108, and 117-147 are drawn to a plurality of disclosed patentably distinct peptide/nuclei acid inventions comprising materially different amino acid and/or nucleic acid compositions as evidence by separate SEQ ID Nos (sequence identification numbers). These separate peptides/nucleic acids bear distinct structural or biochemical properties as substantiated by the separate SEQ ID Nos; therein comprising diverse composition configurations. Each disclosed patentably distinct peptide or nucleic acid sequence is considered a separate invention.
C. It is recognized that although the search for the inventions may overlap they are not totally co-extensive, where the search for one would fully encompass the search for the others. Because these inventions are distinct due at least in part by the separate and distinct sequence identification numbers, the search required for all the claimed inventions are not mutually inclusive (i.e. the search for one invention encompasses in totality the search for the other inventions) and restriction for examination purposes as indicated is proper.
Examination will be restricted to only the elected sequences (SEQ ID Nos 18 and 19).
Claim Rejections - 35 USC § 112
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.
11. Claims 114-116 and 148 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A. Claims 114-116 and 148 remain vague and indefinite in reciting that the fusion protein comprises a VEGF receptor extracellular domain without identifying the structure (sequence identification number). This makes the fusion construct ambiguous. It is suggested that the entire composition is identified by the appropriate sequence or binding composition in order to obviate this rejection.
Response to Arguments
Applicant argues that independent claim 114 recites “means for binding VEGF”. Therefore claim 114 is a “means-plus-function” limitation and it does not have a sufficiently definite meaning as the name or structure is understood by persons of ordinary skill in the art. See Willam son v. Citrix Online, LLC., 792 F.3d 1339, 1348 (Fed. Circ. 2015). Thus, claim 114 invokes 35 U.S.C. § 112(f). And “The proper test for meeting the definiteness requirement is that the corresponding structure (or material or acts) of a means- (or step-) plus-function limitation must be disclosed in the specification itself in a way that one skilled in the art will understand what structure (or material or acts) will perform the recited function.” M.P.E.P. § 2181.IL.A (citing Atmel Corp. v. Information Storage Devices, Inc., 198 F.3d 1374, 1381 (Fed. Cir. 1999)).
This argument was carefully considered but not found persuasive because the specification is limited to only SEQ ID NO:13 and SEQ ID NO:14. See paragraph [0129] of the instant specification wherein “the VEGF-binding domain comprising a vascular endothelial growth factor (VEGF)-A binding region of VEGF receptor 1 (VEGFR1) of SEQ ID NO: 13 and a vascular endothelial growth factor (VEGF)-A binding region of VEGF receptor 2 (VEGFR2) of SEQ ID NO: 14.” Therefore, the specification does not provide for the infinite possible means of binding VEGF. One skilled in the art reading the disclosure would only understand SEQ ID NO:13 and SEQ ID NO:14 as the indicated “means for” determining what structure (or material or acts) will perform the recited function.
Sequence identification numbers 13 and 14 are not included in the claims. Accordingly, the claims remain indefinite.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
12. Claims 114-116 and 148 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an anti-Tie2/VEGF bivalent bispecific antibody wherein the VEGF domain comprises SEQ ID NOS 13, 14, or 15 (see sections 0016, 0023, 00129 of the disclosure), does not reasonably provide enablement for any and all ant-Tie2/VEGF bivalent, bispecific antibodies. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Claims 114-116 and 148 are drawn to fusion proteins comprising:
Claim 114. A fusion protein comprising an anti-Tie2 antibody and a means for binding VEGF, wherein the anti-Tie2 antibody comprises a VH and a VL.
However the only example of an operable construct as claimed is demonstrated with an VEGF component of SEQ ID NOS: 13, 14, and 15 (see disclosure sections 0016, 0023, and 00129 for example).
Therefore the claimed method is not enabled for an anti-Tie2 antibody-VEGF bivalent bispecific antibody fusion product as claimed.
The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116). The court indicated that while Applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a representative number of molecules falling within the scope of the claimed genus. Therefore the full breadth of the claims, reading on any and all "bivalent, bispecific antibody” are not commensurate in scope with the claimed method.
The following rejection is made in consideration of the recent U.S. Court of Appeals for the Federal Circuit decision in Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017):
13. Claims 114-116 and 148 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed to any and all fusion proteins comprising an anti-Tie2 antibody and VEGF receptor extracellular domain comprising a bivalent, bispecific antibody and antigens specific thereto. However, the disclosure does not appear to teach antibodies that have been characterized (known binding sites -sequences) or deposited.
Recently, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies.
In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
MPEP 2163 provides the “Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, “Written Description” Requirement)”. More particularly, MPEP Section 3(ii) states that:
For each claim drawn to a genus:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
In this case, the specification lacks complete deposit information for the deposit of hybridoma cell lines and antibodies in accordance with 37 CFR1.801-1.809. While the specification provides enough information for one ordinary skill in the art to produce hybridoma cell lines and antibodies the reproduction of identical cell lines and antibodies is an extremely unpredictable event.
Because it does not appear that the antibodies and their corresponding hybridoma cell lines, are known and publicly available or can be reproducibly isolated from nature without undue experimentation, a suitable deposit of the hybridoma cell lines and antibodies for patent purposes is required. It is not clear from the disclosure that the bivalent bispecific antibodies are commercially available.
If the deposits have not been made under the provisions of the Budapest Treaty, then in order to certify that the deposits comply with the criteria set forth in 37 CFR § § 1.801-1.809, assurances regarding availability and permanency of deposits are required.
