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 .
Election/Restrictions
1. The response filed on July 24, 2026 to the restriction requirement of June 9, 2026 has been received. Applicant has elected for examination of the species of the B7H3 monoclonal antibody comprising a HCVR of SEQ ID NO: 7 and a LCVR of SEQ ID NO: 17 and the B7H3 chimeric antigen receptor of the amino acid sequence of SEQ ID NO: 56. Because Applicant did not distinctly and specifically point out any errors in the restriction requirement, the election has been treated as an election without traverse (MPEP 818.03(a)). Claims 1-20 are pending and are currently under prosecution as drawn to the elected species.
Priority
2. Application claims the benefit and priority of PCT/CN2021/115806 filed on 8/31/2021 which claims the benefit and priority of CN202110736498.8 filed on 6/30/2021, CN202110768579.6 filed 7/7/2021, CN202110784331.9 filed on 7/12/2021, CN202110783589.7 filed on 7/12/2021, CN202110736533.6 filed on 6/30/2021, CN202110739700.2 filed on 6/30/2021, CN202110768592.1 filed on 7/7/2021, CN2021107685590.2 filed on 7/7/2021, CN202110739303.5 filed on 6/30/2021, CN202110739305.4 filed on 6/30/2021, and CN202110739693.6 filed on 6/30/2021. Priority is granted to CN202110736498.8 and the effective filing date of 6/30/2021.
Specification
3. The specification is objected to for containing the following sequence listings of SEQ ID NOs: 13 and 14. The listed sequences all contain <4 amino acids and were changed to the dummy sequence “000.” Please amend the specification to remove the “SEQ ID NO:XX” and replace with the actual amino acid sequence listing. Below are the places in the specification listing the SEQ ID NOs from above:
Page 4 lines 24-26, both; and
Page 30 line 24, SEQ ID NO: 13.
Claim Objections
4. Claim 2 is objected to based on the listing of SEQ ID NOs: 13 and 14. The sequence listings all contain <4 amino acids and were changed to dummy sequence “000.” Please amend claim 2 to remove reference to the SEQ ID NOs listed above and replace with the exact amino acid sequences.
Claim Interpretation
5. The examiner’s broadest reasonable interpretation of the claims is set forth below.
Claim 1 recites:
“An isolated fully human monoclonal antibody or an antigen-binding fragment thereof, wherein the antibody or the antigen-binding fragment thereof specifically binds to B7H3; the antibody or the antigen-binding fragment thereof comprises an HCVR and an LCVR; the HCVR comprises an HCDR1, an HCDR2 and an HCDR3; the LCVR comprises an LCDR1, an LCDR2 and an LCDR3; the HCDR1, the HCDR2 and the HCDR3 are an HCDR1, an HCDR2 and an HCDR3, respectively, in an HCVR with an amino acid sequence set forth in SEQ ID NO: 7; and the LCDR1, the LCDR2 and the LCDR3 are an LCDR1, an LCDR2 and an LCDR3, respectively, in an LCVR with an amino acid sequence set forth in SEQ ID NO: 17.”
The phrase “an amino acid sequence set forth in SEQ ID NO: [7/17]” are reasonably interpreted as a B7H3 antibody or antigen-binding fragment comprising a HCVR region and a LCVR region comprising any sequence found in SEQ ID NOs: 7 and 17, respectively, as few as two consecutive amino acid sequences long.
Claim 2 recites:
“The antibody or the antigen-binding fragment thereof according to claim 1, wherein the HCDR1 comprises an amino acid sequence set forth in SEQ ID NO: 1, or an amino acid sequence having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity to SEQ ID NO: 1; the HCDR2 comprises an amino acid sequence set forth in SEQ ID NO: 3, or an amino acid sequence having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity to SEQ ID NO: 3; the HCDR3 comprises an amino acid sequence set forth in SEQ ID NO: 5, or an amino acid sequence having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity to SEQ ID NO: 5; the LCDR1 comprises an amino acid sequence set forth in SEQ ID NO: 11, or an amino acid sequence having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity to SEQ ID NO: 11; the LCDR2 comprises an amino acid sequence set forth in SEQ ID NO: 13, or an amino acid sequence having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity to SEQ ID NO: 13; and the LCDR3 comprises an amino acid sequence set forth in SEQ ID NO: 15, or an amino acid sequence having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity to SEQ ID NO: 15.”
