B7H6 ANTIBODY AND USE THEREOF

Application No. 18/584,875

• Filed: Feb 22, 2024
• Priority: Dec 07, 2021 — CN CN 202111485380.9
  • Dec 07, 2022 — continuation of PCTCN2022137095
• Examiner: HUYNH, PHUONG N
• Assignee: Hefei Tg Immunopharma Co. Ltd.
• OA Round: 1 (Non-Final)

Office 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 .

Claims 1-20 are pending.

Applicant’s election without traverse of Group I that read on (A) SEQ ID NO: 1 to 6 as the heavy and light chain CDRs, and (B) SEQ ID NO: 15 and SEQ ID NO: 16 as the species of heavy chain variable region and light chain variable region that binds to B7H6 in the reply filed on August 14, 2026 is acknowledged.

Claims 10, 13-14 and 16-20 are withdrawn from further consideration by the examiner, 37 C.F.R. 1.142(b) as being drawn to non-elected inventions.

Claims 1-9, 11-12 and 15, drawn to an antibody capable of binding to B7H6 or antigen binding fragment thereof that read on (A) SEQ ID NO: 1 to 6 as the heavy and light chain CDRs, and (B) SEQ ID NO: 15 and SEQ ID NO: 16 as the species of heavy chain variable region and light chain variable region, are being acted upon in this Office Action.

Priority
Applicant’ claim priority to foreign CN20211485380.9 document is acknowledged.
However, said foreign CN20211485380.9 document has NOT been received by the Office.
Applicant is reminded that such priority for the instant limitations requires written description and enablement under 35 U.S.C. 112, first paragraph.
Therefore, the priority date is deemed to be the filing date of the PCT/CN2022/137095 on December 7, 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on March 13, 2026, April 7, 2025, November 13, 2024, June 18, 2024 and February 22, 2024 have been considered by the examiner and an initialed copy of the IDS is included with this Office Action.

Drawings
The drawings filed on February 22, 2024 are acceptable.

Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.

Claim Objections
Claim 1 is objected to because of the following informality: the claim uses the abbreviation “B7H6” without first defining it. To clarify the claim, applicant should first spell out the full term before using an abbreviation. Given the subject matter of the specification, the examiner presumes that "B7H6" stands for "B7 homolog 6".
Claims 1-9, and 15 are objected to because of the following informality: “SEQ ID NO.” should have been “SEQ ID NO:”. Appropriate correction is required.

Claim Rejections - 35 USC § 112
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.

Claims 1, 4, 7 and 9 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 applicant regards as the invention.
Claim 1 recites the limitation of “capable of binding to B7H6” is indefinite as it is not clear whether the recited function following this expression is a desired feature of an actual limitation. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is suggested that claim 1 be amended to recite “An isolated antibody or antigen binding fragment thereof that binds to B7 homolog 6 (B716), wherein the antibody or antigen binding fragment thereof comprising a heavy chain CDR1, a heavy chain CDR2 and a heavy chain CDR3 and a light chain CDR1, a light chain CDR2 and a light chain CDR3, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2, the heavy chain CDR1 comprises the amino acid sequence of SE ID NO: 3, the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, the light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 5 and the light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 6 or wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 8, the heavy chain CDR1 comprises the amino acid sequence of SE ID NO: 9, the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 10, the light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 11 and the light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 12”.
Claim 4 recite the limitation “selected from (i) ….selected from (ii)” in claim 1. There is insufficient antecedent basis for this limitation in the claim.

Claim 7 recites the limitation "the isolate antibody" in claim 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 9 recites the limitation of “capable of binding to B7H6” is indefinite as it is not clear whether the recited function following this expression is a desired feature of an actual limitation. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention.

