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 .
Priority
1. The present application claims benefit from PCT/US2020/054063 filed on 10/2/2020 which claims benefit of provisional application 62/910,594 filed on 10/4/2019. The present application was reviewed and priority was granted to provisional application 62/910,594 was granted and the effective filing date was given of 10/4/2019.
Election/Restrictions
2. The Election filed December 15, 2025, in response to the Office Action of October 24, 2025, is acknowledged and has been entered.
Applicants elected without traverse Group I. Claims 1, 2, 5, 10, 11, 14, 21-26, 35, 36, 39, 42, 44, and 46 are pending. Claims 21-23, 25, 35-36, 39, 42, 44, and 46 have been withdrawn from further consideration by the examiner under 35 CFR 1.142(b) as being drawn to non-elected inventions.
Claims 1, 2, 5, 10, 11, 14, 24, and 26 are currently under prosecution as drawn to the elected species of:
anti-KIR3DL3 antibody
comprising the six CDRs:
VH CDR 1: SEQ ID NO: 67
VH CDR2: SEQ ID NO: 69
VH CDR3: SEQ ID NO: 71
VL CDR1: SEQ ID NO: 73
VL CDR2: SEQ ID NO: 75
VL CDR3: SEQ ID NO: 77;
And the following variable regions:
VH SEQ ID NO:79
VL SEQ ID NO:81.
Bispecific antibody binding to PD-1,
wherein the PD-1 antibody comprises:
VH SEQ ID NO:141
VL SEQ ID NO:142
Claim Objections
3. Claim 11 is objected to because of the following informalities: in part b) “a VH” should be “a VL”. Appropriate correction is required.
Specification
4. The specification is objected to for improper sequence disclosure. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831. Specifically, there are no SEQ ID NOs identified with the sequences disclosed in Tables 2 and 7-9.
37 CFR 1.831 (c) requires that a reference to a particular sequence identifier (i.e., SEQ ID NO:#) be made in the specification and drawings wherever a reference is made to that sequence:
(c) Where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing XML" in accordance with paragraph (a) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by "SEQ ID NO:" or the like in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application.
Appropriate correction is required.
5. The specification is objected to due to lack of information. On pages 4-6, 68, and 70 there are blanks listed in reference to hybridoma lines and deposit accession numbers. For example, from page 4, “…hybridoma ______ deposited under deposit accession number ______.” Appropriate correction is required.
Claim Interpretation
6. The examiner’s broadest reasonable interpretation of the claims is set forth below.
Claims 1 and 10 recite:
“A [monoclonal/bispecific] antibody, or antigen-binding fragment thereof, comprising:
a) a VH comprising a VH CDR1 amino acid sequence of SEQ ID NO: 67, a VH CDR2 amino acid sequence of SEQ ID NO: 69, a VH CDR3 amino acid sequence of SEQ ID NO: 71; and
a VL comprising a VL CDR1 amino acid sequence of SEQ ID NO: 73, a VL CDR2 amino acid of SEQ ID NO: 75, and a VL CDR3 amino acid sequence of SEQ ID NO: 77.”
The phrases “a VH comprising a VH CDR1 amino acid sequence of SEQ ID NO: 67, a VH CDR2 amino acid sequence of SEQ ID NO: 69, a VH CDR3 amino acid sequence of SEQ ID NO: 71, and a VL comprising a VL CDR1 amino acid sequence of SEQ ID NO: 73, a VL CDR2 amino acid of SEQ ID NO: 75, and a VL CDR2 amino acid sequence of SEQ ID NO: 77,” are reasonably interpreted as a [monoclonal/bispecific] antibody or antigen-binding fragment comprising a VH and a VL region comprising a CDR1, CDR2, and CDR3 region where each CDR region comprises any sequence found in the corresponding SEQ ID NOs, as few as two consecutive amino acids long.
Claims 2 and 11 recite:
“The [monoclonal/bispecific] antibody, or antigen-binding fragment thereof, of claim [1/10], wherein the monoclonal antibody, or antigen-binding fragment thereof, comprises:
a) a VH comprising an amino acid sequence of SEQ ID NO: 79; and
b) a VL comprising an amino acid sequence of SEQ ID NO: 81.”