The phrases “[H/L]CDR[1/2/3] comprises an amino acid sequence set forth in SEQ ID NO: XX” are reasonably interpreted as the B7H3 antibody or antigen-binding fragment of claim 1 further comprising a HCVR region comprising an HCDR1, HCDR2, and HCDR3; and a LCVR region comprising a LCDR1, LCDR2, and LCDR3 comprising any sequence found in SEQ ID NOs: 1, 3, 5, 11, 13, and 15, respectively, as few as two consecutive amino acid sequences long.
Claim 3 recites:
“The antibody or the antigen-binding fragment thereof according to claim 2, wherein the HCVR of the antibody or the antigen-binding fragment thereof and the LCVR of the antibody or the antigen-binding fragment thereof are linked by a Linker; and the Linker has an amino acid sequence set forth in SEQ ID NO: 21 or SEQ ID NO: 22.”
The phrase “an amino acid sequence set forth in SEQ ID NO: 21 or SEQ ID NO: 22” is reasonably interpreted as the B7H3 antibody or antigen-binding fragment of claim 2 where the HCVR and the LCVR are linked by a linker comprising any amino acid sequence found in SEQ ID NOs: 21 or 22, as few as two amino acid sequences long.
Claim 4 recites:
“The antibody or the antigen-binding fragment thereof according to claim 3, wherein the antibody or the antigen-binding fragment thereof has an amino acid sequence set forth in SEQ ID NO: 25.”
The phrase “an amino acid sequence set forth in SEQ ID NO: 25” is reasonably interpreted as the B7H3 antibody or antigen-binding fragment of claim 3 comprising any amino acid sequence found in SEQ ID NO: 25, as few as two consecutive amino acid sequences long.
Claim 10 recites:
“The chimeric antigen receptor according to claim 9, wherein the chimeric antigen receptor is selected from any one of the group consisting of: (1) a chimeric antigen receptor with an amino acid sequence set forth in SEQ ID NO: 56.”
The phrase “an amino acid sequence set forth in SEQ ID NO: 56” is reasonably interpreted as the CAR according to claim 9 comprising any amino acid sequence set forth in SEQ ID NO: 56, as few as two consecutive amino acid sequences long.
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.
6. Claims 10, 12, and 16 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 the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 10 recites “a chimeric antigen receptor with an amino acid sequence set forth in SEQ ID NO: 56”. This phrase is indefinite because SEQ ID NO: 56 is a nucleotide sequence, not an amino acid sequence. Please amend claim 10 to recite “a chimeric antigen receptor with the nucleotide sequence set forth in SEQ ID NO: 56” to overcome this rejection.
Claim 12 recites “wherein the nucleotide sequence encoding the HCVR of the antibody or the antigen-binding fragment thereof is set forth in SEQ ID NO: 9; the nucleotide sequence encoding the LCVR of the antibody or the antigen-binding fragment thereof is set forth in SEQ ID NO: 19.” The claim is indefinite because it is unclear whether the phrase reciting the HCVR region of the antibody and the phrase reciting the LCVR region of the antibody are linked through an “and” or an “or” and thus it is unclear and indefinite about whether the claim is drawn to ‘the polynucleotide set forth in SEQ ID NO: 9 AND SEQ ID NO: 19’, or ‘the polynucleotide set forth in SEQ ID NO: 9 OR SEQ ID NO: 19’. To overcome this rejection, please amend claim 12 to recite either “and” or “or” following the semi-colon in the underlined portion above. For the sake of compact prosecution, examiner will interpret the claim to be linked with an “and”.
Claim 16 recites “A derivative,” in line 1. This phrase is unclear and indefinite because it is not clear what the subject is a derivative of- the antibody? Antigen-binding fragment? The HCVR or LCVR? The CAR? The metes and boundaries of the claim are unclear and indefinite. To overcome this rejection, please amend claim 16 to properly define the derivative.
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 1-11 and 13-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to an isolated fully human monoclonal antibody or an antigen-binding fragment that binds to B7H3 and comprises an HCVR and LCVR with amino acid sequences as set forth in SEQ ID NOs: 7 and 17, respectively.
