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 Election filed 5/9/2026, in response to the Office Action of 3/12/2026, is acknowledged and has been entered. Applicants elected without traverse Group I, including claims 1-2, 4-5, 8-13, 18, 21, and 24-26 and the species of an anti-CLDN18.2 antibody comprising a heavy chain variable region comprising a HCDR1, HCDR2, and an HCDR3 comprising the sequences of SEQ ID NOs:1, 19, and 21; and a light chain variable region comprising LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs:14, 16, and 18 from claim 13; and the species of an anti-CLDN18.2 antibody comprising a heavy chain variable region comprising a sequence of SEQ ID NO:25 and a light chain variable region comprising a sequence of SEQ ID NO:26 from claim 18. Claims 1-2, 4-5, 8-13, 18, 21, and 24-26 are pending. Claims 28, 31, 36, 39, 43, 47, and 49 have been withdrawn from further consideration by the examiner under 35 CFR 1.142(b) as being drawn to non-elected inventions.
Claims 1-2, 4-5, 8-13, 18, 21, and 24-26 are currently under prosecution as drawn to the elected species.
Priority
2. Application claims priority and benefit of PCT/CN2022/076810 filed on 2/18/2022, which claims benefit of applications PCT/CN2022/074750 filed on 1/28/2022 and PCT/CN2021/076910 filed on 2/19/2021. Applications were reviewed and determined to properly disclose the present claimed invention. Therefore, the present application is granted the benefit of PCT/CN2021/076910 and the effective filing date of 2/19/2021.
Claim Interpretation
3. The examiner’s broadest reasonable interpretation of the claim is set forth below.
Claim 18 recites:
“The antibody conjugate of claim 1 wherein: the heavy chain variable region comprises a sequence of SEQ ID NO:25 and the light chain variable region comprises a sequence of SEQ ID NO:26.”
The phrase “comprises a sequence of SEQ ID NO:25 and…comprises a sequence of SEQ ID NO:26” are reasonably interpreted as an anti-CLDN18.2 antibody conjugate comprising any sequence found in SEQ ID NO:25 and SEQ ID NO:26, 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.
4. Claims 5, 8, 18, and 25 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.
Claims 5 and 8 recites the limitation "the radionuclide" in line 2. The claims are dependent on claim 1 which recites that the radionuclide is either a therapeutic radionuclide and a diagnostic radionuclide. It is unclear which radionuclide is being characterized in either claim.
To overcome this rejection, please amend the claim to either recite the therapeutic, the diagnostic, or the therapeutic or the diagnostic radionuclide.
Claim 18 recites the limitation "the heavy chain variable region" and “the light chain variable region” in lines 3-22. Claim 18 depends from claim 1 which does not recite a heavy chain variable region or light chain variable region. There is insufficient antecedent basis for this limitation in the claim.
To overcome this rejection, amend the claim to recite “The antibody conjugate of claim 1, comprising a heavy chain variable region and a light chain variable region, wherein:”.
Claim 25 contains the trademark/trade name “nanobody”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a single domain antibody and, accordingly, the identification/description is indefinite.
To overcome this rejection, please amend claim 25 to remove “a nanobody”.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
5. Claims 8-11 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 8-9 are in improper dependent form because they depend on cancelled claims 6 and 7, respectively. For the sake of compact prosecution, examiner will interpret the claims as depending from claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
6. Claims 1-2, 4-5, 8-12, 18, 21, and 24-26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The 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 anti-CLDN18.2 antibody conjugate comprising an anti-CLDN18.2 antibody or antigen-binding fragment thereof with no structure recited in claim 1. Claim 12 identifies a partial sequence structure with a heavy chain HCDR1, HCDR2, and HCDR3 or a light chain LCDR1, LCDR2, and LCDR3 wherein the HCR1 sequence comprises SEQ ID NO:1, SEQ ID NO:13 or a sequence with at least 80% sequence identity, the HCR2 sequence comprises the sequence SEQ ID NO:32 or SEQ ID NO:15 or a sequence of at least 80% identity, the HCDR3 sequence comprising the sequence SEQ ID NO:33 or SEQ ID NO:17 or a sequence of at least 80% identity; the LCDR1 sequence comprises the sequence of SEQ ID NO:34 or a sequence of at least 80% identity, the LCDR2 sequence comprises the sequence of SEQ ID NO:35 or a sequence of at least 80% identity, and the LCDR3 sequence comprises the sequence of SEQ ID NO:36 or a sequence of at least 80% identity. Claim 18 further identifies a partial structure of the anti-CLDN18.2 antibody conjugate by the heavy chain variable region comprises a sequence of SEQ ID NO:25, as few as two consecutive amino acids long; and the light chain variable region comprises a sequence of SEQ ID NO:26, as few as two consecutive amino acids long.