Claim rejections under - 35 U.S.C. 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-9, 11-12 and 15 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.
MPEP § 2163 states that 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, 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.
Claim 1 encompasses any antibody capable of binding to B7H6 or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3, wherein
the heavy chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 1, and SEQ ID NO. 7, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 2, and SEQ ID NO. 8, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 3, and SEQ ID NO. 9, and an amino acid sequence in conservative modification form thereof;
the light chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 4, and SEQ ID NO. 10, and an amino acid sequence in conservative modification form thereof;
the light chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 5, SEQ ID NO. 11, and an amino acid sequence in conservative modification form thereof; and
the light chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 6, SEQ ID NO. 12, and an amino acid sequence in conservative modification form thereof.
Claim 2 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof comprises:
1) the heavy chain CDR1 having an amino acid sequence as set forth in SEQ ID NO. 1, the heavy chain CDR2 having an amino acid sequence as set forth in SEQ ID NO. 2, the heavy chain CDR3 having an amino acid sequence as set forth in SEQ ID NO. 3, the light chain CDR1 having an amino acid sequence as set forth in SEQ ID NO. 4, the light chain CDR2 having an amino acid sequence as set forth in SEQ ID NO. 5, and the light chain CDR3 having an amino acid sequence as set forth in SEQ ID NO. 6: or
2) the heavy chain CDR1 having an amino acid sequence as set forth in SEQ ID NO. 7, the heavy chain CDR2 having an amino acid sequence as set forth in SEQ ID NO. 8, the heavy chain CDR3 having an amino acid sequence as set forth in SEQ ID NO. 9, the light chain CDR1 having an amino acid sequence as set forth in SEQ ID NO. 10, the light chain CDR2 having an amino acid sequence as set forth in SEQ ID NO. 11, and the light chain CDR3 having an amino acid sequence as set forth in SEQ ID NO. 12.
Claim 3 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region,
(i) the heavy chain variable region comprises an amino acid sequence that is at least 80% homologous to at least one of an amino acid sequence as set forth in SEQ ID NO. 13, SEQ ID NO. 15, SEQ ID NO. 17 and SEQ ID NO. 19 and an amino acid sequence in conservative modification form thereof; and/or,
(ii) the light chain variable region comprises an amino acid sequence that is at least 80% homologous to at least one of an amino acid sequence as set forth in SEQ ID NO. 14, SEQ ID NO. 16, SEQ ID NO. 18 and SEQ ID NO. 20 and an amino acid sequence in conservative modification form thereof.
Claim 4 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the heavy chain variable region selected from (i); wherein the light chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the light chain variable region selected from (ii).
Claim 5 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof comprises:
1) an amino acid sequence of the heavy chain variable region as set forth in SEQ ID NO. 13, and an amino acid sequence of the light chain variable region as set forth in SEQ ID NO. 14;
2) an amino acid sequence of the heavy chain variable region as set forth in SEQ ID NO. 15, and an amino acid sequence of the light chain variable region as set forth in SEQ ID NO. 16 (elected species);
3) an amino acid sequence of the heavy chain variable region as set forth in SEQ ID NO. 17, and an amino acid sequence of the light chain variable region as set forth in SEQ ID NO. 18; or
4) an amino acid sequence of the heavy chain variable region as set forth in SEQ ID NO. 19, and an amino acid sequence of the light chain variable region as set forth in SEQ ID NO. 20.
6. The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof comprises:
1) an amino acid sequence of the heavy chain as set forth in SEQ ID NO. 26, and an amino acid sequence of the light chain as set forth in SEQ ID NO. 27;
2) an amino acid sequence of the heavy chain as set forth in SEQ ID NO. 28, and an amino acid sequence of the light chain as set forth in SEQ ID NO. 29;
3) an amino acid sequence of the heavy chain as set forth in SEQ ID NO. 30, and an amino acid sequence of the light chain as set forth in SEQ ID NO. 31; or
4) an amino acid sequence of the heavy chain as set forth in SEQ ID NO. 32, and an amino acid sequence of the light chain as set forth in SEQ ID NO. 33.
Claim 7 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the isolated antibody is IgG1, IgG2, or IgG4.
Claim 8 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the antibody is a monoclonal antibody, murine antibody, chimeric antibody, humanized antibody, human engineered antibody, human antibody, Fv, single chain antibody (scFv), Fab, Fab’, Fab’-SH, or F(ab’)2.
Claim 9 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof is capable of binding to the amino acid sequence as set forth in SEQ ID NO. 21.
Claim 11 encompasses a composition, comprising the antibody or antigen binding fragment thereof of claim 1, and a pharmaceutically acceptable carrier.
Claim 12 encompasses a kit for detecting B7H6 in a sample, comprising the antibody or antigen binding fragment thereof of claim 1.
Claim 15 encompasses a medicament, comprising an antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3,
wherein the heavy chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 1, and SEQ ID NO. 7, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 2, and SEQ ID NO. 8, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 3, and SEQ ID NO. 9, and an amino acid sequence in conservative modification form thereof;
the light chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 4, and SEQ ID NO. 10, and an amino acid sequence in conservative modification form thereof; the light chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 5, SEQ ID NO. 11, and an amino acid sequence in conservative modification form thereof;
and the light chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 6, SEQ ID NO. 12, and an amino acid sequence in conservative modification form thereof.
The specification discloses just two murine monoclonal antibodies 12F5 and 12G4. The antibody 12F5 comprises a heavy chain variable region and a light chain variable region wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 13 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 14, wherein the heavy chain variable region comprises a heavy chain CDR1 (HCDR1) comprises the amino acid sequence of SEQ ID NO: 1, HCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and HCDR3 comprises the amino acid sequence of SEQ ID NO:3, and wherein the light chain variable region comprises a light chain CDR1 (LCDR1) comprises the amino acid sequence of SEQ ID NO: 4, LCDR2 comprises the amino acid sequence of SEQ ID NO: 5 and LCDR3 comprises the amino acid sequence of SEQ ID NO: 6. The humanized 12F5 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 17 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 18. The murine 12F5 heavy chain comprises the amino acid sequence of SEQ ID NO: 26 and the light chain comprises the amino acid sequence of SEQ ID NO: 27. The humanized 12F5 antibody comprises a heavy chain and a light chain wherein the heavy chain comprising the amino acid sequence of SEQ ID NO: 30 and wherein the light chain comprising the amino acid sequence of SEQ ID NO: 31. The antibody 12G4 comprises a heavy chain variable region and a light chain variable region wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 15 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 16, wherein the heavy chain variable region comprises a heavy chain CDR1 (HCDR1) comprises the amino acid sequence of SEQ ID NO: 7, HCDR2 comprises the amino acid sequence of SEQ ID NO: 8, and HCDR3 comprises the amino acid sequence of SEQ ID NO:9, and wherein the light chain variable region comprises a light chain CDR1 (LCDR1) comprises the amino acid sequence of SEQ ID NO: 10, LCDR2 comprises the amino acid sequence of SEQ ID NO: 11 and LCDR3 comprises the amino acid sequence of SEQ ID NO: 12. The humanized 12G4 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 20 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 21. The murine 12G4 heavy chain comprises the amino acid sequence of SEQ ID NO: 28 and the light chain comprises the amino acid sequence of SEQ ID NO: 29. The humanized 12G4 antibody comprises a heavy chain and a light chain wherein the heavy chain comprising the amino acid sequence of SEQ ID NO: 32 and wherein the light chain comprising the amino acid sequence of SEQ ID NO: 33, see p. 20-23.
However, the specification does not describe the structure, amino acid sequence of the heavy and light chain variable regions having any conservative modification in any one or more sequences of the heavy chain CDR1 (HCDR1), HCDR2, HCDR3, light chain CDR1 (LCDR1), LCDR2 and LCDR3.
Regarding “at least one amino acid sequence selected from heavy chain CDR1, CDR2, CDR3, light chain CDR1, CDR2 and CDR3 (claim 1), the phrase “at least one amino acid sequence” encompasses one or more amino acid sequences from each heavy chain CDR1, CDR2, CDR3, light chain CDR1, CDR2 and CDR3 in the claimed antibody or antigen binding fragment thereof capable of binding to B7H6. The specification discloses antibody or antigen binding fragment thereof that binds to B7H6 comprises a heavy chain CDR1, a heavy chain CDR2 and a heavy chain CDR3 and a light chain CDR1, a light chain CDR2 and a light chain CDR3 wherein the heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 1, the heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 2, and the heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 3, wherein the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, the light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 5 and the light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 6 arranging the particular order.
