DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claims 1-13 are pending.
Applicants’ elections with traverse of (1) antibody 15A2 as the species of anti-B7H3 antibody, and (2) toxin as the species of conjugating part, in the reply filed on 8/5/26 are acknowledged. However, because no prior art has been identified that anticipates or renders obvious the claimed antibody species, the requirement for each election of species is herewith withdrawn, and the traversals are therefore moot.
Claims 1-13 are under consideration.
Specification
The disclosure is objected to because it contains an embedded hyperlink (browser-executable code) at ¶ 42 (page 10). Applicants are required to remove the embedded hyperlink; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01 (VII). Appropriate correction is required.
Claim Objections
Claims 1-13 are objected to because of the following informalities:
In claim 1, line 2, the acronym “CDR” should be accompanied by the full terminology the first time it is used in a series of claims, e.g., “complementarity-determining region (CDR)”.
In each of claims 6, 8, 12 and 13, “T lymphocyte” should be “T lymphocytes”.
The remaining claim(s) are objected to for depending from an objected claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a), written description
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 1 and 6-13 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicants are claiming and what Applicants have possession of.
Independent claim 1 is a product claim directed to anti-B7H3 monoclonal antibodies, or antigen-binding fragments thereof, and methods of using such. In independent claim 1, the antibody must comprise “a heavy chain CDR” and “a light chain CDR” selected from “one or more groups of CDR combinations denoted as a to n”. While each of the recited groups (a to n) includes six CDR sequences, the claim only requires the antibody to have a single CDR selected from any of the groups. Thus, the antibody of claim 1 (and dependent claims 6-13) broadly encompasses antibodies having less than six defined CDR sequences.
Each claim is a genus claim, because it encompasses a genus of antibodies possessing the recited functional characteristics; i.e., being “anti-B7H3”, which indicates the antibody binds to B7H3.
The Federal Circuit in Amgen v. Sanofi, 872 F.3d 1367 (Fed. Circ. 2017) held that a claim directed to an antibody requires written description of the antibody itself rather than being satisfied solely by a written description of the antigen to which it binds (the so-called "newly characterized antigen" test). Thus, a description of the target protein (e.g. B7H3) itself is not sufficient to provide a written description of the genus of antibodies that bind to said target. Thus, in the instant case the specification must provide a written description of the structure of the claimed antibodies.
While the general structure of an antibody is well-known in the art, the specific structure of the portion of an antibody that provides its functionality, i.e., the ability to bind to a particular antigen, is not. The antigen-binding site is formed by the association of the heavy and light chain variable regions, which each have three CDRs that provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen-binding specificity and affinity which is characteristic of the immunoglobulin. Furthermore, the set of CDRs in one antibody is independent of the set found in each other antibody, and thus knowledge of one set of CDRs does not provide any predictable information about other sets of CDRs that provide binding specificity, even with regard to the same antigen.
While the disclosure of a set of six CDRs that form an antigen-binding site capable of binding to B7H3 is sufficient to provide to describe an antibody comprising said six CDRs, it is not sufficient to provide a description of the genus of antibodies encompassed by the instant claims, which encompass a genus of antibodies having less than the full complement of defined CDRs. For example, the description of an anti-B7H3 antibody having the HCDRs of SEQ ID NO:83-85 and the LCDRs of SEQ ID NO: SEQ ID NO: 86-88 does not provide a description of other CDRs that could be substituted for one or more of SEQ ID NO: 83-85 or SEQ ID NO: 86-88 and still produce an antibody capable of binding to B7H3. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. The instant specification does not provide a description of other sequences that can complement the recited CDR sequences and form a functional antibody. The recited functional limitation (binding to B7h3) is not sufficient to define the genus because it is only an indication of what the antibody does, rather than what sequences can be used and provide said functionality. The specification fails to disclose relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention.
MPEP 2163 provides guidance for complying with the written description requirement of 35 U.S.C. 112(a) that the “specification shall contain a written description of the invention…”; this requirement is separate and distinct from the enablement requirement (Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010)). Written description for a claimed genus may be satisfied through sufficient description of a relevant number of species. This is dependent on whether one of skill in the art would recognize necessary common attributes or features possessed by the members of the genus. Generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. Written description for a claimed genus can also be satisfied when relevant identifying characteristics are disclosed. Per MPEP 2163, “[d]etermine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. For example, if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function.” However, claiming by function does not necessarily satisfy the written description requirement. “[A] generic statement such as "vertebrate insulin cDNA" or "mammalian insulin cDNA," without more, is not an adequate written description of the genus because it does not distinguish the claimed genus from others, except by function. It does not specifically define any of the genes that fall within its definition. It does not define any structural features commonly possessed by members of the genus that distinguish them from others … A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. It is only a definition of a useful result rather than a definition of what achieves that result” (Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). Also, “[w]hen a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)), and “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus” (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states “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” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of antibody variants, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and 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). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 (BPAI 1993). In Fiddes, claims directed to mammalian FGFs were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, only an anti-B7H3 monoclonal antibody or an antigen-binding fragment thereof, comprising a set of three HCDRs and three LCDRs selected from one of combinations (a)-(n) as recited in claim 1, but not the full breadth of the claims meets the written description provision of 35 U.S.C. §112(a). Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (pg 1115).
