DETAILED ACTION
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 .
Status of Application, Amendments and/or Claims
1. Claims 1-10 are pending and under examination in the current application.
Information Disclosure Statement
2. The information disclosure statements (IDSs) filed 05/17/2021, 05/18/2021, 05/11/2022, 11/08/2022, and 06/20/2023 have been considered and the references therein are of record.
Claim Objections
3. Claim 1 is objected to because of the following informalities: the claim recites an acronym that is not spelled out in its first use in the claims (i.e., RGMa). It would be remedial to amend the claim language in claim 1 such that the acronym is clearly defined. Appropriate correction is required.
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.
4. Claims 1-10 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.
Claim 1 is broadly drawn to a repulsive guidance molecule (RGMa)-binding protein, which competes with the anti-RGMa antibody according to claim 1 for binding to RGMa. Dependent claim 5 is drawn to a method of producing the RGMa-binding protein, claims 6-10 are directed to a pharmaceutical composition comprising the RGMa-binding protein, and claims 2-4 are drawn to a nucleic acid molecule encoding for the RGMa-binding protein, a vector comprising the nucleic acid molecule, and a host cell containing the vector, respectively. The instant specification defines “competing” at [0029] as “measured by the surface plasmon resonance (SPR) described herein, the binding between the anti-RGMa antibody of the present invention and RGMa is decreased with a significant difference due to the presence of said anti-RGMa antibody or an antigen-binding fragment thereof.” Thus, claim 1 and dependent claims thereof encompasses a genus of binding proteins defined entirely by their function in terms of their competitive binding to RGMa but with no defined structure.
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, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The factors to be considered when analyzing claims for compliance with the written description requirement include: actual reduction to practice; disclosure of drawings or structural chemical formulas; sufficient relevant identifying characteristics (e.g., disclosure of complete or partial structure, physical and/or chemical properties, structure/function correlation); method of making the claimed invention; level of skill and knowledge in the art; and predictability in the art. See MPEP §2163.
With respect to antibodies, the Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
The recitation of binding-protein that competes with the anti-RGMa antibody of claim 1 (which is defined in terms of its six CDRs) represents a functional characteristic. While generically the structure of a protein may be known, the structure of the presently claimed binding protein can vary substantially within the above given claimed recitations, as can the structure of the nucleic acid molecule encoding for the undefined RGMa-binding protein. Thus, the genus is highly variant because a significant number of structural differences between genus members is permitted.
The instant specification discloses the production of two monoclonal antibodies, B5.116A3 and B5.70E4 (also called 116A3 and 70E4, respectively), which were raised against the C-terminal domain of RGMa. The CDR sequences of claim 1 are those of the 116A3 and 70E4 antibodies, respectively. The specification also indicates that the 116A3 mAb binds to peptides derived from residues 298-311, 322-335 and 367-377 of RGMa, whereas the 70E4 mAb bound to peptides derived from residues 298-311, 322-335 and 349-359 of human RGMa. Therefore, at best the specification discloses two species of antibodies that fall within the presently claimed genus of anti-RGMa binding proteins.
However, the specification does not disclose structural features shared by members of the genus of binding proteins. Nor does the specification provide a correlation between the structure of binding proteins and the ability to bind a particular epitope of RGMa in order to compete with binding for the epitope with, for instance, the 116A3 or 70E4 antibodies. Along these lines, there is no disclosure of nucleic acid molecules that encoding for such RGMa-binding proteins. Accordingly, there is insufficient evidence in the specification that applicant was in possession of the broad genus of binding proteins as claimed that would be capable of competing with binding to RGMa against antibodies comprising the CDRs of the 116A3 or 70E4 antibodies.
Apart from the specific 116A3 and 70E4 monoclonal antibodies and antigen-binding fragments thereof, the instant application is lacking sufficient guidance on the structural attributes of proteins, or their encoding polynucleotides, that correlate to the functional requirements of the claimed invention. Regardless, the relevant art recognizes that diversity of antibodies binding to any particular target antigen or epitope is extremely broad, and therefore there is no way to reasonably predict the structure of the antigen-binding region of an antibody based upon the structure of an antigen or epitope alone (see, for example, Lloyd et al. Protein Eng. Design & Select, 2009, 22(3):159-168; and Edwards et al. J. Mol. Biol. 2003, 334:103-118; both listed on 05/17/2021 IDS). Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus nor guidance as to which of the myriad of molecules encompassed by the claimed binding proteins would meet the limitations of the claims.
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. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014, Appeal No. 13-1338 at page 26). Therefore, the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112(a).
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.