Thus, the claims identify the antibody by the function of binding CLDN18.2 and partial amino acid sequence structures of at least 80% identity to the HCDR1 of the sequences of SEQ ID NOs:1 or 13, HCDR2 of the sequences of SEQ ID NOs:32 or 15, HCDR3 of the sequences of SEQ ID NOs:33 or 17; or at least 80% identity to the LCDR1 of the sequence of SEQ ID NO:34, the LCDR2 of the sequence of SEQ ID NO:35, and the LCDR3 sequence of SEQ ID NO:36; or the partial structures of the heavy chain variable region comprising a sequence of SEQ ID NO:25, as few as two amino acids long, and the light chain variable region comprising a sequence of SEQ ID NO:26, as few as two amino acids long. Thus, the claims encompass a vast genus of antibody variants comprising variable HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3, heavy chain variable and light chain variable regions required to bind CLDN18.2.
The instant specification discloses seven different anti-CLDN18.2 antibodies with specific site mutations that bind to CLDN18.2 expressed on transfected HEK293 cells.
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The instant specification further identified 6 different structurally distinct species of antibody 18B10 that comprise 3 specific heavy chains, 3 specific light chains and 6 different combinations of heavy and light chain combinations that can produce anti-CLDN18.2 antibodies. (Example 7).
The instant specification further identified species of distinct structural mutated 18B10 antibodies able to bind CLDN18.2.
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Thus, the instant specification discloses making six different structurally distinct antibodies and 50 different structurally distinct mutations that can be made and retain the binding function to CLDN18.2. The specification fails to disclose any other HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, or LCDR3 sequence variants comprising 80% of amino acid sequences needed for SEQ ID NOs:1, 13, 32, 15, 33, 17, 34, 35, and 36 that possess the function of binding CLDN18.2. The specification also fails to disclose any other heavy chain regions or light chain region sequence variants having as few as two consecutive amino acid sequences found in SEQ ID NOs:25 and 26 that possess the function of binding CLDN18.2.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative antibody variants that function to bind CLDN18.2, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.).
In this case, the only factor present in the claims is a recitation of the antibody function, “anti-CLDN18.2”, and partial sequence structure as stated above. The instant specification fails to describe structural features common to the members of the antibody genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose representative antibody variant sequences that function as claimed. 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 the 6 structurally distinct antibodies and the mutations disclosed in the tables shown above, the specification fails to provide the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3, heavy chain region and light chain region structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of antibody sequence variants for the genus of antibodies 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.
The claims broadly encompass any sequence variant having at least 80% identity to the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 SEQ ID NOs:1, 13, 32, 15, 33, 17, 34, 35, and 36 that functions to bind CLDN18.2; or as few as two consecutive amino acid sequences from heavy chain variable region and light chain variable region of SEQ ID NOs:25 and 26 that function bind CLDN18.2. Applicants have not established any reasonable structure-function correlation with regards to the sequences in the CDRs or heavy or light chain variable regions that can be altered and still maintain CLDN18.2 binding function Given the well-known high level of polymorphism of antibody CDR sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of antibodies encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a single parental anti-CLDN18.2 antibody comprising at least 80% identity to SEQ ID NOs:1, 13, 32, 15, 33, 17, 34, 35, and 36 or the amino acid structure of SEQ ID NOs: 25 and 26 to the structure of any variants required to bind CLDN18.2 as broadly claimed. Therefore, one could not readily envision members of the broadly claimed genus.
Although Applicants may argue that it is possible to screen for antibodies that bind CLDN18.2 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 yet to be discovered that may function as claimed. The CLDN18.2 antigen provides no information about the structure of an antibody that binds to it.