The specification does not disclose antibody comprising multiple amino acid sequences for each heavy chain CDR1, CDR2, CDR3 and light chain CDR1, CDR2 and CDR3 and randomly selected from claim 1, much less any human antibody or human engineered antibody (claim 8).
Regarding any “conservative amino acid modification” in claim 1, the term “modification” encompassed substitution, deletion, addition and a combination thereof. There is insufficient guidance as to such modification. Even assuming the modification is conservative substitution within just the heavy chain CDR1 (GYTFTSYY), a conservative substitution in each position within SEQ ID NO: 1, is 8x4x8x4x8x8x4x4 or 1,048,576 possible combinations. The specification does not describe a common structure shared by members of genus antibodies, e.g., murine antibody, chimeric antibody, human antibody, human engineered antibody, Fv, scFv, Fab, Fab’, Fab’-SH or F(ab’)2 that bind to B7H6.
Regarding “an amino acid sequence” in claims 2, 3, 5, 6, the phrase “an amino acid sequence” encompasses full-length as well as any fragment thereof. The fragment can be as little as two amino acids.
Other than the full-length sequence of heavy chain CDR1, a heavy chain CDR2 and a heavy chain CDR3 and a light chain CDR1, a light chain CDR2 and a light chain CDR3 wherein the heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 1, the heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 2, and the heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 3, wherein the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, the light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 5 and the light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 6, the specification does not teach any fragment of heavy CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2 and light chain CDR3 in claim 2 or the full-length heavy chain variable region and light chain variable region in claim 5 or the full-length sequence of the heavy chain and light chain in claim 6 maintains antigen binding to B7H6, the specification does not disclose any fragment of heavy chain and light chain or any fragment of heavy chain variable domain and light chain variable domain or any fragment of any heavy chain CDRs1-3 and any fragment of any light chain CDRs still maintains 3D structure and binding to B7H6.
Regarding claim 3, the phrase “and/or” encompasses antibody or antigen binding fragment thereof comprises a heavy chain variable and a light chain variable region or the antibody or antigen binding fragment thereof comprises just heavy chain variable region or just light chain variable region. There are no disclosure of any antibody comprises just heavy just heavy chain variable region or just light chain variable region maintains binding to B7H6.
It is well established in the art that the formation of an intact antigen-binding site of all antibodies requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope.
Chiu et al (Antibodies 8: 55-80, 2019; PTO 892) teaches the amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (see p. 4, in particular). Thus, It is unlikely the claimed antibody or antigen binding fragment thereof comprises just heavy chain variable region or just light chain variable region has the required binding to B7H6.
Regarding any sequence that is at least 80% homology (claim 3) or at least 90%, 95%, 96%, 97% 98%, 99% (claim 4), the term “homology” refers to a shared evolutionary origin between two sequences such as evolved from a common ancestral gene. Further, homology is inferred from sequence similarity, but high similarity alone does not prove homology. The specification does not disclose any of the antibodies disclosed in the specification evolved from a common ancestral gene, e.g., DNA.
Even assuming the sequence is at least 80% sequence identity, there are no specific guidance as to where and what amino acid within the full-length sequence of the heavy chain variable region and the light chain variable region to be substituted, deleted, added or a combination thereof such that modified heavy chain variable region and the modified light chain variable region maintains antigen binding to B7H6.
Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al (Proc. Natl. Acad. Sci. USA 1982 Vol. 79 page 1979). Rudikoff et al teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function.
Colman et al., in Research in Immunology (145(1):33-36, 1994; PTO 892) teach single amino acid changes in an antigen can effectively abolish antibody antigen binding, see col. 1, paragraph 1, in particular.
Furthermore, Wu et al (J. Mol. Biol. 294: 151-162, 1999; PTO 892) state that, while certain residues have been identified as important for maintaining conformation, it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left col.).
Piatesi et al (ChemBio Chem 5: 460-466, 2004; PTO 892) teach the unpredictability of amino acid substitution in hapten-contacting CDR heavy chain (CDR H3) residues with binding activity (see page 462, col. 2, in particular). Piatesi et al teach replacing three contacting residues in heavy chain CDR3 in antibody 1E9 (ThrH97, ArgHlOO, and MetHlOOb) with amino acids found at the corresponding position such as tyrosine as in antibody that binds to steroid DB3, caused a threefold increase in Kd for the hapten and a fivefold decrease in Kcat, whereas arginine at the same position, as in antibody 39-All, only causes a modest increase in the apparent Km value for NEM. Piatesi et al teach unexpectedly replacing Met at position HI00b with phenylalanine resulted in seven fold increase in Kcat, from 3.7 min-1 to about 25 min-1 (see paragraph bridging pages 462 and 463, Table 1, in particular). Piatesi et al also teach even relatively conservative substitutions at AsnH35 with serine or histidine lead to major loss of activity (see page 464, col. 1, first paragraph, Table 1, in particular).
Dufner et al (Trends Biotechnol 24(11): 523-529, 2006; PTO 892) teaches "specific structural information-on the antibody to be optimized, its antigen and their interaction- is rarely available or lacks the high resolution required to determine accurately important details such as side-chain conformations, hydrogen-bonding patterns and the position of water molecules, see page 527, paragraph 1, in particular).
The specification does not describe the structure of a sufficient number of species of the genus of antibodies that bind to B7H6 or structure common to members of the genus to reasonably convey to the skilled artisan that Applicant had possession of the claimed invention at the time the application was filed.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must 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.” (see page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (see Vas-Cath at page 1116).
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Thus, the specification fails to describe these DNA sequences.
For genus claims, an adequate written description of a claimed genus requires more than a generic statement of an invention's boundaries. A patent must set forth either a representative number of species falling within the scope of the genus or structural features common to the members of the genus. Kubin, Exparte, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007); Ariad Pharms., Inc. v. Eli Lilly& Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010).
Therefore, only (1) An isolated antibody or antigen binding fragment thereof that binds to B7 homolog 6 (B716), wherein the antibody or antigen binding fragment thereof comprising a heavy chain CDR1, a heavy chain CDR2 and a heavy chain CDR3 and a light chain CDR1, a light chain CDR2 and a light chain CDR3, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2, the heavy chain CDR1 comprises the amino acid sequence of SE ID NO: 3, the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, the light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 5 and the light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 6 or wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 8, the heavy chain CDR1 comprises the amino acid sequence of SE ID NO: 9, the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 10, the light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 11 and the light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 12,
(2) the antibody or antigen binding fragment thereof above comprises a heavy chain variable region and a light chain variable region wherein a) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 13 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:14 or b) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 15 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:16, c) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 17 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:18, or d) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:20,
(3) the antibody or antigen binding fragment thereof above comprises a heavy chain and a light chain wherein a) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 26 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 27, b) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 28 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29, c) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 30 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 31, d) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 32 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 33,
(4) the antibody or antigen binding fragment thereof above, wherein the isolated antibody is IgG1, IgG2 or IgG4.
(5) the antibody or antigen binding fragment thereof above, wherein the antibody is a monoclonal antibody, a murine antibody, a chimeric antibody, a humanized antibody, an Fv, a single chain antibody (scFv), Fab, Fab’, Fab’-SH or F(ab’)2,
(6) the antibody or antigen binding fragment thereof above, wherein the antibody or antigen binding fragment thereof binds to amino acid sequence as set forth in SEQ ID NO: 21,
(7) a composition comprising any one of the antibody or antigen binding fragment thereof above and a pharmaceutically acceptable carrier, and
(8) a kit for detecting B7H6 in a sample, comprising the antibody or antigen binding fragment thereof above, but not the full breadth of the claims meets the written description provision of 35 U.S.C. § 112, first paragraph.