5. Claims 1-10 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.
The recitation in claim 1 of “An RMGa-binding protein, which competes with an anti-RGMa antibody, wherein the anti-RGMa antibody has the amino acid sequence of each of the light chain complementary determining region 1 (LCDR1)….and the heavy chain complementary determining region 3 (HCDR3) comprises the following: LCDR1: RASQDISSYLN (SEQ ID NO: 30)…” renders the claim unclear because it is unclear whether the “comprises” refers to the the RGMa-binding protein or the anti-RGMa antibody. The metes and bounds of the claim therefore cannot be readily determined.
Dependent claims 2-10 are included in this rejection as they contain all of the limitations of independent claim 1 yet nothing in addition that would aid in clarifying the matter.
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.
6. Claim(s) 1 and 6-10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hata et al. (J. Cell Biol. 2006, 173(1):47-58; listed on 05/17/2021 IDS).
Claim interpretation: For the purpose of applying art, the “comprises” limitation in claim 1 (as discussed in section 5 above) will be interpreted as referring to the anti-RGMa antibody.
Hata et al. teach the production of an anti-RGMa antibody that was raised against a C-terminal peptide fragment of RGMa, which is residues 309-322 of RGMa (see “Anti-rat RGMa antibody production” at p. 56). The instant specification indicates that the antibodies encompassed by present claim 1 bind to epitopes that include residues 298-311 and 322-335 of RGMa. Given the substantial overlap of epitopes, the antibody of Hata would be expected to compete with an antibody encompassed by claim 1 (e.g., the 116A3 or 70E4 mAbs) for binding to RGMa, and thus meets the limitation of present claim 1.
Regarding claim 6, Hata teaches the intrathecal administration of the anti-RGMa antibody to spinal cord-injured rats (see “Surgical procedure” at p. 56), which implicitly provides for a pharmaceutical composition comprising the anti-RGMa antibody.
And regarding claims 7-10, which recite a pharmaceutical composition for use in treating or reducing the relapse of neurological or immunological diseases, it is noted that the recitation of “for use in…” is an intended use of the claimed composition. Intended use recitations and other types of functional language cannot be entirely disregarded. However, in apparatus, article, and composition claims, intended use must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In a claim drawn to a process of making, the intended use must result in a manipulative difference as compared to the prior art. In re Casey, 370 F.2d 576, 152 USPQ 235 (CCPA 1967); In re Otto, 312 F.2d 937, 938, 136 USPQ 458, 459 (CCPA 1963).
In the instant case, the prior art antibody is capable of performing the intended use, and thus completely anticipates the claims. Moreover, Hata demonstrates that the anti-RGMa antibody improved recovery of the spinal cord-injured rats, and spinal cord injury and neurotrauma are listed in the present claims. Therefore, the pharmaceutical composition comprising an anti-RGMa antibody taught by Hata anticipates the invention of present claims 1 and 6-10.
Double Patenting
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.
7. Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,008,388. Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims encompass an RGMa-binding molecule, pharmaceutical composition comprising same, nucleic acid molecules encoding for the binding molecule, recombinant vector comprising the nucleic acid, host cell comprising the vector, and method of recombinantly producing the anti-RGMa molecule. Importantly, the patented ‘388 claims are directed to an anti-RGMa antibody, which antibody comprises one of two different sets of six CDR sequences; these light chain and heavy chain CDR sequences of the patented claims are identical to those recited in present claim 1 (i.e., the anti-RGMa antibody against which the presently claimed RGMa-binding protein competes). Accordingly, the antibodies of the patented claims (which CDRs are those of 116A3 and 70E4 mAbs, respectively) are capable of competing with each other (i.e., 116A3 vs 70E4) or with themselves (i.e., 116A3 vs 116A3; 70E4 vs 70E4) for binding to RGMa, and thus are species that anticipate the genus of anti-RGMa binding proteins of the instant claims.
Additionally, patented claims 14-17 are directed to therapeutic methods of treating or reducing relapse of a neurological or immunological disease in a subject, which anticipate the intended use limitations of the pharmaceutical composition of present claims 7-10.
8. Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,287,346. Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims encompass an RGMa binding protein, pharmaceutical compositions thereof, nucleic acid molecules encoding for the antibody, vectors and host cells comprising the nucleic acid molecule and/or vector, and method of recombinantly producing the antibody. Importantly, the patented ‘346 claims are directed to an anti-RGMa antibody, which antibody comprises one of two different sets of six CDR sequences; these light chain and heavy chain CDR sequences of the patented claims are identical to those recited in present claim 1 (i.e., the anti-RGMa antibody against which the presently claimed RGMa-binding protein competes). Accordingly, the antibodies of the patented claims (which CDRs are those of 116A3 and 70E4 mAbs, respectively) are capable of competing with each other (i.e., 116A3 vs 70E4) or with themselves (i.e., 116A3 vs 116A3; 70E4 vs 70E4) for binding to RGMa, and thus are species that anticipate the genus of anti-RGMa binding proteins of the instant claims.
Conclusion
9. No claims are allowed.
Advisory Information
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/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675