Claim 2 further defines the claims as the HCVR comprising a HCDR1, HCDR2, and HCDR3 and the LCVR as comprising a LCDR1, LCDR2, and LCDR3 with amino acid sequences as set forth in SEQ ID NOs: 1, 3, 5, 11, 13, and 15, respectively.
Claim 3 further defines the antibody or antigen-binding fragment sequences comprising the HCVR and LCVR linked together through the amino acid sequences set forth in SEQ ID NO: 21 and 22.
Claim 4 further defines the antibody or antigen-binding fragment sequences with amino acid sequences set forth in SEQ ID NO: 25.
Claims 5-10 are further drawn to a fully human chimeric antigen receptor (CAR) comprising the B7H3 antibody and as defined in claim 10 with the nucleotide sequences set forth in SEQ ID NO: 56.
As stated above in the “Claim Interpretation” section, these claims broadly encompass any amino acid sequences of the recited SEQ ID NOs as small as two consecutive amino acids long.
Thus, the claims identify the antibody or antigen-binding fragment by the function of binding to B7H3 and a partial sequence structure comprising the HCVR region and the LCVR region with any amino acid sequences as few as two consecutive amino acid sequences as set forth in SEQ ID NOs: 7 and 17, respectively. The claims also identify the CAR by the function of binding to B7H3 and a partial sequence structure of any nucleotide sequence as few as two consecutive nucleotide sequences as set forth in SEQ ID NO: 56. Thus, the claims encompass a vast genus of antibody and CAR variants comprising variable HCVR, LCVR, and CAR sequences required to bind B7H3.
The instant specification discloses two structurally distinct B7H3 antigen-binding regions comprising structurally distinct HCVRs with distinct HCDR1, HCDR2, and HCDR3 and structurally distinct LCVRs with distinct LCDR1, LCDR2, and LCDR3. (See pg. 4 line 7- pg. 5 line 6).
The instant specification discloses 7 structurally distinct B7H3 CARs. (See pg. 9 line 31- pg. 10 line 5).
Thus, the instant specification discloses distinct structural sequences of 2 B7H3 antigen-binding domains with the complete amino acid structure of the HCVRs and their respective HCDR1, HCDR2, and HCDR3 and the complete amino acid structure of the LCVRs and their respective LCDR1, LCDR2, and LCDR3. The specification fails to disclose any other HCVR or LCVR sequence variants having as few as two consecutive amino acids found in SEQ ID NOs: 7 and 17 that possess the function of binding B7H3. The specification fails to disclose any other CAR sequence variants having as few as two nucleotide sequences that possess the function of binding B7H3.
To provide adequate written description and evidence of the claimed antibody or CAR genus, the instant specification can structurally describe representative antibody or CAR variants that function to bind B7H3, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
In this case, the only factor present in the claims is a recitation of the antibody and CAR function, “binds to B7H3”, and partial sequence structure as stated above. The instant specification fails to describe structural features common to the members of the antibody and CAR genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose representative antibody and CAR variant sequences that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. Other than for the antibodies and CAR sequences disclosed in the specification, the specification fails to provide the HCVR, LCVR, and CAR structural features coupled to the claimed functional characteristics. The instant specification fails to describe the representative number of antibody and CAR sequence variants for the genus of antibodies and CARs that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to make the claimed antibodies or CARs.
The claims broadly encompass any sequence variant having as few as two consecutive amino acids from HCVR and LCVR of SEQ ID NOs: 7 and 17 that function to bind B7H3. Applicants have not established any reasonable structure-function correlation with regards to the sequences in the CDRs that can be altered and still maintain B7H3 binding function. Sela-Culang et al. (Frontiers in Immunol., 2013, 4:302) teaches that antibody CDRs have a unique set of contact preferences, favoring certain amino acids over others. (See Sela-Culang, pgs. 5-6). Given the well-known high level of polymorphism of antibody CDR sequences and structure required for HCVR and LCVR binding to occur, the skilled artisan would not have been in possession of the vast repertoire of antibodies or CARs encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a single antibody comprising amino acid sequences of SEQ ID NOs: 7 and 17 to the structure of any variants required to bind B7H3 as broadly claimed. One could not reasonably or predictably extrapolate the structure of a single CAR comprising SEQ ID NO: 56 to the structure of any variants required to bind B7H3 as broadly claimed. Therefore, one could not readily envision the members of the broadly claimed genus.