Claims 1-9, 11-12 and 15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for (1) An isolated antibody or antigen binding fragment thereof that binds to B7 homolog 6 (B716), wherein the antibody or antigen binding fragment thereof comprising a heavy chain CDR1, a heavy chain CDR2 and a heavy chain CDR3 and a light chain CDR1, a light chain CDR2 and a light chain CDR3, wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 1, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 2, the heavy chain CDR1 comprises the amino acid sequence of SE ID NO: 3, the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, the light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 5 and the light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 6 or wherein the heavy chain CDR1 comprises the amino acid sequence of SEQ ID NO: 7, the heavy chain CDR2 comprises the amino acid sequence of SEQ ID NO: 8, the heavy chain CDR1 comprises the amino acid sequence of SE ID NO: 9, the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 10, the light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 11 and the light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 12, (2) the antibody or antigen binding fragment thereof above comprises a heavy chain variable region and a light chain variable region wherein a) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 13 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:14 or b) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 15 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:16, c) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 17 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:18, or d) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 19 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO:20,
(3) the antibody or antigen binding fragment thereof above comprises a heavy chain and a light chain wherein a) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 26 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 27, b) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 28 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 29, c) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 30 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 31, d) the heavy chain comprises the amino acid sequence set forth in SEQ ID NO: 32 and the light chain comprises the amino acid sequence set forth in SEQ ID NO: 33,
(4) the antibody or antigen binding fragment thereof above, wherein the isolated antibody is IgG1, IgG2 or IgG4.
(5) the antibody or antigen binding fragment thereof above, wherein the antibody is a monoclonal antibody, a murine antibody, a chimeric antibody, a humanized antibody, an Fv, a single chain antibody (scFv), Fab, Fab’, Fab’-SH or F(ab’)2,
(6) the antibody or antigen binding fragment thereof above, wherein the antibody or antigen binding fragment thereof binds to amino acid sequence as set forth in SEQ ID NO: 21,
(7) a composition comprising any one of the antibody or antigen binding fragment thereof above and a pharmaceutically acceptable carrier, and
(8) a kit for detecting B7H6 in a sample, comprising the antibody or antigen binding fragment thereof above, does not reasonably provide enablement for any antibody or antigen binding fragment thereof capable of binding to B7H6 as set forth in claims 1-9, 11-12 and 15 for treating and/or preventing any and all possible B7H6-mediated disease such as any cancer or infectious disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. . In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Claim 1 encompasses any antibody capable of binding to B7H6 or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3, wherein
the heavy chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 1, and SEQ ID NO. 7, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 2, and SEQ ID NO. 8, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 3, and SEQ ID NO. 9, and an amino acid sequence in conservative modification form thereof;
the light chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 4, and SEQ ID NO. 10, and an amino acid sequence in conservative modification form thereof;
the light chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 5, SEQ ID NO. 11, and an amino acid sequence in conservative modification form thereof; and
the light chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 6, SEQ ID NO. 12, and an amino acid sequence in conservative modification form thereof.
Claim 2 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof comprises:
1) the heavy chain CDR1 having an amino acid sequence as set forth in SEQ ID NO. 1, the heavy chain CDR2 having an amino acid sequence as set forth in SEQ ID NO. 2, the heavy chain CDR3 having an amino acid sequence as set forth in SEQ ID NO. 3, the light chain CDR1 having an amino acid sequence as set forth in SEQ ID NO. 4, the light chain CDR2 having an amino acid sequence as set forth in SEQ ID NO. 5, and the light chain CDR3 having an amino acid sequence as set forth in SEQ ID NO. 6: or
2) the heavy chain CDR1 having an amino acid sequence as set forth in SEQ ID NO. 7, the heavy chain CDR2 having an amino acid sequence as set forth in SEQ ID NO. 8, the heavy chain CDR3 having an amino acid sequence as set forth in SEQ ID NO. 9, the light chain CDR1 having an amino acid sequence as set forth in SEQ ID NO. 10, the light chain CDR2 having an amino acid sequence as set forth in SEQ ID NO. 11, and the light chain CDR3 having an amino acid sequence as set forth in SEQ ID NO. 12.
Claim 3 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region,
(i) the heavy chain variable region comprises an amino acid sequence that is at least 80% homologous to at least one of an amino acid sequence as set forth in SEQ ID NO. 13, SEQ ID NO. 15, SEQ ID NO. 17 and SEQ ID NO. 19 and an amino acid sequence in conservative modification form thereof; and/or,
(ii) the light chain variable region comprises an amino acid sequence that is at least 80% homologous to at least one of an amino acid sequence as set forth in SEQ ID NO. 14, SEQ ID NO. 16, SEQ ID NO. 18 and SEQ ID NO. 20 and an amino acid sequence in conservative modification form thereof.
Claim 4 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the heavy chain variable region selected from (i); wherein the light chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the light chain variable region selected from (ii).
Claim 5 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof comprises:
1) an amino acid sequence of the heavy chain variable region as set forth in SEQ ID NO. 13, and an amino acid sequence of the light chain variable region as set forth in SEQ ID NO. 14;
2) an amino acid sequence of the heavy chain variable region as set forth in SEQ ID NO. 15, and an amino acid sequence of the light chain variable region as set forth in SEQ ID NO. 16 (elected species);
3) an amino acid sequence of the heavy chain variable region as set forth in SEQ ID NO. 17, and an amino acid sequence of the light chain variable region as set forth in SEQ ID NO. 18; or
4) an amino acid sequence of the heavy chain variable region as set forth in SEQ ID NO. 19, and an amino acid sequence of the light chain variable region as set forth in SEQ ID NO. 20.
6. The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof comprises:
1) an amino acid sequence of the heavy chain as set forth in SEQ ID NO. 26, and an amino acid sequence of the light chain as set forth in SEQ ID NO. 27;
2) an amino acid sequence of the heavy chain as set forth in SEQ ID NO. 28, and an amino acid sequence of the light chain as set forth in SEQ ID NO. 29;
3) an amino acid sequence of the heavy chain as set forth in SEQ ID NO. 30, and an amino acid sequence of the light chain as set forth in SEQ ID NO. 31; or
4) an amino acid sequence of the heavy chain as set forth in SEQ ID NO. 32, and an amino acid sequence of the light chain as set forth in SEQ ID NO. 33.
Claim 7 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the isolated antibody is IgG1, IgG2, or IgG4.
Claim 8 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the antibody is a monoclonal antibody, murine antibody, chimeric antibody, humanized antibody, human engineered antibody, human antibody, Fv, single chain antibody (scFv), Fab, Fab’, Fab’-SH, or F(ab’)2.
Claim 9 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof is capable of binding to the amino acid sequence as set forth in SEQ ID NO. 21.
Claim 11 encompasses a composition, comprising the antibody or antigen binding fragment thereof of claim 1, and a pharmaceutically acceptable carrier.
Claim 12 encompasses a kit for detecting B7H6 in a sample, comprising the antibody or antigen binding fragment thereof of claim 1.
Claim 15 encompasses a medicament, comprising an antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3,
wherein the heavy chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 1, and SEQ ID NO. 7, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 2, and SEQ ID NO. 8, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 3, and SEQ ID NO. 9, and an amino acid sequence in conservative modification form thereof;
the light chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 4, and SEQ ID NO. 10, and an amino acid sequence in conservative modification form thereof; the light chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 5, SEQ ID NO. 11, and an amino acid sequence in conservative modification form thereof;
