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 .
1. Claims 1-13 are pending and being examined.
Claim Objections
2. Claim 3 is free of the art but 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.
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.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
3. Claim 11 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claim 11 recites a transformed cell comprising an expression unit containing the polynucleotide according to claim 9 and a promoter operably linked thereto.
The instant specification discloses that cells encompass eukaryotic cells, animal cells, and mammalian cells (see published specification [61]; [74]). The broadest reasonable interpretation of claim 11 is transformed mammalian cells including those found in a human. Therefore claim 11 encompasses transgenic humans.
Examiner Suggestion: Amend claim 11 to recite: An isolated transformed cell…
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, 4-7, 9-12 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. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn a method of treating or preventing an inflammatory disease, comprising administering an effective amount of a neutralizing antibody specific to human denatured CRP for treating or preventing the inflammatory disease to a subject in need thereof; wherein the neutralizing antibody binds to SEQ ID NO:2; transformed cells expressing a polynucleotide encoding the antibody; and a pharmaceutical composition comprising the antibody.
Thus, the claims identify the antibody by function only, where the function is to:
Bind and neutralize human denatured CRP, SEQ ID NO:2; and
Treat or prevent an inflammatory disease in a subject.
No antibody structure is recited. The claims are drawn to a vast genus of antibodies of unknown structure and required to function as listed above.
The instant specification discloses producing antibodies against human CRP antigen in mice, isolating hybridomas producing antibodies binding to CRP, testing neutralizing activity in ELISA, identifying seven clones (3C, 12C, 18A, 19C, 21A, and 35A) as having enhanced binding, and selecting three clones (3C, 12C, 18A) for sequencing (Examples 1-3). The instant specification discloses in Table 2 the heavy and light chain sequences of antibody 3C:
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The instant specification then tested epitope binding of antibody 3C with various peptides derived from human CRP, and determined the antibody binds to epitope SEQ ID NO:2. Antibodies 12C and 18A were tested for binding to SEQ ID NO:2 and did not bind to SEQ ID NO:2 (Example 4). Therefore, the instant specification describes a single exemplary antibody, 3C, comprising heavy and light chain CDR SEQ ID NOs:5-7 and 10-11, that binds to human CRP epitope SEQ ID NO:2.
The instant specification further demonstrates that antibody 3C successfully treats inflammation in a peritonitis and arthritis model, and demonstrates antibody 3C markedly reduced infiltration of inflammatory cells into joints, preventing destruction of articular cartilage (Examples 7 and 9).
Thus, the instant specification describes the sequences of a single mouse monoclonal anti-CRP antibody 3C that binds to and neutralizes denatured CRP epitope SEQ ID NO:2 and treats/prevents inflammation as claimed. The specification fails to disclose any other structural sequence required of any other antibody to possess the functions claimed and listed above.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative antibodies that function as claimed and listed above, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
In this case, the only factor present in the claims is a recitation of the antibody functions, as listed above. The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification discloses a single exemplary monoclonal antibody sequence that functions as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. Other than for antibody 3C comprising CDR SEQ ID NOs:5-7 and 10-12, the specification fails to provide any structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of antibody sequences for the genus of antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to perform the claimed method.
In the instant case, the specification discloses a single mouse monoclonal anti-CRP antibody that functions as claimed. Other than for antibody 3C, the instant specification does not disclose any exemplary sequence of an antibody that functions as claimed, and does not disclose the six complementarity determining regions (CDRs) or variable light chain domain (VL) + variable heavy chain domain (VH) sequences necessary for the antibody to function as claimed. The specification does not disclose the sequence structure of any other antibody that would predictably function as claimed. Applicants have not established any reasonable structure-function correlation with regards to the sequences in the variable domains or CDRs that can be altered and still maintain CRP binding function and neutralize CRP, bind SEQ ID NO:2, and treat or prevent an inflammatory disease as claimed. The instant claims attempt to claim every antibody that would achieve a desired result, i.e., bind human denatured CRP, neutralize CRP, bind SEQ ID NO:2, and treat or prevent an inflammatory disease, wherein the instant specification does not describe representative examples to support the full scope of the claims because the instant specification discloses a single mouse monoclonal anti-CRP antibody that functions as claimed. Given the well-known high level of polymorphism of antibody CDR sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of antibodies encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a single mouse monoclonal anti-CRP antibody to the structure of any and all anti-CRP antibodies required to function as broadly claimed. Therefore, one could not readily envision members of the broadly claimed genus required to practice the invention.
Although Applicants may argue that it is possible to screen for antibodies that bind human denatured CRP or epitope SEQ ID NO:2 and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘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.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. The human denatured CRP or epitope SEQ ID NO:2 antigen provides no information about the structure of an antibody that binds to it.
Given the lack of representative examples to support the full scope of the claimed antibodies used in the claimed method, and lack of reasonable structure-function correlation with regards to the unknown sequences in the variable domains or CDRs that provide the functions of binding human denatured CRP, neutralizing CRP, binding SEQ ID NO:2, and treating or preventing an inflammatory disease, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibodies that bind human denatured CRP, neutralize CRP, bind SEQ ID NO:2, and treat or prevent an inflammatory disease that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Examiner Suggestion: Amend the limitations of claim 3 into claim 1. Amend the limitations of claim 8 into claim 7. Amend the limitations of claim 13 into claim 12.
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.