Although Applicants may argue that it is possible to screen for antibodies or CARs that bind B7H3 and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies or CARs yet to be discovered that may function as claimed. The B7H3 antigen provides no information about the structure of an antibody or CAR that binds to it.
Given the lack of representative examples to support the full scope of the claimed variant antibodies and CARs, and lack of reasonable structure-function correlation with regards to the unknown variable sequences in the HCVR, LCVR, and CAR structure that provide B7H3-binding function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibody and CAR variants that bind B7H3 and comprise as few as two defined consecutive amino acids in each HCVR and LCVR from SEQ ID NOs: 7 and 17 or as few as two consecutive nucleotide sequences in SEQ ID NO: 56 that is required to practice the claimed invention.
Examiner Suggestion: Examiner suggests amending claim 1 to recite:
“An isolated fully human monoclonal antibody or an antigen-binding fragment thereof, wherein the antibody or the antigen-binding fragment thereof specifically binds to B7H3;
the antibody or the antigen-binding fragment thereof comprises an HCVR and an LCVR;
the HCVR comprises an HCDR1, an HCDR2 and an HCDR3;
the LCVR comprises an LCDR1, an LCDR2 and an LCDR3;
the HCDR1, the HCDR2 and the HCDR3 are an HCDR1, an HCDR2 and an HCDR3, respectively, in an HCVR with the amino acid sequence set forth in SEQ ID NO: 7 or SEQ ID NO: 8; and the LCDR1, the LCDR2 and the LCDR3 are an LCDR1, an LCDR2 and an LCDR3, respectively, in an LCVR with the amino acid sequence set forth in SEQ ID NO: 17 or SEQ ID NO: 18.”
Examiner suggests amending claim 10 to recite:
“The chimeric antigen receptor according to claim 9, wherein the chimeric antigen receptor is selected from any one of the group consisting of: (1) a chimeric antigen receptor with the nucleotide
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)(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.
8. Claims 1-2, 11, and 13-20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zhang (WO2021/213478, effective filing date 4/22/2020).
Zhang discloses a monoclonal antibody against B7H3 (See pg. 3 [0005]) that is fully human (See pg. 4 [0032]) comprising a heavy chain variable region comprising three CDR regions and a light chain variable region comprising three CDR regions (See pg. 3 [0006]-[0007]). Zhang also discloses a heavy chain variable region that is 92.9% identical to SEQ ID NO: 7 and comprises an amino acid sequence of the HCDR1, HCDR2, and HCDR3 of SEQ ID NOs: 1, 3, and 5; and a light chain variable region that is 93% identical to SEQ ID NO: 17 and comprises amino acid sequences of the LCDR1, LCDR2, and LCDR3 of SEQ ID NOs: 11, 13, and 15. (See pg. 8 [0073] Table 0001 Serial Number 3, also alignments below).
Regarding claims 11 and 13-17, Zhang discloses the B7H3 antibody encoded by a polynucleotide and can be expressed through a recombinant vector in an engineered host cell including immune cells like NK cells and T cells. (See Zhang pg. 9 [0086]-[0088], [0090]-[0093], [0099]). Zhang also discloses the antibody can be conjugated to a detectable label and drugs. (See Zhang pg. 9 [0096]). Zhang also discloses the antibody can be in pharmaceutical composition comprising the engineered host cell. (See Zhang pgs. 9 [0102]).
Regarding claims 18-20, Zhang discloses the antibody can be used in a method for detecting B7H3 in a test sample comprising contacting the antibody with the sample and detecting the formation of a complex by the antibody or the antigen-binding fragment thereof and B7H3 or in a method for treating diseases related to B7H3 expression including cancer and specifically lung cancer, prostate cancer, breast cancer, colorectal cancer, kidney cancer, ovarian cancer, and liver cancer. (See Zhang pgs. 10-11 [0108]-[0113], [0116]-[0117], [0121]-[0123]).
SEQ ID NO: 7 is 92.9% identical to SEQ ID NO: 17 (Zhang):
WO2021213478-A1.
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CC PD 28-OCT-2021.
