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 Claims
Claims 13-24 and 30-33 are cancelled. Claims 25-29 and 34-36 are withdrawn. Claims -----1-12 are currently under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The claims have an earliest effective filing date of 12/31/2019, corresponding to application 62/955,569.
Election/Restrictions
Claims 25-29 and 34-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/25/2025.
Applicant elected the following antibody species for examination:
Species 1: A CD160 binding molecule comprising CDRL1: SEQ ID NO: 2; CDRL2: SEQ ID NO: 3; CDRL3: SEQ ID NO: 4; CDRH1: SEQ ID NO: 6; CDRH2: SEQ ID NO: 7; CDRH3: SEQ ID NO: 8.
Species 2: A CD160 binding molecule comprising CDRL1: SEQ ID NO: 10; CDRL2: SEQ ID NO: 3; CDRL3: SEQ ID NO: 4; CDRH1: SEQ ID NO: 6; CDRH2: SEQ ID NO: 7; CDRH3: SEQ ID NO: 8.
Species 3: A CD160 binding molecule comprising CDRL1: SEQ ID NO: 2; CDRL2: SEQ ID NO: 11; CDRL3: SEQ ID NO: 4; CDRH1: SEQ ID NO: 6; CDRH2: SEQ ID NO: 7; CDRH3: SEQ ID NO: 8.
Species 4: A CD160 binding molecule comprising CDRL1: SEQ ID NO: 2; CDRL2: SEQ ID NO: 3; CDRL3: SEQ ID NO: 12; CDRH1: SEQ ID NO: 6; CDRH2: SEQ ID NO: 7; CDRH3: SEQ ID NO: 8.
Species 5: A CD160 binding molecule comprising CDRL1: SEQ ID NO: 2; CDRL2: SEQ ID NO: 3; CDRL3: SEQ ID NO: 4; CDRH1: SEQ ID NO: 14; CDRH2: SEQ ID NO: 7; CDRH3: SEQ ID NO: 8.
Note on Prior Art
The elected species 1-5 with the disclosed CDRs above are free of the prior art.
Claim Objections
Claim 1 is objected to for reciting “Table 1A”, “Table 3A”, “Table 1B”, “Table 3B”, “Table 1C”, “Table 3C”, “Table 2A”, “Table 4A”, “Table 2B”, “Table 4B”, “Table 2C”, “Table 4C” in the claim. MPEP 2173.05(s) states:
“Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table ‘is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.’ Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
In the instant case the binding agent numbers of “Table 1A”, “Table 3A”, “Table 1B”, “Table 3B”, “Table 1C”, “Table 3C”, “Table 2A”, “Table 4A”, “Table 2B”, “Table 4B”, “Table 2C”, and “Table 4C” could easily be incorporated into the claims to define the invention. Appropriate correction is required.
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 1-12 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.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claim 1 is drawn to a binding domain, e.g. an antibody that binds CD160, wherein the binding domain comprises:
a CDRL1 amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:10, SEQ ID NO:2 with one or more substitutions from Table IA and/or with one or more conservative amino acid changes, and SEQ ID NO: 10 with one or more substitutions from Table 3A and/or one or more conservative amino acid changes;
ii) a CDRL2 amino acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO: 11, SEQ ID NO:3 with one or more substitutions from Table 1B and/or with one or more conservative amino acid changes, and SEQ ID NO: 11 with one or more substitutions from Table 3B and/or one or more conservative amino acid changes; and
iii) a CDRL3 amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:12, SEQ ID NO:4 with one or more substitutions from Table 1C and/or with one or more conservative amino acid changes, and SEQ ID NO: 12 with one or more substitutions from Table 3C and/or one or more conservative amino acid changes; and
b) a heavy chain variable region, wherein said heavy chain variable region comprises:
i) a CDRH1 amino acid sequence selected from the group consisting of SEQ ID NO:6, SEQ ID NO:14, SEQ ID NO:6 with one or more substitutions from Table 2A and/or with one or more conservative amino acid changes, and SEQ ID NO: 14 with one or more substitutions from Table 4A and/or with one or more conservative amino acid changes;
ii) a CDRH2 amino acid sequence selected from the group consisting of SEQ ID NO:7, SEQ ID NO:15, SEQ ID NO:7 with one or more substitutions from Table 2B and/or with one or more conservative amino acid changes, and SEQ ID NO: 15 with one or more substitutions from Table 4B and/or with one or more conservative amino acid changes; and
iii) a CDRH3 amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:16, SEQ ID NO:8 with one or more substitutions from Table 2C and/or with one or more conservative amino acid changes, and SEQ ID NO: 16 with one or more substitutions from Table 4C and/or with one or more conservative amino acid changes.
