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 .
DETAILED ACTION
Status of Application, Amendments, and/or Claims
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 amendment filed on 08/03/2026 has been entered.
New claims 21-26 are added. Claims 1, 3-4, 7, and 9-26 are pending. Claims 1, 3-4, 7, 9-12, and 21-26 are currently under consideration. Claims 13-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Withdrawn Objections and/or Rejections
The rejection of claims 1, 3-4, 7, and 9-12 under 35 U.S.C. 112(b) is withdrawn in view of the amended claims.
The objection to claim12 is withdrawn in view of the amended claim.
Information Disclosure Statement
The information disclosure statement filed on 02/27/2026 and 04/03/2026 has been considered by the Examiner and an initialed copy of the form PTO-1449 is attached to this communication.
Claim Rejections under 35 USC § 112 (a)
(i). The following is a quotation of the first paragraph of 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.
(ii). Claims 1, 3-4, 7, 9-12, and 21-26 are rejected under 35 U.S.C. 112(a), 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 at the time the application was filed, had possession of the claimed invention.
Claims 1, 3-4, 7, 9-12, and 21-26 are drawn to method to increase the functional copy number of a target antigen on the cell surface of a cell of a human subject, wherein the antigen is folate receptor alpha (FRα), comprising administering, to the human subject, a set of immunotherapeutic agents that target FRα, wherein the set of immunotherapeutic agents comprises a first immunotherapeutic agent comprising a first monoclonal antibody or antigen-binding fragment thereof conjugated with a first payload; at least one second immunotherapeutic agent comprising a second monoclonal antibody or antigen-binding fragment thereof conjugated with a second payload, wherein the first monoclonal antibody comprises a heavy chain variable region (VH) having an amino acid sequence at least 90 percent identical to the amino acid sequence of SEQ ID NO: 3 and a light chain variable region (VL) having an amino acid sequence at least 90 percent identical to the amino acid sequence of SEQ ID NO: 4; the second monoclonal antibody comprises a heavy chain variable region (VH) having an amino acid sequence at least 70 percent identical to the amino acid sequence of SEQ ID NO: 38, 39, or 40, and a light chain variable region (VL) having an amino acid sequence at least 70 percent identical to the amino acid sequence of SEQ ID NO: 41, 42, 43, or 44; wherein the first monoclonal antibody and the second monoclonal antibody are different and each binds human FRα, wherein the first monoclonal antibody binds a first B-cell epitope of FRα and the second monoclonal antibody binds a second B-cell epitope of FRα that is distinct and non-overlapping with the first B-cell epitope, wherein the first payload and the second payload are the same or different, and wherein the increase in the functional copy number comprises increasing the number of antibody-payload conjugates bound per FRα molecule without increasing the expression level of FRα on the cell surface. Thus, the claims recite a genus of first monoclonal antibodies comprising a VH and a VL having at least 90% sequence identity to SEQ ID NO: 3 and SEQ ID NO: 4, respectively, and a genus of the second monoclonal antibodies comprising a VH having at least 70% sequence identity to SEQ ID NOs: 38, 39, or 40, and a VL having at least 70% sequence identity to SEQ ID Nos: 41, 42, 43, or 44. The claims do not require that the first monoclonal antibody and the second antibody possess a set of six intact CDRs.
For each claim drawn to a genus, MPEP §2163 II.A.3(a) ii) (page 2100-189) states, “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 the instant case, the specification discloses pairs of human FRα antibodies that bind to non-overlapping B-cell epitopes on the human FRα. The specification discloses that the four secondary antibodies, MED019-008-007, MED019-008-033, MED019-008-051, and MED019-008-086 antibodies, bind to an epitope that does not overlap with the epitope bound by the primary antibody, A070 (page 68, paragraph [0179]; Table 25, Figure 8). However, without reciting the six intact CDRs, the instant disclosure does not provide sufficient support for the genus of the first antibodies, the second antibodies, and the non-overlapping epitopes, and thus the genus of the first immunotherapeutic agents and the second immunotherapeutic agents.
It is well established in the art that the formation of an intact antigen binding site of an antibody routinely requires the association of the complete heavy and light chain variable regions of a given antibody. It is expected that proper association of heavy and light chain variable regions is required in order to form a functional antigen binding site (Paul, Fundamental Immunology, 3rd Edition, 1993, pages 292-295; in particular page 293, column 1, lines 3-8; column 1, line 31 to column 2, line 9; column 2, lines 27-30). Vajdos et al. teach that amino acid sequence and conformation of each of the CDRs of the heavy and light chains is critical for maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (J. Mal. Biol. 320:415-428, 2002; in particular page 416).
Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other anti-human FRα antibodies might be. The sequence search does not reveal a genus of the first anti-human FRα monoclonal antibodies and a genus of the second anti-human FRα monoclonal antibodies that meet the percent sequence homology recited in the instant claims.
For the reasons above, claims 1, 3-4, 7, 9-12, and 21-26 are rejected.
(iii). Response to Applicant’s argument
Applicant argues that claim 1 as currently amended recites a genus of anti-FRa antibodies structurally anchored to specific reference sequences disclosed in the specification: the VH and VL sequences of the first monoclonal antibody are each at least 90 percent identical to the VH and VL sequences of the A070 antibody disclosed in the specification as filed (see Tables 1-2; see also Example 2 describing binding of A070 to human FRa extracellular domain (paragraphs [0162]-[0163]); Example 5 describing binding of A070 to FRa expressed on cells (paragraph [0171])); and the VH and VL sequences of the second monoclonal antibody are each at least 70 percent identical to the VH and VL sequences of the secondary antibodies MED019-008-007, MED019-008-033, MED019-008-051, and MED019-008-086 disclosed in the specification (Tables 15-16), which are described as binding human FRa with high affinity (see Example 6; Table 26; paragraph [0179]). The specification further fully supports that these secondary antibodies bind a B-cell epitope that does not overlap with the epitope bound by A070 (see Example 6; Table 25; paragraph [0179]). Accordingly, the specification reasonably conveys to a person of ordinary skill in the art that the inventors were in possession of the claimed genus as of the filing date. Applicant’s argument has been fully considered but is not deemed to be persuasive for the reasons set forth in the rejection above.
Conclusion
No claims are allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ruixiang Li whose telephone number is (571) 272-0875. The examiner can normally be reached on Monday through Friday from 8:30 am to 5:00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached on (571) 272-0857. The fax number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/RUIXIANG LI/Primary Examiner, Art Unit 1674 August 7, 2026
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