and the light chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 6, SEQ ID NO. 12, and an amino acid sequence in conservative modification form thereof.
The specification discloses just two murine monoclonal antibodies, namely 12F5 and 12G4. The antibody 12F5 comprises a heavy chain variable region and a light chain variable region wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 13 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 14, wherein the heavy chain variable region comprises a heavy chain CDR1 (HCDR1) comprises the amino acid sequence of SEQ ID NO: 1, HCDR2 comprises the amino acid sequence of SEQ ID NO: 2, and HCDR3 comprises the amino acid sequence of SEQ ID NO:3, and wherein the light chain variable region comprises a light chain CDR1 (LCDR1) comprises the amino acid sequence of SEQ ID NO: 4, LCDR2 comprises the amino acid sequence of SEQ ID NO: 5 and LCDR3 comprises the amino acid sequence of SEQ ID NO: 6. The humanized 12F5 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 17 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 18. The murine 12F5 heavy chain comprises the amino acid sequence of SEQ ID NO: 26 and the light chain comprises the amino acid sequence of SEQ ID NO: 27. The humanized 12F5 antibody comprises a heavy chain and a light chain wherein the heavy chain comprising the amino acid sequence of SEQ ID NO: 30 and wherein the light chain comprising the amino acid sequence of SEQ ID NO: 31. The antibody 12G4 comprises a heavy chain variable region and a light chain variable region wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 15 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 16, wherein the heavy chain variable region comprises a heavy chain CDR1 (HCDR1) comprises the amino acid sequence of SEQ ID NO: 7, HCDR2 comprises the amino acid sequence of SEQ ID NO: 8, and HCDR3 comprises the amino acid sequence of SEQ ID NO:9, and wherein the light chain variable region comprises a light chain CDR1 (LCDR1) comprises the amino acid sequence of SEQ ID NO: 10, LCDR2 comprises the amino acid sequence of SEQ ID NO: 11 and LCDR3 comprises the amino acid sequence of SEQ ID NO: 12. The humanized 12G4 antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 20 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 21. The murine 12G4 heavy chain comprises the amino acid sequence of SEQ ID NO: 28 and the light chain comprises the amino acid sequence of SEQ ID NO: 29. The humanized 12G4 antibody comprises a heavy chain and a light chain wherein the heavy chain comprising the amino acid sequence of SEQ ID NO: 32 and wherein the light chain comprising the amino acid sequence of SEQ ID NO: 33, see p. 20-23.
However, the specification does not teach the structure, amino acid sequence of the heavy and light chain variable regions having any conservative modification in any one or more sequences of the heavy chain CDR1 (HCDR1), HCDR2, HCDR3, light chain CDR1 (LCDR1), LCDR2 and LCDR3.
Regarding “at least one amino acid sequence selected from heavy chain CDR1, CDR2, CDR3, light chain CDR1, CDR2 and CDR3 (claim 1), the phrase “at least one amino acid sequence” encompasses one or more amino acid sequences from each heavy chain CDR1, CDR2, CDR3, light chain CDR1, CDR2 and CDR3 in the claimed antibody or antigen binding fragment thereof capable of binding to B7H6. The specification discloses antibody or antigen binding fragment thereof that binds to B7H6 comprises a heavy chain CDR1, a heavy chain CDR2 and a heavy chain CDR3 and a light chain CDR1, a light chain CDR2 and a light chain CDR3 wherein the heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 1, the heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 2, and the heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 3, wherein the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, the light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 5 and the light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 6 in arrange the particular order.
Neither the art nor the specification teaches an antibody comprising multiple amino acid sequences for each heavy chain CDR1, CDR2, CDR3 and light chain CDR1, CDR2 and CDR3 and randomly selected from claim 1.
Regarding any “conservative amino acid modification” in claim 1, the term “modification” encompassed substitution, deletion, addition and a combination thereof. There is insufficient guidance as to such modification. Even assuming the modification is conservative substitution within just the heavy chain CDR1 (GYTFTSYY), a conservative substitution in each position within SEQ ID NO: 1, is 8x4x8x4x8x8x4x4 or 1,048,576 possible combinations. The specification does not teach a common structure shared by members of genus antibodies, e.g., murine antibody, chimeric antibody, human antibody, human engineered antibody, Fv, scFv, Fab, Fab’, Fab’-SH or F(ab’)2 that bind to B7H6.
Regarding “an amino acid sequence” in claims 2, 3, 5, 6, the phrase “an amino acid sequence” encompasses full-length as well as any fragment thereof. The fragment can be as little as two amino acids.
Other than the full-length sequence of heavy chain CDR1, a heavy chain CDR2 and a heavy chain CDR3 and a light chain CDR1, a light chain CDR2 and a light chain CDR3 wherein the heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 1, the heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 2, and the heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 3, wherein the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, the light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 5 and the light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 6, the specification does not teach any fragment of heavy CDR1, heavy chain CDR2, heavy chain CDR3, light chain CDR1, light chain CDR2 and light chain CDR3 in claim 2 or the full-length heavy chain variable region and light chain variable region in claim 5 or the full-length sequence of the heavy chain and light chain in claim 6 maintains antigen binding to B7H6, the specification does not teach any fragment of heavy chain and light chain or any fragment of heavy chain variable domain and light chain variable domain or any fragment of any heavy chain CDRs1-3 and any fragment of any light chain CDRs still maintains 3D structure and binding to B7H6.
Regarding claim 3, the phrase “and/or” encompasses antibody or antigen binding fragment thereof comprises a heavy chain variable and a light chain variable region or the antibody or antigen binding fragment thereof comprises just heavy chain variable region or just light chain variable region.
It is well established in the art that the formation of an intact antigen-binding site of all antibodies requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope.
Chiu et al (Antibodies 8: 55-80, 2019; PTO 892) teaches the amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (see p. 4, in particular). Thus, It is unlikely the claimed antibody or antigen binding fragment thereof comprises just heavy chain variable region or just light chain variable region has the required binding to B7H6.
Regarding any sequence that is at least 80% homology (claim 3) or at least 90%, 95%, 96%, 97% 98%, 99% (claim 4), the term “homology” refers to a shared evolutionary origin between two sequences such as evolved from a common ancestral gene. Further, homology is inferred from sequence similarity, but high similarity alone does not prove homology. The specification does not teach any of the antibodies disclosed in the specification evolved from a common ancestral gene, e.g., DNA.
Even assuming the sequence is at least 80% sequence identity, there is no specific guidance as to where and what amino acid within the full-length sequence of the heavy chain variable region and the light chain variable region to be substituted, deleted, added or a combination thereof such that modified heavy chain variable region and the modified light chain variable region maintains antigen binding to B7H6.
Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al (Proc. Natl. Acad. Sci. USA Vol. 79 page 1979, 1982; PTO 892). Rudikoff et al teach that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function.
Colman et al., in Research in Immunology (145(1):33-36, 1994; PTO 892) teach single amino acid changes in an antigen can effectively abolish antibody antigen binding, see col. 1, paragraph 1, in particular.
Furthermore, Wu et al (J. Mol. Biol. 294: 151-162, 1999; PTO 892) state that, while certain residues have been identified as important for maintaining conformation, it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left col.).
Dufner et al (Trends Biotechnol 24(11): 523-529, 2006; PTO 892) teaches "specific structural information-on the antibody to be optimized, its antigen and their interaction- is rarely available or lacks the high resolution required to determine accurately important details such as side-chain conformations, hydrogen-bonding patterns and the position of water molecules, see page 527, paragraph 1, in particular).
There are no in vivo working example. It is unpredict which antibody or antigen binding fragment thereof is effective for treating which B7H6 disease, much less preventing any and all possible B7H6-mediated disease such as cancer or infectious disease.
As such, it would require undue experimentation of one skilled in the art to practice the claimed invention commensurate in scope with the claims.

