DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s election without traverse of Group II (drawn to a method for treating a disorder) in the Response filed on June 18, 2026 is acknowledged.
Upon further consideration, the previous Requirement for Restriction/Election mailed on February 20, 2026 has been withdrawn.
In view of the withdrawal of the restriction requirement, applicants are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 1 and 2 are pending and currently under consideration.
3. Claim 2 is objected to for following informalities:
Claim 2 recites SEQ ID NO:11 as CDRH2. However, it is apparent that SEQ ID NO:11 is the amino acid sequence of CDRH3 (see claim 1). Appropriate correction is required.
4. 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.
5. Claims 1 and 2 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.
Claim 1 is drawn to an anti-FcRn antibody comprising a CDR1 L1 having no more than two amino acid substitutions relative to SEQ ID NO:1, a CDR L2 having no more than one amino acid substitution relative to SEQ ID NO:2, a CDR L3 having no more than one amino acid substitution relative to SEQ ID NO:3, a CDR H1 having no more than one amino acid substitution relative to SEQ ID NO:5 or SEQ ID NO:6, a CDR H2 having no more than two amino acid substitutions relative to SEQ ID NOs: 7, 8, 9, or 10, a CDR H3 having no more than one amino acid substitution relative to SEQ ID NO:11.
Claim 2 is drawn to a method for treating a disorder by administering the anti-human FcRn antibody as recited in claim 1.
The specification discloses five anti-human FcRn antibodies with specific amino acid sequences for all six CDRs (e.g. see Table 1 in page 16 of the specification as-filed). These antibodies have the same CDRs L1-3 and CDR H3 amino acid sequences. They also share the same light chain amino acid sequence of SEQ ID NO:19 (e.g. see Table 2 in page 17 of the specification as-filed).
However, there is insufficient written description in the specification as-filed of the claimed anti-huma FcRn antibodies comprising no more than two or no more than one amino acid substitutions in the CDRs as recited in the instant claims.
The instant application has not provided a sufficient description showing possession of the necessary 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 genus of the anti-FcRn antibodies broadly encompassed by the claimed invention.
In Abbvie Deutschland Gmbh & Co KG, Abbvie Bioresearch Center, Inc.,and Abbvie Biotechnolo~, Ltd., v. Janssen Biotech In. And Centocor Biologics,LLC, Case No. 2013-1338 and 2013- 1346, C.A.Fed. ("Abbvie"), the Federal Circuit reiterates the inherent unpredictability of protein engineering in Abbvie. For example, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology."); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen- Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). However, the record here does not indicate such an established correlation. Instead, AbbVie used a trial and error approach to modify individual amino acids in order to improve the IL-12 binding affinity.”
The claims recite a genus of anti-human FcRn antibodies comprising the amino acid sequences for the six CDRs comprising no more than two or no more than amino acid substitutions without setting forth which one or two amino acids within the CDRs can be substituted to any particular residues for an antibody that would maintain binding to human FcRn. The genus of the anti-human FcRn antibodies is therefore very large. Applicant has disclosed five specific anti-human FcRn antibodies that share sequence homologies. Thus, applicant has disclosed only limited species of the antibodies. The claimed antibodies lack a common structure essential for their function of binding human FcRn.
Antibody modifications can be unpredictable. For example, Cannon et al. (PLOS Computational Biology May 1, 2019 pages 1-22) teach that strategies for antibody affinity maturation such as a structure-based rationale or a mini-library approach hinge primarily on two factors: a high-quality co-crystal structure and an algorithm to calculate the energy change that occurs upon mutation (e.g. see 3rd paragraph under Introduction in page 2). Cannon et al. further teach building a homology model of an Fv fragment of an antibody and using NMR structure of the antigen for protein-protein docketing for making antibody mutants, however, this process requires full length of VH and VL (in the form of Fv) (e.g. see Results in page 3). Cannon et al. teach that five positions when replaced with alanine resulted in complete loss of antigen binding (e.g. see Figure 5 and tope paragraph under Table 3 in page 8). Cannon et al. only identified two affinity-improved mutations (e.g. see Top paragraph in page 14).
It does not appear based upon the limited disclosure of four antibodies alone that applicant was in passion of the necessary common attributes or features of the elements possessed by the members of the genus in view of the limited number of species disclosed and the extensive variation permitted within the genus of anti-human FcRn antibodies.
“Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Regents of the University of California v. Eli Lilly and Co. 43 USPQ2d 1398 (Fed. Cir. 1997).
In the absence of disclosure of relevant, identifying characteristics of the anti-human FcRn antibodies including defined structure of six CDRs including specific mutations in specific positions to specific amino acid residues, there is insufficient written disclosure under 35 U.S.C. 112, first paragraph. Logically, if applicant was not in possession of the antibody which is being administered, applicant also was not in possession of methods of administering such reagents at the time the instant application was filed.