5. Claims 7-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/448,519 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application claims recite an antibody the binds to denatured CRP, wherein the antibody comprises heavy chain variable region sequence from SEQ ID NO:4 and a light chain variable region sequence from SEQ ID NO:9. SEQ ID NO4 comprises 100% of instant CDR SEQ ID NOs:5, 6, and 7; and SEQ ID NO:9 comprises 100% of instant SEQ ID NOs:10, 11, and 12 (see sequence alignments below), thereby rendering the instantly claimed antibody, its encoding polynucleotide, and its compositions containing them obvious. The copending application claims:
1. A method for testing adult Still's disease, comprising the following (1) and (2):
(1) measuring a denatured CRP concentration in a blood sample collected from a subject; and
(2) comparing the measured denatured CRP concentration and/or an index value based on the denatured CRP concentration with a reference value.
11. The method according to claim 1, wherein the denatured CRP concentration is measured using a denatured CRP-specific antibody.
12. The method according to claim 11, wherein the denatured CRP concentration is measured using the denatured CRP-specific antibody selected from the group consisting of the following (1) to (3), or a combination thereof:
(1) an antibody comprising the following (1a) and (1b):
(1a) an antibody heavy chain containing a variable region comprising an amino acid sequence having an identity of 90% or more to the amino acid sequence consisting of the amino acid residues at positions 20 to 133 in the amino acid sequence of SEQ ID NO: 4.
13. A denatured CRP-specific antibody selected from the group consisting of the following (1) to (3):
(1) an antibody comprising the following (1a) and (1b):
(1a) an antibody heavy chain containing a variable region comprising an amino acid sequence having an identity of 90% or more to the amino acid sequence consisting of the amino acid residues at positions 20 to 133 in the amino acid sequence of SEQ ID NO: 4, and
(1b) an antibody light chain containing a variable region comprising an amino acid sequence having an identity of 90% or more to the amino acid sequence consisting of the amino acid residues at positions 20 to 131 in the amino acid sequence of SEQ ID NO: 9.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Instant SEQ ID NOs:5+6+7 aligned with Application 18/448,519 SEQ ID NO:4:
RESULT 7
US-18-448-519-4
Sequence 4, US/18448519
Publication No. US20230384326A1
GENERAL INFORMATION
APPLICANT: CANON MEDICAL SYSTEMS CORPORATION (en)
TITLE OF INVENTION: TEST METHOD AND TEST KIT FOR ADULT STILL'S DISEASE (en)
FILE REFERENCE: 98G81000972WOA
CURRENT APPLICATION NUMBER: US/18/448,519
CURRENT FILING DATE: 2023-08-11
NUMBER OF SEQ ID NOS: 79
SEQ ID NO 4
LENGTH: 469
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..469
QUALIFIERS: note = Amino acid sequence of the heavy chain of the
antibody 3C
FEATURE:
NAME/KEY: source
LOCATION: 1..469
QUALIFIERS: mol_type = protein
organism = Synthetic Construct
Query Match 84.6%; Score 135.4; Length 469;
Best Local Similarity 37.0%;
Matches 27; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DYEMH--------------AIHPGRGGTAYNQKFKG------------------------ 22
||||| |||||||||||||||||
Db 50 DYEMHWVKQTPVHGLEWIGAIHPGRGGTAYNQKFKGKATLTADKSSSTAYMELSSLTSED 109
Qy 23 --------YHGGY 27
|||||
Db 110 SGVYYCTSYHGGY 122
Instant SEQ ID NOs:10+11+12 aligned with Application 18/448,519 SEQ ID NO:9:
RESULT 1
US-18-448-519-9
Sequence 9, US/18448519
Publication No. US20230384326A1
GENERAL INFORMATION
APPLICANT: CANON MEDICAL SYSTEMS CORPORATION (en)
TITLE OF INVENTION: TEST METHOD AND TEST KIT FOR ADULT STILL'S DISEASE (en)
FILE REFERENCE: 98G81000972WOA
CURRENT APPLICATION NUMBER: US/18/448,519
CURRENT FILING DATE: 2023-08-11
NUMBER OF SEQ ID NOS: 79
SEQ ID NO 9
LENGTH: 238
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..238
QUALIFIERS: note = Amino acid sequence of the light chain of the
antibody 3C
FEATURE:
NAME/KEY: source
LOCATION: 1..238
QUALIFIERS: mol_type = protein
organism = Synthetic Construct
Query Match 85.2%; Score 142.3; Length 238;
Best Local Similarity 40.5%;
Matches 32; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RSSQSLVHSNENTYLL---------------KVSNRFS---------------------- 23
|||||||||||||||| |||||||
Db 43 RSSQSLVHSNENTYLLWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRV102
Qy 24 ----------SQTTHVPWT 32
|||||||||
Db 103 EAEDLGVYFCSQTTHVPWT 121
6. Conclusion: Claim 3 is objected to. Claims 1, 2, 4-13 are rejected.
The closest prior art made of record but not relied upon is US Patent 9,841,430, Kiefer, issued 2017 (IDS). Kiefer teaches making monoclonal antibodies reactive with human CRP protein SEQ ID NO:2 (206 amino acids long, see column 9), wherein SEQ ID NO:2 comprises the epitope EILFEVPEVT (instant SEQ ID NO:2) at amino acid residues 81-90. Kiefer teaches making antibodies to intact human CRP or to modified epitopes thereof, and teaches utilizing the antibodies to detect CRP indicative of inflammatory diseases. Kiefer does not teach or suggest antibodies bind to instant epitope SEQ ID NO:2 specifically, and does not teach the antibodies have neutralizing or therapeutic function.
7. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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/Laura B Goddard/Primary Examiner, Art Unit 1642