which does not comprise a light chain variable region L-CDR1, L-CDR2 and L-CDR3. The claims encompass a large number of anti-CD160 antibodies having diverse heavy and light chain CDR amino acid sequences. Following a review of the specification, it appears that Applicant has disclosed multiple anti-CD160 binding domains, see, for example, the elected anti-CD160 binding domain species. However in view of this disclosure, Applicant is claiming a broad genus of molecules that would be expected to encompass multiple anti-CD160 binding domains having diverse heavy and light chain CDR sequences. Even though Applicant has disclosed multiple species within said genus, the specification does not provide adequate written description for the entire claimed genus, because one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed, specifically, which light and heavy chain CDR sequences (and combinations of said CDR sequences) give rise to antibody molecules capable of binding CD160. As detailed below Applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such Applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by 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 claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, Applicant has disclosed multiple species within the genus claimed. However given the substantial antibody structure variation within the genus, the disclosure of said species comprised within the claimed genus is not sufficiently representative of the entire genus.
Furthermore Applicant has not disclosed relevant, identifying characteristics of CDR region amino acid sequences (or combinations thereof) that confer upon an antibody the ability to bind CD160, because the instant specification does not provide structural antibody features that correlate with a functional ability to bind CD160. To elaborate on why the claimed antibodies lack adequate written description, Mariuzza (Annu. Rev. Biophys. Biophys. Chem., 16: 139-159, 1987) reviews the structural basis of antigen-antibody recognition and teach that naturally occurring conventional antibodies comprise two polypeptides, the so-called light and heavy chains. The antigen-combining site of an antibody is a three-dimensional structure that fully comprises six CDRs, three each from the light and heavy chains. The amino acid sequences of the CDRs are hypervariable, as the amino acid residues contained within the CDRs determine much of the antibody’s antigen-binding specificity. In view of Mariuzza, it is apparent that antibodies having less than all six CDRs that form the antigen binding site of a conventional antibody in their proper context of heavy and light chain variable domains do not describe the particularly identifying structural feature of the antibody that correlates with the antibody’s ability to bind antigen. Absent a description of the at least minimal structural features correlating with a functional ability to bind CD160 which are shared by members of a genus commonly sharing this function, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish which heavy and light chain CDR amino acid sequences (or combinations thereof) may be combined such that the resultant heavy and light chain variable regions comprise six CDRs that confer the ability to bind CD160.
Furthermore while the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. For example in a series of experiments involving a monoclonal antibody to Legionella pneumophilia serotype 1, McCarthy et al. (J. Immunol. Methods, 251(1-2): 137-149, 2001) demonstrated that a single VH CDR3 substitution of tyrosine to serine at position 95 resulted in the total loss of antigen recognition in an ELISA. Lin et al. (African Journal of Biotechnology, 10(79):18294-18302, 2011) teach that a single amino acid substitution in the VL CDR3 of an anti-avian infectious bronchitis virus (IBV) single-chain antibody (ZL.80) may abrogate binding. For example at Figure 3, Lin et al. demonstrate that replacing either the Cys105 or Asp106 residue in the VL CDR3 of ZL.80 with an alanine residue reduces binding to near negative control levels. Lin et al. also teach that some single amino acid substitutions in the VL CDR3 of ZL.80 may significantly improve binding. For example replacing the Val108 residue in the VL CDR3 of ZL.80 with a tyrosine residue results in a 12.9-fold increase in affinity compared to parental ZL.80. Accordingly absent empirical determination, one skilled in the art would be unable to predict or envision which CDR residues recited in claim 1 could be changed such that the resultant variant CDR residues form an antigen-binding site capable of binding CD160, nor could one skilled in the art envision which light and heavy chain CDRs of claim 1 would be paired such that a resultant antigen-binding domain is capable of binding to CD160. The general knowledge and level of skill in the art does not adequately supplement the omitted description, because specific, not general, guidance is needed. Since the disclosure fails to describe relevant, identifying structural characteristics, in the form of heavy and light chain CDR amino acid sequences, that correlate with the ability to bind CD160, and because the disclosed species detailed above are not sufficient to describe the claimed genus, it is submitted that the written description requirement of 35 U.S.C. 112(a) has not been met.
Although screening techniques can be used to isolate CDR variant antibodies that possess the ability to bind CD160, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also 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.”
Accordingly given the unpredictability associated with antibody CDR region changes on antigen binding and given the lack of particularity with which the claimed antibodies are described in the specification, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the specification would not reasonably convey to the skilled artisan that Applicant was in possession of the claimed invention at the time the application was filed.
Conclusion
No claim is allowed.
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/J.K.D./Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642