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
Applicant's amendment filed on 05/19/2026 has been entered. New claims 27-30 are added. Claims 1, 7-8, 10-11, 14, 23, and 25-30 are pending. Claims 1, 7-8, 10, and 23, 25-30 are currently under consideration. Claims 11 and 14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
The declaration of Dr. Amit Sachdeva filed on 05/19/2026 under 37 C.F.R §1.132 has been received and considered.
Withdrawn Objections and/or Rejections
The rejections of claims 3-4 and 24 under 35 U.S.C. 112(a) is made moot by cancellation of the claims.
The rejection of claims 4, 23 and 26 under 35 U.S.C. 112(b) is withdrawn in view of amended claims.
The rejection of claims 1, 3, 7, 10, and 23 under 35 U.S.C. 103 as being unpatentable over WO 2007/107764 A1 in view of WO 9713782 A1 are withdrawn in view of amended claims.
Information Disclosure Statement
The information disclosure statement filed on 05/19/2026 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, 7-8, 10, 23, and 25-30 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. The basis for the rejection is set forth in the office action mailed on 11/19/2025.
(iii). Response to Applicant’s argument
Applicant presents a declaration of Dr. Amit Sachdeva under 37 C.F.R §1.132, which is filed on 05/19/2026. In the declaration, Dr. Sachdeva states that the VHH antibody fragments of claim 1 as amended (and claims dependent on claim 1) have the same conserved structure due to 1) the restriction to a single antibody fragment type, namely VHH, 2) the requirement that the photocaged amino acid is a tyrosine residue. Therefore, the photocaged antibodies have specific structural/functional features (#9). Dr. Sachdeva states that tyrosine amino acids are commonly present in antibody CDRs in VHH antibody fragments (#10 and #11, Exhibits 1-3). Dr. Sachdeva further states that it is thought that this is due to tyrosine residues being particularly well suited for making productive (hydrophobic and hydrogen bonds) contacts with antigen (#12, Exhibit 4).
Applicant argues that claim 1 has been amended to refer to a VHH antibody fragment and specify that the photocaged amino acid is a photocaged tyrosine residue. Applicant argues that the photocaged antibodies have specific structural/functional features. Referring to the declaration of Dr. Amit Sachdeva, Applicant argues that tyrosine amino acids are commonly present in antibody CDRs and that amended claim 1 has sufficient written description. Applicant argues that the inventors have developed a method of photocaging antibodies, wherein the antibody is conditionally active in the presence of light. The claims define a specific antibody fragment and require that the photocaged amino acid is a photocaged tyrosine residue. Applicant argues that this is commensurate with the examples and that it is clear that the inventors were in possession of the invention at the time the application was filed.
The declaration of Dr. Amit Sachdeva under 37 C.F.R §1.132 filed on 05/19/2026 has been considered but is insufficient to overcome the rejection. Applicant’s argument has been fully considered but is not deemed to be persuasive. 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, claim 1 is drawn to a VHH antibody fragment wherein said VHH antibody fragment comprises a photocaged amino acid in a complementarity determining region (CDR) of its antigen binding region, wherein i) the photocaged amino acid comprises a light-removable protection group comprising an o-nitrobenzyl functional group; ii) the photocaged amino acid is present at a site in which the photocaged amino acid inhibits binding of the antibody to its antigen, wherein binding of the antibody to its antigen can be induced upon activation with a light source; iii) the photocaged amino acid is a photocaged tyrosine residue; and iv) the VHH antibody fragment is conjugated to another moiety, wherein said moiety is selected from a half-life extension moiety, a label, and a toxic moiety. Claim 1 and its dependent claims do not require that the VHH antibody fragment possess any particular conserved structure, functional feature, nor other disclosed distinguishing feature. It is noted that recitation of a general class molecule, a VHH antibody fragment, wherein said VHH antibody fragment comprises a photocaged tyrosine residue in a complementarity determining region (CDR) of its antigen binding region, does not represent a specific structural feature because it does not define the structure of a VHH antibody fragment.
The specification discloses a site-specific incorporation of o-nitrobenzyl (photocaging) group at a tyrosine residue into 7D12 (Example 1). The specification discloses that the presence of a photocaging group at a specific tyrosine residue (pcY32 or pcY113) in the antigen binding region of 7D12 inhibits its binding to EGFR and the binding is restored upon irradiation with 365 nm light (Examples 2-3). In contrast, the presence of a photocaging group at a specific tyrosine residue (pcY109) in the antigen binding region of 7D12 does not inhibit its binding to EGFR (paragraph [0164]), indicating the fact that it is unpredictable whether the presence of photocaging group at a given tyrosine residue inhibits binding of the antibody to its antigen.
Furthermore, there is no disclosure of the presence of a photocaging group at any other positions in the CDR of the antigen binding region of 7D12; there is no disclosure of any other antibodies with photocaged tyrosine residues; A disclosure of a single photocaged anti-EGFR antibody 7D12 in two tyrosine residues (pcY32 or pcY113) is insufficient to support the broad genus of claimed VHH antibody fragments.
Finally, 35 U.S.C. 112(a) requires that Applicant was in procession of the claimed subjection at the time the application was filed. Experimental steps that are required to identify the residues necessary for the introduction of a photocaged group in an antibody do not show that Applicant was in possession of the instantly claimed photoactive antibodies. Accordingly, due to the breadth of the genus of the photoactive antibodies and lack of the definitive structural/functional features of the genus, one skilled in the art would not recognize from the disclosure that Applicant was in possession of the genus of the claimed photoactive VHH antibody fragments.
Conclusion
No claims are allowed.
Advisory Information
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 extension fee 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 date of this final action.
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 May 27, 2026
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