Such assurance may be in the form of an affidavit or declaration by applicants, assignees or a statement by an attorney of record over his or her signature and registration number stating that the deposit has been accepted by an International Depository Authority under the provisions of the Budapest Treaty, that all restrictions upon public access to the deposit will be irrevocably removed upon the grantof a patent on this application and that the deposit will be replaced if viable samples cannot be dispensed by the depository is required. This requirement is necessary when a deposit is made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State.
Amendment of the specification to recite the current practice requiring that a statement concerning all restrictions upon public access to the deposit will be irrevocably removed upon the grant of a patent on this Application and that the deposit will be replaced if viable samples cannot be dispensed by the depository made in the instant Application.
Without such a statement, it would be impossible for the skilled artisan to practice the invention of claims 114-116 and148 because the specific deposits cannot be placed into the hands of the artisan because other clones made from the source material have no predictable reasonable expectation of success of being identical to the single clone deposited.
Furthermore, unless the deposit was made at or before the time of filing, a declaration filed under 37 C.F.R. 1.132 is necessary to construct a chain of custody.
The declaration, executed by a person in a position to know should identify the deposited hybridomas and antibodies by its depository accession number, establishes that the deposited hybridomas and antibodies are the same as that described in the specification, and establish that the deposited hybridomas and antibodies were in applicants’ possession at the time of filing.
Applicant's attention is directed to In re Lundak, 773 F.2d. 1216, 27 USPQ 90 (CAFC1985) and 37 CRF §§ 1.801-1.809 for further information concerning deposit practice.
Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 1111, clearly states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116). Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC 112 is severable from its enablement provision (see page 115).
Without a deposit and removal of public restrictions, the skilled artisan cannot envision the detailed structure of the claimed antibody compositions, thus conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of production and or isolation.
An adequate description requires more than a mere statement that it is part of the invention and a reference to a potential method of isolating it.
The court indicated that while Applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a representative number of molecules falling within the scope of the claimed genus.
Therefore the full breadth of the claims, reading on the claimed "bivalent, bispecific antibody and its binding antigens does not meet the written description provision of 35 USC 112, first paragraph.
Response to Arguments
Applicant contends that independent claim 114 recites “means for binding VEGF”. Therefore claim 114 is a “means-plus-function” limitation and it does not have a sufficiently definite meaning as the name or structure is understood by persons of ordinary skill in the art. See Willam son v. Citrix Online, LLC., 792 F.3d 1339, 1348 (Fed. Circ. 2015). Thus, claim 114 invokes 35 U.S.C. § 112(f). And “The proper test for meeting the definiteness requirement is that the corresponding structure (or material or acts) of a means- (or step-) plus-function limitation must be disclosed in the specification itself in a way that one skilled in the art will understand what structure (or material or acts) will perform the recited function.” M.P.E.P. § 2181.IL.A (citing Atmel Corp. v. Information Storage Devices, Inc., 198 F.3d 1374, 1381 (Fed. Cir. 1999)).
This argument was carefully considered but not found persuasive because the specification is limited to only SEQ ID NO:13 and SEQ ID NO:14.
See paragraph [0129] of the instant specification wherein “the VEGF-binding domain comprising a vascular endothelial growth factor (VEGF)-A binding region of VEGF receptor 1 (VEGFR1) of SEQ ID NO: 13 and a vascular endothelial growth factor (VEGF)-A binding region of VEGF receptor 2 (VEGFR2) of SEQ ID NO: 14.” Therefore, the specification does not provide for the infinite possible means of binding VEGF. One skilled in the art reading the disclosure would only understand SEQ ID NO:13 and SEQ ID NO:14 as the indicated “means for” determining what structure (or material or acts) will perform the recited function.
Sequence identification numbers 13 and 14 are not included in the claims. Accordingly, the claims remain rejected under 35 USC 112(a).
Additionally, Applicant argues that the Office’s alleges that the claimed subject matter to “any and all fusion proteins comprising an anti-Tie2 antibody and VEGF receptor extracellular domain comprising a bivalent, bispecific antibody and antigens specific thereto” is incorrect with respect to the anti-Tie2 antibody. Independent claim 114 (from which the other claims subject to this rejection ultimately depend) recite that the VH and VL of this antibody comprise HCDR1-3 and LCDR1-3 sequences, respectively, comprising specified SEQ ID NOs. Thus, the claims specify structure for the CDRs of the anti-Tie2 antibody present in the fusion protein.
Applicant respectfully submits that Amgen v. Sanofi and the Office’s allegations regarding deposit requirements at pages 9-11 of the Office Action dated 6/3/25 do not apply to recitations of antibodies in which the six CDRs are recited.
This argument was not found persuasive because the claims include to binding entities anti-Tie2 and VEGF binding composition. While the configurations for anti-Tie2 have met the requirement under 35 USC 112(a), the binding constructs for VEGF have not. Accordingly, the rejections are maintained.
Allowable Subject Matter
14. Claims 84, 86, and 106 are allowed.
15. For reasons aforementioned, no claims are allowed.
16. All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LISA COOK whose telephone number is 571-272-0816. The examiner works a flexible schedule but can normally be reached on Monday-Friday from 9am to 5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, SAMIRA JEAN-LOUIS can be reached at telephone number 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Lisa V. Cook
Patent Examiner
Art Unit 1642
Remsen - Hoteling
571-272-0816
9/5/25
/LISA V COOK/Primary Examiner, Art Unit 1642