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CC PF 22-APR-2021; 2021WO-CN089086.
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PR 22-APR-2020; 2020CN-10324347.
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CC PA (FOSU-) FOSUN KITE BIOTECHNOLOGY CO LTD.
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CC PI Zhang L, Xu M, Gao M;
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DR WPI; 2021-C1216E/092.
DR N-PSDB; BKD85853.
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CC PT New anti-B7-H3 antibody comprising e.g. heavy chain and light chain
CC PT variable regions with complementarity determining regions useful e.g. in
CC PT preparing kit, and medicine for treating diseases associated with B7-H3
CC PT expression or dysfunction.
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CC PS Claim 2; SEQ ID NO 17; 74pp; Chinese.
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SQ Sequence 116 AA;
Query Match 92.9%; Score 569.5; Length 116;
Best Local Similarity 94.0%;
Matches 110; Conservative 3; Mismatches 3; Indels 1; Gaps 1;
Qy 1 EVQLFQSGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
|||| :||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYY 60
Qy 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGVGRGFDYWGQGTTVTVSS 117
|||||||||||||||||||||||||||||||||||||:||| :||||||| |||||
Db 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKGVG-AYDYWGQGTLVTVSS 116
SEQ ID NOs: 1, 3, and 5 represented in SEQ ID NO: 17 (Zhang):
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CC PD 28-OCT-2021.
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PR 22-APR-2020; 2020CN-10324347.
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CC PA (FOSU-) FOSUN KITE BIOTECHNOLOGY CO LTD.
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CC PI Zhang L, Xu M, Gao M;
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DR WPI; 2021-C1216E/092.
DR N-PSDB; BKD85853.
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CC PT New anti-B7-H3 antibody comprising e.g. heavy chain and light chain
CC PT variable regions with complementarity determining regions useful e.g. in
CC PT preparing kit, and medicine for treating diseases associated with B7-H3
CC PT expression or dysfunction.
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CC PS Claim 2; SEQ ID NO 17; 74pp; Chinese.
Query Match 61.3%; Score 83.4; Length 116;
Best Local Similarity 27.2%;
Matches 22; Conservative 2; Mismatches 1; Indels 56; Gaps 3;
Qy 1 GFTFSSY-----------------AISGSGGST--------------------------- 16
||||||| |||||||||
Db 26 GFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNS 85
Qy 17 -----------ARGVGRGFDY 26
|:||| :||
Db 86 LRAEDTAVYYCAKGVG-AYDY 105
SEQ ID NO: 17 is 93.0% identical to SEQ ID NO: 21 (Zhang):
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CC PD 28-OCT-2021.
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PR 22-APR-2020; 2020CN-10324347.
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CC PA (FOSU-) FOSUN KITE BIOTECHNOLOGY CO LTD.
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CC PI Zhang L, Xu M, Gao M;
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DR WPI; 2021-C1216E/092.
DR N-PSDB; BKD85852.
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CC PT New anti-B7-H3 antibody comprising e.g. heavy chain and light chain
CC PT variable regions with complementarity determining regions useful e.g. in
CC PT preparing kit, and medicine for treating diseases associated with B7-H3
CC PT expression or dysfunction.
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CC PS Claim 4; SEQ ID NO 21; 74pp; Chinese.
Query Match 93.0%; Score 521; Length 108;
Best Local Similarity 92.6%;
Matches 100; Conservative 5; Mismatches 3; Indels 0; Gaps 0;
Qy 1 DIQLTQSPSSLSASVGDRVTITCRASQSISIYLNWYRQQPGKAPKLLIYAASSLQSGVPS 60
|||:|||||||||||||||||||||||||| |||||:|:|||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYFCQQTYSTPPWTFGQGTKVDIK 108
||||||||| ||||||||||||||||:||| ||||||||||||||:||
Db 61 RFSGSGSGTYFTLTISSLQPEDFATYYCQQGYSTPPWTFGQGTKVEIK 108
SEQ ID NOs: 11, 13, and 15 represented in SEQ ID NO: 21 (Zhang):
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PR 22-APR-2020; 2020CN-10324347.
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CC PA (FOSU-) FOSUN KITE BIOTECHNOLOGY CO LTD.