6. Claims 1 and 2 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 1 is drawn to an anti-FcRn antibody comprising a CDR1 L1 having no more than two amino acid substitutions relative to SEQ ID NO:1, a CDR L2 having no more than one amino acid substitution relative to SEQ ID NO:2, a CDR L3 having no more than one amino acid substitution relative to SEQ ID NO:3, a CDR H1 having no more than one amino acid substitution relative to SEQ ID NO:5 or SEQ ID NO:6, a CDR H2 having no more than two amino acid substitutions relative to SEQ ID NOs: 7, 8, 9, or 10, a CDR H3 having no more than one amino acid substitution relative to SEQ ID NO:11.
Claim 2 is drawn to a method for treating a disorder by administering the anti-human FcRn antibody as recited in claim 1.
The specification discloses five anti-human FcRn antibodies with specific amino acid sequences for all six CDRs (e.g. see Table 1 in page 16 of the specification as-filed). These antibodies have the same CDRs L1-3 and CDR H3 amino acid sequences. They also share the same light chain amino acid sequence of SEQ ID NO:19 (e.g. see Table 2 in page 17 of the specification as-filed).
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Antibody modifications can be unpredictable. For example, Cannon et al. (PLOS Computational Biology May 1, 2019 pages 1-22) teach that strategies for antibody affinity maturation such as a structure-based rationale or a mini-library approach hinge primarily on two factors: a high-quality co-crystal structure and an algorithm to calculate the energy change that occurs upon mutation (e.g. see 3rd paragraph under Introduction in page 2). Cannon et al. further teach building a homology model of an Fv fragment of an antibody and using NMR structure of the antigen for protein-protein docketing for making antibody mutants, however, this process requires full length of VH and VL (in the form of Fv) (e.g. see Results in page 3). Cannon et al. teach that five positions when replaced with alanine resulted in complete loss of antigen binding (e.g. see Figure 5 and tope paragraph under Table 3 in page 8). Cannon et al. only identified two affinity-improved mutations (e.g. see Top paragraph in page 14).
The claimed anti-human FcRn antibodies encompass mutations (no more than one or no more than two) in all of the six CDR regions without setting which positions within the CDRs can be mutated with the particular amino acid residues so the antigen binding specificity can be maintained. The claims do not recite sufficient structural elements or specificity for the anti-human FcRn antibody encompassed by the claimed method. The specification does not provide sufficient guidance and direction to identify and to enable no more than one or no more than two amino acid substitutions within the CDRs for an anti-FcRn antibody to have the same function of antigen binding and to be used in a method of treating an unidentified disorder.
Regarding the method of treating a disorder by administering the antibody, note that the specification discloses the anti-human FcRn antibody N027 can decrease the IgG level and the percentage of unoccupied FcRn in mice and cynomolgus monkeys (e.g. see Examples 6 and 7 in pages 32-33 of the specification as-filed). The specification further discloses that the circulating platelet levels were decreased by 72 hours after administering anti-human FcRn antibody N027 to mouse chronic idiopathic thrombocytopenia purpura (ITP) (e.g. see Example 10 in page 33 of the specification as-filed).
There is insufficient objective evidence that data provided in the instant specification in experimental mouse ITP models can be extrapolated to enable a broad method of treating any or all disorder by administering the anti-human FcRn antibody. There is insufficient objective evidence that the skilled artisan would be able to predict which amino acid residues within the six CDRs can be substituted so that the antibody would maintain the function of antigen binding and to administer such antibody to treat an unidentified disorder.
The scope of the required enablement varies inversely with the degree of predictability involved and in cases involving unpredictable factors such as physiological activity more may be required. See MPEP 2164.03 and 2164.02.
In view of the lack of predictability of the art to which the invention pertains, making and use the claimed anti-human FcRn antibody and method of treating a disorder by administering the antibody would be unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue.
7. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
8. Claims 1 and 2 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-26 of US 11,732,047 (the ‘047 Patent, reference on IDS, the claims are drawn to a method for treating a disorder such as pemphigus vulgaris by administering an anti-FcRn antibody), and
claims 1-18 of US 10,676,526 (the ‘526 Patent, reference on IDS, claims are drawn to an anti-FcRn antibody).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the claims in the two US Patents are drawn to the same or nearly the same anti-FcRn antibody comprising the same or nearly the same CDR sequences and a method of treating a disease by administering the antibody. As such, the species of the anti-FcRn antibody having specific CDR sequences and the method of treating a specific disease such as pemphigus vulgaris in the claims of the ‘526 Patent and the ‘074 Patent would anticipate the instant genus of anti-FcRn antibody comprising the six CDRs comprising no more than one or no more than two amino acid substitutions and a method of treating a disorder. Therefore, the claims in the two US Patents would anticipate the instant invention.
9. No claim is allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHUN W DAHLE/Primary Examiner, Art Unit 1641
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