DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I, claims 47(a) and (c); 48-50 partially, and new claim 60, i.e., single domain antibody which binds to Clostridium difficile toxin B comprising a complementary- determining region 1 (CDR1) consisting of SEQ ID NO: 1; and a complementary-determining region 2 (CDR2) consisting of SEQ ID NO: 2; and a complementary-determining region 3 (CDR3) consisting of SEQ ID NO: 3, in the reply filed on 5/26/26 is acknowledged.
Upon further consideration, part (b) of claim 1 and claim 51 will also be examined as they are also drawn to the CD3A antibody.
Claims 52-59 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Sequence Compliance for Figure
It is noted that Figure 3 of the instant specification recites a nucleotide/amino acid sequences which are encompassed by the definitions for nucleotide sequences as set forth in 37 C.F.R. 1.821(a)(1) and (a)(2). The M.P.E.P., Section 2422.02, 37 CFR 1.821(b) requires exclusive conformance, with regard to the manner in which the nucleotide/amino acid sequences are presented and described, with the sequence rules for all applications that include nucleotide sequences that fall within the definitions. When a sequence is presented in a drawing, regardless of the format or the manner of the presentation of that sequence in the drawing, the sequence must still be included in the Sequence Listing and the sequence identifier (“SEQ ID NO:X”) must be used, either in the drawing or in the Brief Description of the Drawings.
APPLICANT MUST COMPLY WITH THE SEQUENCE RULES WITHIN THE SAME TIME PERIOD AS IS GIVEN FOR RESPONSE TO THIS ACTION, 37 C.F.R. 1.821-25. Failure to comply with these requirements will result in ABANDONMENT of the application under 37 C.F.R. 1.821(g). Extensions of time may be obtained by filing a petition accompanied by the extension fee under the provisions of 37 C.F.R. 1.136. In no case may an applicant extend the period for response beyond the six-month statutory period.
Claim Rejections - 35 USC § 112-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 47 (part b)-50 and 60 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 47 part (b) and claim 60 recite:
A single domain antibody which binds to Clostridium difficile toxin B, wherein the single domain antibody is selected from the group consisting of:
b) a single domain antibody comprising or consisting of an amino acid sequence as set forth in SEQ ID NO: 22, or an amino acid sequence having at least 90% sequence identity thereto, wherein any sequence variance relative to SEQ ID NO: 22 is outside the complementarity-determining regions (CDRs)
A single domain antibody which binds to Clostridium difficile toxin B, wherein the single domain antibody comprises an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 22, wherein the amino acid sequence comprises: i. a complementarity-determining region 1 (CDR1) consisting of SEQ ID NO: 1; ii. a complementarity-determining region 2 (CDR2) consisting of SEQ ID NO: 2; and iii. a complementarity - determining region 3 (CDR3) consisting of SEQ ID NO: 3; and wherein any amino acid sequence variation relative to SEQ ID NO: 22 is outside CRD1, CDR2 and CDR3.
To fulfill the written description requirements set forth under 35 USC § 112, first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession the claimed invention. Applicants have not described the genus of claimed antibodies such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the claimed invention at the time the application was filed.
The purpose of the "written description" requirement is broader than tomerely explain how to "make and use"; the applicant must convey with reasonableclarity to those skilled in the art that, as of the filing date sought, he or she was inpossession of the invention. The invention is, for purposes of the "writtendescription" inquiry, whatever is now claimed. See Vas-Cath, Inc. v. Mahurkar,935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).Furthermore, the written description provision of 35 USC § 112 is severable fromits enablement provision; and adequate written description requires more than amere statement that it is part of the invention and reference to a potential methodfor isolating it. The nucleic acid itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, paragraph 1, "'Written Description" Requirement (66 FR 1099-1111, January 5,2001) state, "[p]ossession may be shown in a variety of ways including description of an actualreduction to practice, or by showing the invention was 'ready for patenting' such asby disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention" (Id. at 1104). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. The Guidelines further state, "[f]or inventions in an unpredictable art, adequatewritten description of a genus which embraces widely variant species cannot beachieved by disclosing only one species within the genus'" (Id. at 1106);accordingly, it follows that an adequate written description of a genus cannot beachieved in the absence of a disclosure of at least one species within the genus.
As evidenced by Greenspan et al (Nature Biotechnology 7: 936-937, 1999), defining epitopes is not as easy as it seems. Greenspan et al recommends defining anepitope by the structural characterization of the molecular interface between theantigen and the antibody is necessary to define an "epitope" (page 937, column 2).According to Greenspan et al, an epitope will include residues that make contactswith a ligand, here the antibody, but are energetically neutral, or even destabilizingto binding. Furthermore, an epitope will not include any residue not contacted by the antibody, even though substitution of such a residue might profoundly affectbinding. Chothia et al (THE EMBO JOURNAL, 1986, 5/4:823-26) also teach thatthere is a limit to how much substitution can be tolerated before the originaltertiary structure is lost. Therefore, absent a detailed and particular description of arepresentative number, or at least a substantial number of the members of thegenus of fragments or variants of the eleven peptides, the skilled artisan could notimmediately recognize that Applicants were in possession of the claimed genus ofpeptides at the time of filing.
The scope of the claim includes numerous structural variants, and the genus is highly variant because a significant number of structural differences between genus members is permitted. The specification does not describe any members of the claimed genus by complete structure. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the claimed genus. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
There are no drawings or structural formulas disclosed of any of thesevariant antibodies. There is no teaching in the specification of other CD3A antibodies with different sequences. Although the disclosure of SEQ ID NO: 22 combined with the knowledge in the art, may put one in possession of peptides that are at least 90% identical to SEQ ID NO: 22, the level of skill and knowledge in the art is such that one of ordinary skill would not be able to identify without further testing which are single domain antibodies with the same binding ability.
Based on the lack of knowledge and predictability in the art, those of ordinaryskill in the art would not conclude that the applicant was in possession of theclaimed genus of antibodies.
Allowable Subject Matter
Claim 51 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.
Status of Claims:
No claims are presently allowed.
“A single domain antibody comprising CDR1 comprising or consisting of SEQ ID NO: 1; and A single domain antibody comprising CDR2 comprising or consisting of SEQ ID NO: 2; and A single domain antibody comprising CDR3 comprising or consisting of SEQ ID NO: 3; and humanized version thereof;
And
A single domain antibody comprising or consisting of SEQ ID NO: 22” are free of the prior art.
Correspondence regarding this application should be directed to Group Art Unit 1645. Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center located in Remsen. The faxing of such papers must conform with the notice published in the Official Gazette, 1096 OG 30 (November 15,1989). The Group 1645 Fax number is 571-273-8300 which is able to receive transmissions 24 hours/day, 7 days/week.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer E. Graser whose telephone number is (571) 272-0858. The examiner can normally be reached on Monday-Friday from 8:00 AM-4 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Thomas Visone, can be reached at (571) 270-0684.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-0500.
/JENNIFER E GRASER/ Primary Examiner, Art Unit 1645 7/7/26
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