The phrases, “a VH comprising an amino acid sequence of SEQ ID NO: 79; and a VL comprising an amino acid sequence of SEQ ID NO: 81” are reasonably interpreted as a [monoclonal/bispecific] antibody or antigen-binding fragment comprising a VH region and a VL region comprising any sequence found in the corresponding SEQ ID NOs, as few as two consecutive amino acids long.
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.
7. Claims 1-2, 5, 10-11, 14, 24, and 26 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to a monoclonal or bispecific antibody, wherein the antibody comprises a VH and VL region comprising CDR1, CDR2, and CDR3 regions; wherein: the VH comprises CDR1, CDR2 and CDR3 with any amino acid sequences found in SEQ ID NOs: 67, 69 and 71, respectively; and the VL comprises CDR1, CDR2, and CDR3 with any amino acid sequences found in SEQ ID NOs: 73, 75, and 77, respectively.
Thus, the claims identify the antibody by the partial sequence structure that comprises a VH region comprising a CDR1, CDR2, and CDR3 with any amino acid sequence as few as two consecutive amino acids as set forth in SEQ ID NOs: 67, 69, and 71, respectively and further comprising a VL region comprising a CDR1, CDR2, and CDR3 with any amino acid sequence as few as two consecutive amino acids as set forth in SEQ ID NOs: 73, 75, and 77, respectively. Thus, the claims encompass a vast genus of antibody variants comprising variable VH and VL regions comprising variable CDR1, CDR2, and CDR3 sequences.
Claims 5 and 14 further require the antibody to bind KIR3DL3.
The instant specification discloses nine structurally distinct mouse monoclonal antibodies that function to bind to KIR3DL3 in Table 2:
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406
540
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The instant specification discloses antibody 1G7 as comprising the complete set of VH and VL CDR SEQ ID NOs:67, 69, 71, 73, 75, and 77 on page 75:
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628
800
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No sequence variants of antibody 1G7 are disclosed, and that predictably functions to bind KIR3DL3.
The instant specification also discloses a structurally distinct monoclonal antibody structure and a scFv protein directed towards binding KIR3DL3 that comprise the full CDR SEQ ID NOs claimed. (See Tables 7 and 8). The instant specification further discloses one structurally distinct monoclonal antibody and scFv protein directed towards binding PD-1. (See Tables 7 and 8). The instant specification also discloses one structurally distinct bispecific antibody directed towards binding to KIR3DL3 and PD-1. (See Table 9). The specification discloses antibodies comprising the claimed sequences only in the context of functioning to bind KIR3DL3.
Thus, the instant specification discloses nine structurally distinct mouse monoclonal antibodies, that comprise the full CDR SEQ ID NOs claimed and function to bind to KIR3DL3. The specification fails to disclose antibody sequence variants having as few as two consecutive amino acids found in VH and VL SEQ ID NOs: 79 and 81, or found in any of VH and VL CDR SEQ ID NOs: 67, 69, 71, 73, 75, and 77, and that function to bind KIR3DL3. The specification also fails to disclose any exemplary human antibody comprising the claimed CDR or variable region sequences.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative antibody variants, 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.).
In this case, the present claims recite a genus of antibody sequence variants that are claimed and contemplated in the specification to bind KIR3DL3. The instant specification fails to describe structural features common to the members of the antibody genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose representative antibody variant sequences that function as claimed and are contemplated by the specification. The specification discloses nine structurally distinct antibodies that all bind to KIR3DL3. The instant specification fails to describe a representative number of antibody sequence variants for the genus of antibodies 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 make the claimed antibodies.