Given the lack of representative examples to support the full scope of the claimed variant antibodies, and lack of reasonable structure-function correlation with regards to the unknown variable sequences in the CDRs or variable chain regions that provide CLDN18.2-binding function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibody variants that bind CLDN18.2 and comprise at least 80% identity to SEQ ID NOs:1, 13, 32, 15, 33, 17, 34, 35, and 36 or comprise as few as two defined consecutive amino acids in SEQ ID NOs:25 and 26 that is required to practice the claimed invention.
Examiner Suggestion: To overcome the rejection, examiner suggests:
Amend claim 1 to recite and require the anti-CLDN18.2 comprise at least the six defined CDR SEQ ID NOs from the heavy and light chain variable domains (where each amino acid in the CDR sequences is defined).
Amend claim 12 to delete the phrases “or a homologue sequence of at least 80% sequence identity thereof”.
Amend claim 18 to recite the antibody of claim 1 comprises a heavy chain variable region and a light chain variable region, and to change the language from “comprising a sequence of SEQ ID NO” to “comprising the sequence of SEQ ID NO”.
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.
7. Claims 1-2, 5, 8-10, 12-13, 18, 21, 24-26 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Qian (US2022/0306765 A1, effective filing date 8/20/2019) and as evidenced by De Leon Rodriguez (Bioconjugate Chem, 2008, 19(2):391-402).
Qian discloses an anti-CLDN18.2 antibody that can be conjugated to a radioactive isotope. (See Qian pg. 27 [0398]). The conjugated isotope could be for diagnostic imaging and use 123I, 124I, 125I, 131I, 111In, 64Cu, 67Cu, 86Y, 90Y, 177Lu, 211At, 186Re, 153Sm, 212Bi, and 32P, (See Qian pg. 27 [0400]) and also for therapeutic purposes using 211At, 131I, 125I, 90Y, 186Re, 153Sm, 212Bi, 32P, and 212Pb (See Qian pg. 28 [0409]). The anti-CLDN18.2 antibody can be conjugated to the radioactive isotopes through a chelator, including DOTA, DTPA, and TETA. (See Qian pg. 28 [0409]). As evidenced by De Leon Rodriguez, DOTA contains eight chelation atoms, four of nitrogen and 4 of oxygen. (See De Leon Rodriguez, pg. 395 column 1, ‘Coordination Chemistry’).
Qian further discloses the anti-CLDN18.2 antibody comprising a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises heavy chain HCDR1, HCDR2 and HCDR3 sequences and the light chain variable region comprises light chain LCDR1, LCDR2 and LCDR3 sequences, wherein: the HCDR1 sequence comprises GYNMN (SEQ ID NO: 1), or TYFIGVG (SEQ ID NO: 13), or a homologue sequence of at least 80% sequence identity thereof; the HCDR2 sequence comprises X1IDPYYX2X3TX4YNQKFX5G (SEQ ID NO:32), or HIWWNDNKYYNTALKS (SEQ ID NO: 15; the HCDR3 sequence comprises X6X7X8GNAFDY (SEQ ID NO: 33), or MGSGAWFTY (SEQ ID NO: 17); the LCDR1 sequence comprises KSSQX9LX10NX11GNX12KNYLT (SEQ ID NO: 34); the LCDR2 sequence comprises WASTRX13S (SEQ ID NO: 35); the LCDR3 sequence comprises QNDYX14X15PX16T (SEQ ID NO: 36); wherein X1 is N or Y or H, X2 is G or V, X3 is A or G or T, X4 is R or T or S, X5 is K or R, X6 is S or M, X7 is or F, X8 is Y or H, X9 is S or N, X10 is L or F, X11 is S or N, X12 is Q or L, X13 is E or K, X14 is S or Y, X15 is F or Y and X16 is F or L. Qian further discloses the anti-CLDN18.2 antibody comprises the HCDR1 comprises the sequence of SEQ ID NO: 1 (SEQ ID NO:1), the HCDR2 comprises the sequence of SEQ ID NO: 19 (SEQ ID NO:19), the HCDR3 comprises the sequence of SEQ ID NO: 21 (SEQ ID NO:19); the LCDR1 comprises the sequence of SEQ ID NO: 14 (SEQ ID NO:14), the LCDR2 comprises the sequence of SEQ ID NO: 16 (SEQ ID NO:16), and the LCDR3 comprises the sequence of SEQ ID NO: 18 (SEQ ID NO:18). (See Qian claims 16-20, also see alignments below).