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CC PI Zhang L, Xu M, Gao M;
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DR WPI; 2021-C1216E/092.
DR N-PSDB; BKD85852.
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CC PT New anti-B7-H3 antibody comprising e.g. heavy chain and light chain
CC PT variable regions with complementarity determining regions useful e.g. in
CC PT preparing kit, and medicine for treating diseases associated with B7-H3
CC PT expression or dysfunction.
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CC PS Claim 4; SEQ ID NO 21; 74pp; Chinese.
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Query Match 68.0%; Score 68.7; Length 108;
Best Local Similarity 25.0%;
Matches 18; Conservative 0; Mismatches 1; Indels 53; Gaps 2;
Qy 1 QSIS-----------------IYAAS---------------------------------- 9
|||| |||||
Db 27 QSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTYFTLTISSLQPEDFATY 86
Qy 10 --QQTYSTPPWT 19
|| |||||||
Db 87 YCQQGYSTPPWT 98
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
9. Claims 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (WO2021/213478, effective filing date 4/22/2020) as applied to claims 1-2, 11, and 13-20 above, and further in view of Huston, et al. (PNAS, 1988, 85:5879-5883).
The limitations of claims 1-2, 11, and 13-20 are disclosed by Zhang as discussed above including a B7H3 HCVR region amino acid sequence with identity to SEQ ID: 7 and a B7H3 LCVR amino acid sequence with identity to SEQ ID NO: 17.
Zhang does not disclose the antibody or antigen-binding fragment where the HCVR and the LCVR are linked by a linker of an amino acid sequence as set forth in SEQ ID NO: 21 or 22 and the antibody or antigen-binding fragment has an amino acid sequence set forth in SEQ ID NO: 25.
Huston teaches the use of linkers to construct Fv analogues connecting the heavy and light chain variable domains using a 15 amino acid sequence of GGGGSGGGGSGGGGS which is 100% identical to SEQ ID NO: 22. (See Huston, pg. 5879 “Protein Design”). Huston teaches that this single chain Fv design was able to produce a renatured scFV with binding specificity and affinity similar to the parent molecule. (See Huston, pg. 5879 column 1, paragraph 2).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date to use the disclosed B7H3 HCVR and LCVR regions of Zhang with the disclosed linker and teachings of Huston to produce the antibody or antigen binding fragment of SEQ ID NO: 25. It would have been obvious because the linker sequence of Huston is known in the art and Huston teaches that the linker can be used to successfully combine the HCVR and LCVR regions together for an antigen-binding fragment capable of binding similar to a full antibody. Therefore, it would have been obvious to a person of ordinary skill in the art prior to the effective filing date to combine the HCVR and LCVR regions of Zhang using the linker of Huston with a reasonable expectation of success at producing the claimed B7H3 antibody or antigen-binding fragment.
10. Claims 5-9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (WO2021/213478, effective filing date 4/22/2020) as applied to claims 1-2, 11, and 13-20 above, and further in view of Zhang 2, et al. (Molecular Therapy Oncolytics, 2020, 17:180-189).
The limitations of claim 1 are disclosed by Zhang as discussed above.
Zhang does not disclose a CAR targeting B7H3.
Zhang 2 discloses a CAR T cell targeting B7H3 comprising a signal peptide, B7H3 scFv, a hinge region, CD3ζ signaling domain, CD28 and 4-1BB costimulatory domains, and a P2A self-cleaving peptide successfully used in preclinical studies to treat cancer. (See Zhang 2 pg. 183 “Generation and Characterization of B7-H3 redirected CAR-T cells”, also Figure 4A below).
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It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date to combine the antibody of Zhang with the CAR T cell of Zhang 2 to produce the B7H3 CAR of the present claimed invention. It would have been obvious because Zhang 2 successfully created and tested a B7H3 CAR T cell for treating cancer. Therefore, it would have been obvious for a person of ordinary skill in the art prior to the effective filing date to use the antibody disclosed in Zhang with the CAR T cell of Zhang 2 with a reasonable expectation of success at creating the B7H3 CAR of the present claimed invention.
Conclusion
11. Claims 1-20 are rejected.
12. 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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/LINDSAY DUNN/Examiner, Art Unit 1642
/Laura B Goddard/Primary Examiner, Art Unit 1642
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