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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 submission filed on 11/10/2025 has been entered.
Claims 1, 3-4, 7-8, 10-11, 14, and 23-26 are pending. Claims 1, 3-4, 7-8, 10, and 23-26 are currently under consideration. Amended claims 11 and 14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.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 under 37 C.F.R §1.132 has been received and considered.
Withdrawn Objections and/or Rejections
The rejection of claims 1-4, 7-8, 10, and 23-25 under 35 U.S.C. 112(b) is withdrawn in view of amended claim 1.
The objection to claim 10 is withdrawn in view of amended claim 10.
Information Disclosure Statement
The information disclosure statement filed on 11/10/2025 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, 7-8, 10, and 23-26 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.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claim 1 is drawn to an antibody or fragment thereof wherein said antibody or 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 interaction of the antibody to its antigen can be induced upon activation with a light source. Claim 1 and its dependent claims do not require that the antibody possess any particular conserved structure, functional feature, nor other disclosed distinguishing feature. Thus, the claims are drawn to a genus of photocaged antibodies without any structural/functional features.
The specification discloses a site-specific incorporation of o-nitrobenzyl (photocaging) group into 7D12 (Example 1). The specification discloses that the presence of a photocaging group at specific tyrosine residues (pcY32 and 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). The specification discloses that photoactive antibodies can mediate delivery of small molecule fluorophores to the surface of EGFR-positive live cancer cells in a light-dependent manner (Example 4). However, such a disclosure is insufficient to support the broad genus of photoactive antibodies.
Vas-Cath Inc. v Mahurkar, 19 USPQ2d 1111 (Fed. Cir.1991), 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 purpose 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). Adequate written description requires more than a mere statement that it is part of the invention are reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir.1991).
An adequate written description of a chemical invention “requires a precise definition, such as by structure, formula, chemical name, or physical properties." University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir.2004); Regents of the Univ. of Cal. V. Eli Lilly & Co., Inc., 119 F.3d 1559, 1556 (Fed. Cir.1997); Fiers v. Revel, 984F.2d 1164, 1171 (Fed. Cir.1993). “A description of what a material does, rather than of what it is, usually does not suffice.” Rochester, 358F.3d at 923; Eli Lilly, 119 F.3d at 1568. In addition, possession of a genus “may be achieved by means of a recitation of a representative number of [compounds]…falling within the scope of the genus.” Eli Lilly, 119 F.3d at 1569. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus. See Rochester, 358 f. 3d at 927. In the instant case, the disclosure of a photoactive antibody 7D12 does not provide adequate support for the instantly claimed antibodies.
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 photoactive antibodies.
Response to Applicant’s argument
The declaration of Dr. Amit Sachdeva under 37 C.F.R §1.132 has been considered and the issues related to the limitation “in a complementarity determining region (CDR) of its antigen binding region” recited in claim 1 has been resolved.
Applicant argues that the claims are limited to a common structure, the required presence of the o-nitrobenzyl functional group. Applicant also argue that the application provides examples of the experimental steps that are required to identify the residues necessary for the introduction of a phototocaged group in other antibodies.
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 an antibody or fragment thereof wherein said antibody or 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 interaction of the antibody to its antigen can be induced upon activation with a light source. Claim 1 and its dependent claims do not require that the antibody possess any particular conserved structure, functional feature, nor other disclosed distinguishing feature. 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). The specification discloses that photoactive antibodies can mediate delivery of small molecule fluorophores to the surface of EGFR-positive live cancer cells in a light-dependent manner (Example 4). However, there is no disclosure of the presence of a photocaging group at any other amino acid residues in the antigen binding region of 7D12; there is no disclosure of any other antibodies with photocaged amino acids; A disclosure of a single photocaged anti-EGFR antibody 7D12 is insufficient to support the broad genus of claimed photoactive antibodies.
Moreover, 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 antibodies.
Claim Rejections under 35 USC § 112 (b)
(i). The following is a quotation of the second paragraph of 35 U.S.C. 112:
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.
(ii). Claims 4, 23, and 26 are 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 or a joint inventor regards as the invention.
(a). Claim 4 recites “wherein the antibody or fragment thereof is conjugated to another moiety.” It is unclear what “another moiety” refers to, rendering the claim indefinite.
(b). A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 23 recites the broad recitation “a kit comprising the antibody or fragment thereof according to claim 1”, and the claim also recites “optionally comprising a LED wearable device or an LED implantable device”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Claim 26 is rejected on the same basis.
Claim Rejections under 35 USC § 103(a)
(i). The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
(ii). Claims 1, 3, 7, 10, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2007/107764 A1 in view of WO 9713782 A1.
WO 2007/107764 A1 teaches an antibody or fragment thereof comprising an antigen binding site specific for CD3 (a cell surface antigen) and capable of activating a T cell on binding to CD3, said antibody being reversibly inhibited from binding to CD3 by the presence of at least one photocleavable moiety (page 7, last paragraph; page 5, lines 26-28), such as o-nitrobenzyl (page 16, line 31). The antigen binding site will typically be inhibited from binding to the cell of the immune system by the presence of one or more blocking moieties coupled to the antibody via a selectively cleavable group or bond at the antigen binding site (page 6, 1st paragraph). The cleavable group or bond may be cleavable by irradiation (page 6, the 2nd paragraph). The antibody fragment includes Fab, a single chain Fv, dAb (page 5, lines 26-28; page 13, 4th paragraph). WO 2007/107764 A1 teaches a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable carrier (page 9, line 35 to page 10, line 2).
WO 2007/107764 does not teach explicitly an antibody or fragment there of comprising a photocaged amino acid in a complementarity determining region (CDR) of its antigen binding region
WO 9713782 A1 teaches a method of making a photosensitive biological molecule, which is applicable to a variety of class of compounds, including antibodies and antigens (page 9, the 3rd paragraph). The method utilizes photosensitive or photolabile protecting groups, i.e., caging groups, which are specifically engineered into the backbone of a biological molecule, as a means to inactivate or alter or modify the functional activity of the molecule upon exposure to the light (page 9, the 4th paragraph). Positioning of a caged amino acid as a means for modifying activity of a biological molecule is determined according to standard methods known in the art (page 10, the 2nd paragraph). The photoactive group includes an o-nitrobenzyl (2-nitrobenzyl) group (page 2, the 2nd paragraph).
It would have been obvious for one skilled in the art to make an antibody or fragment thereof wherein said antibody or fragment comprises a photocaged amino acid in a complementarity determining region (CDR) of its antigen binding region with a reasonable expectation of success. One would have been motivated to do so because the complementarity determining region (CDR) of the antigen binding site of an antibody is known in the art to be critical for the binding and functional activity of an antibody, whereas incorporation of a caged amino acid in the complementarity determining region (CDR) of the antigen binding site of an antibody would inactivate of the antibody upon exposure to light in view of the teachings of the cited art.
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 November 15, 2025