Qian further discloses the heavy chain variable region comprises a sequence selected from the group consisting of SEQ ID NO: 25; and wherein the light chain variable region comprises a sequence selected from the group consisting of SEQ ID NO: 26, which match the present applications SEQ ID NO:25 and 26. (See Qian, claims 23-25, also alignments below).
Qian further discloses the constant region is a human IgG. (See Qian, claim 29). The antibody is humanized (claim 35), can be in a pharmaceutical composition (claim 51), and can be in the form of a diabody, a Fab, a Fab', a F(ab')2, a Fd, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a bispecific dsFv (dsFv-dsFv'), a disulfide stabilized diabody (ds diabody), a single-chain antibody molecule (scFv), an scFv dimer (bivalent diabody), or a multi-specific antibody (claim 37).
SEQ ID NO:1 is 100% identical to SEQ ID NO:1 (Qian):
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SEQ ID NO:19 is 100% identical to SEQ ID NO:19 (Qian):
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SEQ ID NO:21 is 100% identical to SEQ ID NO:21 (Qian):
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SEQ ID NO:25 is 100% identical to SEQ ID NO:25 (Qian):
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SEQ ID NO:14 is 100% identical to SEQ ID NO:14 (Qian):
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SEQ ID NO:16 is 100% identical to SEQ ID NO:16 (Qian):
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SEQ ID NO:18 is 100% identical to SEQ ID NO:18 (Qian):
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SEQ ID NO:26 is 100% identical to SEQ ID NO:26 (Qian):
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8. Claims 1, 18, 24-26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang (CA3138414 A1, pub. 11/19/2020).
Yang discloses an anti-CLDN18.2 antibody that can be conjugated to a radionuclide for detection purposes (See Yang, pg. 6 lines 30-33, also claim 15).
Regarding claim 18, Yang further discloses an anti-CLDN18.2 antibody of the antibody conjugate comprising the heavy chain variable region comprises a sequence of SEQ ID NO:25 and the light chain variable region comprises a sequence of SEQ ID NO:26. (SEQ ID NOs:120, 121, see alignment below).
In regard to claims 24-26, Yang discloses the anti-CLDN18.2 antibody or antigen-binding fragment can be a humanized antibody or antigen-binding fragment in the form of Fab, Fv, scFv, F(ab’)2, and a single domain antibody. (See Yang pg. 6). Yang also discloses the anti-CLDN18.2 antibody conjugate can be included in a pharmaceutical composition with a pharmaceutically acceptable carrier. (See Yang pgs. 7-8).
SEQ ID NO:25 matches SEQ ID NO:120 (Yang):
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SEQ ID NO:26 matches SEQ ID NO:121 (Yang):
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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 2, 4-5, and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Yang (CA3138414 A1, pub. 11/19/2020) in further view of Viola-Villegas (WO2019/040740 A1, pub. 2/28/2019) and Farr (Mol Pharm, 2/1/2021 18(2):593-609).
Yang discloses the limitations of claim 1 as discussed above.
Yang does not disclose specific radionuclides used in the antibody conjugate or that the radionuclides are conjugated through a chelator. Yang does not disclose the antibody conjugate being used with a diagnostic radionuclide for detection in PET or SPECT imaging.
Viola-Villegas teaches that an antibody for a specific target can be conjugated to the radionuclide through a chelator. (See Viola-Villegas, pg. 2 [0007]). Viola-Villegas further teaches the radionuclide can be for diagnostic purposes and used with PET and SPECT imaging and include: 18F, 45Ti, 64Cu, 68Ga, 86Y, 89Zr, and 124I. (See Viola-Villegas pgs. 13-14 [0071]). Viola-Villegas further teaches that therapeutic radionuclides can include: 125I, 131I, 177Lu, 186Re, and 225Ac. (See Viola-Villegas pg. 14 [0072]). Viola-Villegas also teaches a chelator attached to an antibody where the radionuclide is 89Zr and the chelator is DFO. (See Viola-Villegas, pg. 19[00102]). Viola-Villegas teaches the chemical structure of DFO as comprising oxygen shown below.