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.

(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.

Claims 3 and 4 are rejected under 35 U.S.C. 102 (a)(2)as being anticipated by US 12,215,163 patent (claimed priority to 62/767,405, filed November 14, 2018; PTO 892).

Claim 3 encompasses any antibody capable of binding to B7H6 or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3, wherein
the heavy chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 1, and SEQ ID NO. 7, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 2, and SEQ ID NO. 8, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 3, and SEQ ID NO. 9, and an amino acid sequence in conservative modification form thereof;
the light chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 4, and SEQ ID NO. 10, and an amino acid sequence in conservative modification form thereof;
the light chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 5, SEQ ID NO. 11, and an amino acid sequence in conservative modification form thereof; and
the light chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 6, SEQ ID NO. 12, and an amino acid sequence in conservative modification form thereof,
wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region,
(i) the heavy chain variable region comprises an amino acid sequence that is at least 80% homologous to SEQ ID NO. 13; and/or,
(ii) the light chain variable region comprises an amino acid sequence that is at least 80% homologous to at least one of an amino acid sequence as set forth in SEQ ID NO. 14, SEQ ID NO. 16, SEQ ID NO. 18 and SEQ ID NO. 20 and an amino acid sequence in conservative modification form thereof.
Claim 4 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the heavy chain variable region selected from (i); wherein the light chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the light chain variable region selected from (ii).

The ‘163 patent teaches an antibody comprises the amino acid sequence of SEQ ID NO: 441, which has 93.4% identity to the claimed SEQ ID NO: 13, see sequence alignment below:
Query Match 92.2%; Score 594.5; Length 120;
Best Local Similarity 93.4%;
Matches 113; Conservative 4; Mismatches 3; Indels 1; Gaps 1;

Qy 1 QVQLQQSGAELVKPGASVKLSCKASGYTFTSYYMYWVKQRPGQGLEWIGEINPSNGGTNF 60
||||||||||||||||||||||||||||||::|:||||||||||||||| ||||||||||
Db 1 QVQLQQSGAELVKPGASVKLSCKASGYTFTNFYLYWVKQRPGQGLEWIGGINPSNGGTNF 60

Qy 61 NEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCTRTLYYGNDWYFDVWGAGTTVTVS 120
||||||||||||||||||||||||||||||||||||||: || ||||||||||||||||
Db 61 NEKFKSKATLTVDKSSSTAYMQLSSLTSEDSAVYYCTRS-YYDYDWYFDVWGAGTTVTVS 119

Qy 121 S 121
|
Db 120 S 120

The term “or” does not required the light chain variable region.
Although the reference does not specifically teach the antibody binds to B7H6, a chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure as claimed, the properties applicant discloses and/or claims are necessarily present. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Further, since the office does not have the facilities to compare the claimed antibody to that of the prior art, the burden is on the applicant to prove that the claimed antibody is different from that taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Thus, the reference teachings anticipate the claimed invention.