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.-Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3-5 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Per MPEP 608.01(n).III, “If the dependent claim does not comply with the requirements of 35 U.S.C. 112(d), the examiner should reject the dependent claim under 35 U.S.C. 112(d) rather than objecting to the claim” and “a dependent claim must be rejected under 35 U.S.C. 112(d) if it omits an element from the claim upon which it depends or it fails to add a limitation to the claim upon which it depends”.
Claim 3 further limits the anti-B7H3 monoclonal antibody (or antigen-binding fragment thereof) of claim 2 to one wherein the heavy and light chain variable regions are humanized. However, parent claim 2 is limited to sets of heavy and light chain variable regions that are fully defined by amino acid sequence; e.g. an antibody comprising a heavy chain variable region of SEQ ID NO: 1 and a light chain variable region of SEQ ID NO: 2. Any changes made to these sequences in order to humanize them will result in amino acid sequences that are not encompassed by the parent claim. As such, claim 3 is directed to antibodies outside the scope of parent claim 2, and thus fails to further limit claim 2.
Claim 4 depends from claim 3 and further defines the humanized sequences by reference to specific amino acid sequences, i.e., SEQ ID NO: 113/114. However, as with parent claim 3, these humanized sequences are not encompassed by the amino acid sequences recited in claim 2. As such, claim 4 is directed to antibodies outside the scope of parent claim 2, and thus fails to further limit claim 2.
Claim 5 depends from claim 4 and is included in the rejection for the same reasons.
Therefore, dependent claims 3-5 are of improper dependent form because these claims fail to further limit the subject matter of parent claim 2.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(b)
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 6, 8-10 and 12-13 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 pre-AIA the applicant regards as the invention.
Claims 6 and 8 are each directed to a “method for using” an anti-B7H3 antibody (claim 6) or conjugate of such (claim 8) “for at least one of: regulating B7H3 activity or B7H3 level, selectively killing or inhibiting a tumor through toxin conjugation, mediating antibody-dependent cytotoxicity (ADCC), blocking an effect of B7H3 in immunosuppression to enhance body immunity, promoting T lymphocyte, or improving production of a cytokine”. Claim 9 is directed to a “method for using” the conjugate “for preventing, treating and/or adjuvantly treating a tumor”. Each of these claims is directed to reciting a list of intended uses for the antibody, but without setting forth any steps of how each use is actually practiced. Claims 12 and 13 depend from claims 6 and 8 and also fail to recited any method steps. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced. See MPEP 2173.05(q), which states:
"Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986)."
MPEP 2173.05(q) further states, “It is appropriate to reject a claim that recites a use but fails to recite steps under 35 U.S.C. 101 and 35 U.S.C. 112(b) if the facts support both rejections”. As such, claims 6 are indefinite for reciting a use without any active, positive steps. See also the rejection of the claims below in the section titled "Claim Rejections - 35 USC § 101".
In claim 6 and 8, the term “promoting T lymphocyte” is unclear as to what activity or attribute of the T lymphocyte is being promoted.
In claim 10, the recitation of “a nucleic acid molecule of the anti-B7H3 monoclonal antibody” is unclear because it is not known what is meant by the nucleic acid being “of the” antibody. Generally, the relationship would be that of the nucleic acid molecule encoding the antibody; e.g., “…a nucleic acid molecule encoding the anti-B7H3 monoclonal antibody…”
Claims 12 and 13 are also indefinite with respect to the phrase, “the cytokine is IFN-γ in T lymphocyte”, which is unclear because IFN-γ is a soluble cytokine secreted by cells, and not found “in” cells.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 6, 8-9 and 12-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to nonstatutory subject matter.
Claims 6, 8-9 and 12-13 are each directed to a method of using an antibody, or conjugate thereof, but without reciting any specific method steps. These claims do not fall within at least one of the four categories of patent eligible subject matter because, per MPEP 217.05(q): ““Use” claims that do not purport to claim a process, machine, manufacture, or composition of matter fail with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)(“one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101”).”
Conclusion
Claim 2 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
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