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 .
Election/Restrictions
Applicant’s election of Group 3 in the reply filed on 08/03/26 is acknowledged. Because applicant did not distinctly and specifically point out any supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Regarding the species election and applicant’s arguments, said species election is hereby withdrawn.
Claims 18-37 are pending.
Claims 18-28, and 37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 29-36 are pending and under consideration.
Information Disclosure Statement
The IDS filed 07/08/2026 has been considered. However, reference “US-2019083662 A1” was not considered as it appeared to be a typographical error. Instead, US 20190083662 (Burak et al.) was considered. 20230052140 (Burak et al.) was also considered instead of “US-2023052140 A1”. Also, see other references crossed out due to typographical errors and replaced by consideration of references in the PTO-892.
The IDS filed 03/06/2026 was considered. However, the reference by Finkelstein was not considered as no author by that name was in the file wrapper.
Claim Rejections - 35 USC § 102
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.
Claim(s) 29-30 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Eichmann et al. (US 20060153840A1, previously cited).
Eichmann et al. teach [0158, 0164] anti-netrin-1 antibodies or antigen binding fragments thereof for the treatment of patients having tumors [0016, 0265, 0271] including by intratumoral and peritumoral delivery [0253]. Eichmann et al. further teach [0200-0201, 0211, 0260] radiotherapy comprising immunoconjugates of the antibodies conjugated to radioactive isotopes such as 212Bi, 131I, and 90Y. The reference further teaches [0202] an exemplary chelating agent (MX-DTPA) for conjugation of radionucleotide to the antibody.
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.
Claims 29-33, and 36 are 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a Written Description Rejection.
The claims are broadly drawn to administering “an anti-Netrin-1 antibody” for the purposes of internal radiotherapy (Claim 29) or identifying and treating patients with a netrin-1 expressing cancer (Claims 31 and 33). Thus, the claims are broadly drawn to a genus of anti-netrin-1 antibodies for detecting and treating cancer.
Regarding possession of a genus of anti-nectrin antibodies, the specification teaches [0022-0023] one murine anti-nectrin antibody referred to as 4C11. The specification further teaches the anti-netrin HUM00 antibody which corresponds to the grafting of the murine 4C11 CDRs into a human IgG1. The specification further teaches 10 other monoclonal antibodies (HUM01-HUM10) which are derived from HUM00 with specific modifications in the framework regions (FR) of the human IgG. As noted by applicants in the response filed 08/03/2026, “the two sets of CDRs recited in claims 20, 34, and 37 correspond to the same CDRs, merely defined according to two different numbering/classification systems, namely the Kabat and IMGT”. Thus, it would appear that applicants are only in possession of an anti-netrin antibody comprising the two sets of CDRS recited in claims 34. The specification further refers to [0044] other commercially available antibodies such as ab126729, ab122903, ab201324, ab39370; AF1109, AF6419, AFR 28. However, a search and review of the cited Abcam products by Google AI revealed that the majority are polyclonal antibodies. One (ab39370) is no longer commercially available and AFR 28 typically refers to a reference reagent. However, the disclosure of 1 species of anti-netrin antibody with complete CDRs or one commercial (ab126729) anti-netrin antibody does not provide sufficient evidence of possession to the full genus of claimed antibodies. A "representative number of species" means that the species which are adequately described are representative of the entire genus. The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, inventor was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). For example, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties). Thus, the written description is not commensurate in scope to a genus of anti-Netrin-antibodies. Applicants have only sufficiently provided a written description for one anti-netrin antibody comprising the HCDRs of SEQ ID NO:1-3 (or SEQ ID NOs: 22-24) and the LCDRs of SEQ ID NO:4, (YAS) and SEQ ID NO:5 (or SEQ ID NOs: 25-26, and 5) as presented in claim 34.
Sela-Culang, Kunik, and Ofran (Fron. Immuno., Vol. 4, Article 302, Oct. 2013), hereinafter “Sela-Culang”, reviews the structural basis of antibody-antigen recognition in the state of the art. Naturally occurring antibodies typically consists of four polypeptide chains with two identical heavy (H) and two identical light (L) chains, with H and L chains liked to form a Y-shaped structure known as a Fab [e.g., pg. 4, Figure 2A-B]. The Fab has two variable (V) domains (VH and VL) that dimerize to form the Fv fragment which comprises the antigen-binding site of the antibody via six hypervariable loops (3 Heavy, 3 light) [e.g., pg. 3, “The Role of CDRs and their Definition”]. The six hypervariable loops are commonly termed complementary determining regions (CDRs) and are widely assumed to be responsible for antigen recognition [e.g., pg. 1, abstract] and the three-dimensional configuration of these CDRs form the antigen-recognition complex termed a paratope [e.g., pg. 3, “The Role of CDRs and their Definition”]. Despite the integrated effect of CDRs, antibodies can also be considered a modular system, composed of different elements (e.g., Fab, VH, VL) which may bind to an antigen on their own with the smaller fragments retaining affinity and specificity, which is of great potential for drug design [e.g., pg. 6, paragraph 2]. A person of ordinary skill in the art would understand that although the above basics of antibody-antigen binding are known, that the specifics of antibody structure (e.g., within the CDRs) that underlie the antigen recognition are not well characterized [e.g., pg. 1, “The Motivations for…”].
Further, Herold et al. (Nature Scientific Reports, 7:12276, 25 Sep 2017), hereinafter “Herold”, teaches that it should be emphasized that there is no correlation between experimentally determined change in antibody binding affinity and a given mutation and additionally that no such correlation is expected because antigen binding is “affected by each CDR loop differently” and changes thereto “can in principle affect antigen binding affinity in an unpredictable way” [e.g., pg. 14, paragraph 2]. Further, Herold asserts that multiple determinants regulate antigen affinity and the interactions with CDRs are complex [e.g., pg. 14, paragraph 3]. Herold further teaches that variable heavy chain (VH) mutations led to a decrease in binding affinity, with as much as 20-fold higher KD in the mutant versus wild type [e.g., pg. 4, paragraph 3], and summarizes the antigen binding KD differences based on point mutations in the VH or VL of an IgG antibody [e.g., pg. 6, table 1].
As indicated by the art, a full complement of 6 CDRs are required for antigen binding and one cannot predict which CDR residues may be changed and still result in an antibody that binds netrin-1. Written description can be met if the claims recite the minimal structure that is needed to perform the function recited in the claims. Above, the art indicates that the 6 CDRs in an antibody are the minimal structure that binds to a target antigen.
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.
Claims 31-36 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.
Claim 31 is rejected as vague for reciting “obtaining binding” in step b as it is not clear what the active step of obtaining the binding encompasses. The general definition of obtain means to gain possession of something tangible or intangible. The specification teaches [0097] that in PET, the standard uptake value may be calculated allowing one to obtain quantification of the tracer in an observed area. However, as written, the currently claimed “obtained binding” does not afford the same details as the specification, and it’s not clear if “obtaining binding” means something different. In other words, what does a person of skill in these arts do by “obtaining binding”?
No claim is currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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