Claims 3 and 4 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by US2020/0223920 publication (published July 16, 2020; PTO 892).
Claim 3 encompasses any antibody capable of binding to B7H6 or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3, wherein
the heavy chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 1, and SEQ ID NO. 7, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 2, and SEQ ID NO. 8, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 3, and SEQ ID NO. 9, and an amino acid sequence in conservative modification form thereof;
the light chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 4, and SEQ ID NO. 10, and an amino acid sequence in conservative modification form thereof;
the light chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 5, SEQ ID NO. 11, and an amino acid sequence in conservative modification form thereof; and
the light chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 6, SEQ ID NO. 12, and an amino acid sequence in conservative modification form thereof,
wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region,
(i) the heavy chain variable region comprises an amino acid sequence that is at least 80% homologous to at least one of an amino acid sequence as set forth in SEQ ID NO. 13, SEQ ID NO. 15, SEQ ID NO. 17 and SEQ ID NO. 19 and an amino acid sequence in conservative modification form thereof; and/or,
(ii) the light chain variable region comprises an amino acid sequence that is at least 80% homologous to SEQ ID NO. 14.
Claim 4 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the heavy chain variable region selected from (i); wherein the light chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the light chain variable region selected from (ii).

The ‘920 publication teaches an antibody comprises the amino acid sequence of SEQ ID NO: 27, which has 98.6% identity to the claimed SEQ ID NO: 14, see sequence alignment below, the light chain CDRs 1-3 are in bold, respectively, and comprises conservative substitution in the claimed CDR1 of SEQ ID NO: 4 and CDR3 of SEQ ID NO: 6:
Query Match 98.6%; Score 544; Length 106;
Best Local Similarity 98.1%;
Matches 104; Conservative 2; Mismatches 0; Indels 0; Gaps 0;

Qy 1 QIVLTQSPAIMSASPGEKVTMTCSASSSVNYMHWYQQKSGTSPKRWIYDTSKLASGVPAR 60
|||||||||||||||||||||||||||||:||||||||||||||||||||||||||||||
Db 1 QIVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSGTSPKRWIYDTSKLASGVPAR 60

Qy 61 FSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPVTFGAGTKLELK 106
||||||||||||||||||||||||||||||||||:|||||||||||
Db 61 FSGSGSGTSYSLTISSMEAEDAATYYCQQWSSNPLTFGAGTKLELK 106

The term “or” does not required the heavy chain variable region.
Although the reference does not specifically teach the antibody binds to B7H6, a chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure as claimed, the properties applicant discloses and/or claims are necessarily present. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Further, since the office does not have the facilities to compare the claimed antibody to that of the prior art, the burden is on the applicant to prove that the claimed antibody is different from that taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Thus, the reference teachings anticipate the claimed invention.

Claims 3 and 4 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by US patent No 8,858,949 (Issued Oct 14, 2014; PTO 892).
Claim 3 encompasses any antibody capable of binding to B7H6 or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3, wherein
the heavy chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 1, and SEQ ID NO. 7, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 2, and SEQ ID NO. 8, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 3, and SEQ ID NO. 9, and an amino acid sequence in conservative modification form thereof;
the light chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 4, and SEQ ID NO. 10, and an amino acid sequence in conservative modification form thereof;
the light chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 5, SEQ ID NO. 11, and an amino acid sequence in conservative modification form thereof; and
the light chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 6, SEQ ID NO. 12, and an amino acid sequence in conservative modification form thereof,
wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region,
(i) the heavy chain variable region comprises an amino acid sequence that is at least 80% homologous to at least one of an amino acid sequence as set forth in SEQ ID NO. 13, SEQ ID NO. 15, SEQ ID NO. 17 and SEQ ID NO. 19 and an amino acid sequence in conservative modification form thereof; and/or,
(ii) the light chain variable region comprises an amino acid sequence that is at least 80% homologous to SEQ ID NO. 16.
Claim 4 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the heavy chain variable region selected from (i); wherein the light chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the light chain variable region selected from (ii).

The ‘949 patent teaches an antibody comprises the amino acid sequence of SEQ ID NO: 2880, which has 93.7% identity to the claimed SEQ ID NO: 16:
Query Match 93.7%; Score 548; Length 111;
Best Local Similarity 93.7%;
Matches 104; Conservative 1; Mismatches 6; Indels 0; Gaps 0;

Qy 1 DIVLTQSPVSLAVPLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAASTLHS 60
|||||||| |||| |||||||||||||||||||||||||||||||||||||||||| | |
Db 1 DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAASNLES 60

Qy 61 GIPVRFSGSGSGTDFTLNIHPVEEEDAASYYCQQSKEDPRTFGGGTKLEIK 111
||| ||||||||||||||||||||||||:|||||| |||||||||||||||
Db 61 GIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPRTFGGGTKLEIK 111

The term “or” does not required the heavy chain variable region.
Although the reference does not specifically teach the antibody binds to B7H6, a chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure as claimed, the properties applicant discloses and/or claims are necessarily present. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Further, since the office does not have the facilities to compare the claimed antibody to that of the prior art, the burden is on the applicant to prove that the claimed antibody is different from that taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Thus, the reference teachings anticipate the claimed invention.

Claims 3 and 4 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by US patent No 8,945,553 (Issued February 3, 2015; PTO 892).
Claim 3 encompasses any antibody capable of binding to B7H6 or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2, and a light chain CDR3, wherein
the heavy chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 1, and SEQ ID NO. 7, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 2, and SEQ ID NO. 8, and an amino acid sequence in conservative modification form thereof;
the heavy chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 3, and SEQ ID NO. 9, and an amino acid sequence in conservative modification form thereof;
the light chain CDR1 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 4, and SEQ ID NO. 10, and an amino acid sequence in conservative modification form thereof;
the light chain CDR2 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 5, SEQ ID NO. 11, and an amino acid sequence in conservative modification form thereof; and
the light chain CDR3 comprises at least one amino acid sequence selected from the group consisting of an amino acid sequence as set forth in SEQ ID NO. 6, SEQ ID NO. 12, and an amino acid sequence in conservative modification form thereof,
wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region and a light chain variable region,
(i) the heavy chain variable region comprises an amino acid sequence that is at least 80% homologous to at least one of an amino acid sequence as set forth in SEQ ID NO. 13, SEQ ID NO. 15, SEQ ID NO. 17 and SEQ ID NO. 19 and an amino acid sequence in conservative modification form thereof; and/or,
(ii) the light chain variable region comprises an amino acid sequence that is at least 80% homologous to SEQ ID NO. 18 and an amino acid sequence in conservative modification form thereof.
Claim 4 encompasses the antibody or antigen binding fragment thereof of claim 1, wherein the heavy chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the heavy chain variable region selected from (i); wherein the light chain variable region comprises an amino acid sequence that is at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% homologous to the light chain variable region selected from (ii).