The claims broadly encompass any monoclonal or bispecific antibody comprising sequence variant having as few as two amino acids from the VH region comprising CDR1, CDR2, and CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 67, 69, and 71 and the VL region comprising CDR1, CDR2, and CDR3 comprising the amino acid sequences set forth in SEQ ID NOs: 73, 75, and 77. Applicants have not established any reasonable structure-function correlation with regards to the sequences in the CDRs that can be altered and maintain KIR3DL3 binding function. 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 monoclonal or bispecific antibody comprising VH CDR1, CDR2, and CDR3 SEQ ID NOs: 67, 69, and 71 and VL CDR1, CDR2, and CDR3 SEQ ID NOs: 73, 75, and 77 to the structure of any variants as broadly claimed. Therefore, one could not readily envision members of the broadly claimed genus.
Although Applicants may argue that it is possible to screen for antibodies that function to bind KIR3DL3 as claimed and contemplated by the specification, 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 and contemplated. The KIR3DL3 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 variant antibodies, and lack of reasonable structure-function correlation with regards to the unknown variable sequences in the CDRs for the monoclonal or bispecific antibody variants required to bind KIR3DL3, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibody variants for monoclonal or bispecific antibodies that comprise as few as two defined consecutive amino acids in each SEQ ID NOs: 67, 69, 71, 73, 75, and 77 that is required to practice the claimed invention.
Examiner Suggestion: Examiner suggests amending claims to recite:
Claim 1: A monoclonal antibody, or antigen-binding fragment thereof, comprising a VH comprising the VH CDR1 amino acid sequence of SEQ ID NO:67, the VH CDR2 amino acid sequence of SEQ ID NO:69, the VH CDR3 amino acid sequence of SEQ ID NO:71; and a VL comprising the VL CDR1 amino acid sequence of SEQ ID NO:73, the VL CDR2 amino acid sequence of SEQ ID NO:75, and the VL CDR3 amino acid sequence of SEQ ID NO:77.
Claim 2: The monoclonal antibody, or antigen-binding fragment thereof, of claim 1 comprising:
a) a VH comprising the amino acid sequence of SEQ ID NO:79; and
b) a VL comprising the amino acid sequence of SEQ ID NO:81.
Claim 10: A bispecific antibody, or antigen-binding fragment thereof, comprising a VH comprising the VH CDR1 amino acid sequence of SEQ ID NO:67, the VH CDR2 amino acid sequence of SEQ ID NO:69, the VH CDR3 amino acid sequence of SEQ ID NO:71; and a VL comprising the VL CDR1 amino acid sequence of SEQ ID NO:73, the VL CDR2 amino acid sequence of SEQ ID NO:75, and the VL CDR3 amino acid sequence of SEQ ID NO:77.
Claim 11: The bispecific antibody, or antigen-binding fragment thereof, of claim 10 comprising:
a) a VH comprising the amino acid sequence of SEQ ID NO:79; and
b) a VL comprising the amino acid sequence of SEQ ID NO:81.
8. Claims 5 and 14 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.
The claims are drawn to a fully human antibody.
The specification discloses producing the claimed antibodies in mice, therefore the CDR sequences are murine.
Given the claimed antibody sequences are murine, they are not enabled to be human.
Examiner suggestion: Delete the option of “human” from claims 5(i) and 14(i).
Relevant Prior Art
9. The closest prior art made of record but not relied upon is Trundley (Immunogenetics (2006), 57:904-916). Trundley discloses the molecular characterization of KIR3DL3 in part by using an anti-KIR3DL3 monoclonal antibody, CH21. (See Trundley, abstract). Trundley discloses the monoclonal antibodies were then used in flow cytometry assays to screen for the presence of KIR3DL3 on the cell surface. Further, Trundley teaches that CH21 is specific for the KIR3DL3 molecule. (See Trundley, pg. 910, column 2).
Trundley does not disclose the antibody comprises the amino acid sequences instantly claimed in claims 1-2 and 10-11. Trundley also does not disclose a bispecific antibody to KIR3DL3 as claimed in claims 10 and 14.
Conclusion
10. Claims 1-2, 5, 10-11, 14, 24, and 26 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LINDSAY DUNN whose telephone number is (571)272-5825. The examiner can normally be reached Monday-Friday 8-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LINDSAY DUNN/Examiner, Art Unit 1644
/Laura B Goddard/Primary Examiner, Art Unit 1642
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