The ‘553 patent teaches an antibody comprises the amino acid sequence of SEQ ID NO: 39, which has 94.4% identity to the claimed SEQ ID NO: 18:
Query Match 94.4%; Score 525; Length 106;
Best Local Similarity 94.3%;
Matches 100; Conservative 4; Mismatches 2; Indels 0; Gaps 0;

Qy 1 EIVLTQSPDFQSVTPKEKVTITCSASSSVNYMHWYQQKPDQSPKRLIYDTSKLASGVPSR 60
|||||||||||||||||||||||||||||||||||||||||||| || ||||||||||||
Db 1 EIVLTQSPDFQSVTPKEKVTITCSASSSVNYMHWYQQKPDQSPKLLIKDTSKLASGVPSR 60

Qy 61 FSGSGSGTDYTLTINSLEAEDAATYYCQQWSSNPVTFGQGTKLEIK 106
|||||||||:||||||||||||||||||||:|:|:|||||||||||
Db 61 FSGSGSGTDFTLTINSLEAEDAATYYCQQWNSHPLTFGQGTKLEIK 106

The term “or” does not required the heavy chain variable region.
Although the reference does not specifically teach the antibody binds to B7H6, a chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure as claimed, the properties applicant discloses and/or claims are necessarily present. "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Further, since the office does not have the facilities to compare the claimed antibody to that of the prior art, the burden is on the applicant to prove that the claimed antibody is different from that taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Thus, the reference teachings anticipate the claimed invention.

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.

Claims 1-5, 7-9, 11-12 and 15 are provisionally rejected on the ground of nonstatutory double patenting over claims 1-20 of copending Application No. 18/389,819 (reference, now allowed). This is a provisional double patenting rejection because the patentably indistinct claims have not in fact been patented.
The subject matter claimed in the instant application is fully disclosed in the referenced copending application and would be covered by any patent granted on that copending application since the referenced copending application and the instant application are claiming common subject matter, as follows:
The reference humanized antibody capable of binding to B7H6 comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 21, which is 100% identical to the claimed SEQ ID NO: 15, see sequence alignment, CDRs 1-3 in bold and identical to instant SEQ ID Nos 7, 8 and 9, respectively.

Query Match 100.0%; Score 639; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;

Qy 1 EVLLQQSGPEVVKPGASVKITCKASGYTFTDYNMDWVKQSHGKSLEWIGDINPNNGGTLY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVLLQQSGPEVVKPGASVKITCKASGYTFTDYNMDWVKQSHGKSLEWIGDINPNNGGTLY 60

Qy 61 NQKFRGRVTLIVDKSSSTAYMELRSLTSDDTAVYYCARSEVFYGNYADYWGQGTTLTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFRGRVTLIVDKSSSTAYMELRSLTSDDTAVYYCARSEVFYGNYADYWGQGTTLTVSS 120

And a light chain variable region comprising the amino acid sequence of SEQ ID NO: 15, which is 100% identical to the claimed SEQ ID NO: 16, see sequence alignment, CDR 1-3 are in bold and identical to instant SEQ ID Nos 10, 11 and 12.

Query Match 100.0%; Score 585; Length 111;
Best Local Similarity 100.0%;
Matches 111; Conservative 0; Mismatches 0; Indels 0; Gaps 0;

Qy 1 DIVLTQSPVSLAVPLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAASTLHS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVLTQSPVSLAVPLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAASTLHS 60

Qy 61 GIPVRFSGSGSGTDFTLNIHPVEEEDAASYYCQQSKEDPRTFGGGTKLEIK 111
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GIPVRFSGSGSGTDFTLNIHPVEEEDAASYYCQQSKEDPRTFGGGTKLEIK 111

The reference teaches single chain antibody comprises a heavy chain variable region set forth SEQ ID NO: 25, which is 100% identical to the claimed SEQ ID NO: 19, see sequence alignment below:
Query Match 100.0%; Score 638; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;

Qy 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNMDWVRQAPGKGLEWIGDINPNNGGTLY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNMDWVRQAPGKGLEWIGDINPNNGGTLY 60

Qy 61 NQKFRGRVTLTVDKSISTAYMELSRLRSDDTAVYYCARSEVFYGNYADYWGQGTTVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFRGRVTLTVDKSISTAYMELSRLRSDDTAVYYCARSEVFYGNYADYWGQGTTVTVSS 120

And a light chain variable region set forth in SEQ ID NO: 19, which is identical to the claimed SEQ ID NO: 20, see sequence alignment below:
Query Match 100.0%; Score 582; Length 111;
Best Local Similarity 100.0%;
Matches 111; Conservative 0; Mismatches 0; Indels 0; Gaps 0;

Qy 1 DIVLTQTPLSLSVTPGQPASISCKASQSVDYDGDSYMNWYLQKPGQPPQLLIYAASTLHS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVLTQTPLSLSVTPGQPASISCKASQSVDYDGDSYMNWYLQKPGQPPQLLIYAASTLHS 60

Qy 61 GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCQQSKEDPRTFGQGTKLEIK 111
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCQQSKEDPRTFGQGTKLEIK 111

This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.

Allowable Subject Matter
SEQ ID NO: 13, 14, 17, 18, 26, 27, 28, 29, 30, 31, 32 and 33 are free of prior art.

Conclusion
No claim is allowed.

Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHUONG HUYNH whose telephone number is [phone]. The examiner can normally be reached on 9:00 a.m. to 6:30 p.m. The examiner can also be reached on alternate alternative Friday from 9:00 a.m. to 5:30 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Misook Yu, can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PHUONG HUYNH/ Primary Examiner, Art Unit 1641

Prosecution Timeline

• Feb 22, 2024: Application Filed
• Aug 28, 2026: Non-Final Rejection mailed — §102, §112, §DP (current)