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Viola-Villegas does not teach DFO as comprising 3 or more atoms for chelation.
Farr et al. (Mol. Pharm. 2/1/2021, 18(2):593-609) teaches DFO is naturally an iron chelator containing six Oxygen atoms for chelation. (See Farr, abstract).
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 anti-CLDN18.2 antibody conjugate of Yang with the teachings of Viola-Villegas and Farr for the present claimed invention. It would have been obvious because Viola-Villegas teaches the conjugation method of using chelators for conjugating a monoclonal antibody to a radionuclide that is similar to the monoclonal antibody disclosed in Yang. It would have been obvious because Viola-Villegas teaches that the conjugation method of using a chelator is versatile and could be used for conjugating a radionuclide for both therapeutic and diagnostic purposes. Therefore, it would have been obvious for a person of ordinary skill in the art prior to the effective filing date to combine the teachings of Viola-Villegas with the anti-CLDN18.2 antibody conjugate disclosed in Yang to produce the present claimed invention with a reasonable expectation of success.
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.
10. Claims 1-2, 4-5, 8-13, 18, 21, and 24-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16, 23, 25, 29, 35, 37, 46, and 51 of copending Application No. 17636373 in view of Viola-Villegas (WO2019/040740 A1, pub. 2/28/2019) and Farr (Mol Pharm, 2/1/2021 18(2):593-609).
The co-pending application discloses an anti-CLDN18.2 antibody or antigen binding fragment comprising a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises heavy chain HCDR1, HCDR2 and HCDR3 sequences and the light chain variable region comprises light chain LCDR1, LCDR2 and LCDR3 sequences, wherein:
the HCDR1 sequence comprises GYNMN (SEQ ID NO: 1), or TYFIGVG (SEQ ID NO: 13), or a homologue sequence of at least 80% sequence identity thereof; the HCDR2 sequence comprises X1IDPYYX2X3TX4YNQKFX5G (SEQ ID NO:32), or HIWWNDNKYYNTALKS (SEQ ID NO: 15; the HCDR3 sequence comprises X6X7X8GNAFDY (SEQ ID NO: 33), or MGSGAWFTY (SEQ ID NO: 17); the LCDR1 sequence comprises KSSQX9LX10NX11GNX12KNYLT (SEQ ID NO: 34); the LCDR2 sequence comprises WASTRX13S (SEQ ID NO: 35); the LCDR3 sequence comprises QNDYX14X15PX16T (SEQ ID NO: 36); wherein X1 is N or Y or H, X2 is G or V, X3 is A or G or T, X4 is R or T or S, X5 is K or R, X6 is S or M, X7 is or F, X8 is Y or H, X9 is S or N, X10 is L or F, X11 is S or N, X12 is Q or L, X13 is E or K, X14 is S or Y, X15 is F or Y and X16 is F or L; and wherein:
the HCDR1 comprises the sequence of SEQ ID NO: 1, the HCDR2 comprises the sequence of SEQ ID NO: 19, the HCDR3 comprises the sequence of SEQ ID NO: 21; the LCDR1 comprises the sequence of SEQ ID NO: 14, the LCDR2 comprises the sequence of SEQ ID NO: 16, and the LCDR3 comprises the sequence of SEQ ID NO: 18.
The co-pending application further discloses the heavy chain variable region comprises a sequence selected from the group consisting of SEQ ID NO: 25; and wherein the light chain variable region comprises a sequence selected from the group consisting of SEQ ID NO: 26.
The present application SEQ ID NOs:1, 19, and 21 and SEQ ID NO:25 match 100% the co-pending application SEQ ID NOs:1, 19, 21, and 25, see alignments below. The present application SEQ ID NOs:14, 16, and 18 and SEQ ID NO:26 match 100% of the co-pending applications SEQ ID NO:14, 16, 18, and 26, see alignments below.
The co-pending application further discloses the constant region is a human IgG. The antibody is humanized, can be conjugated to a radionuclide, can be in a pharmaceutical composition, and can be in the form of a diabody, a Fab, a Fab', a F(ab')2, a Fd, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a bispecific dsFv (dsFv-dsFv'), a disulfide stabilized diabody (ds diabody), a single-chain antibody molecule (scFv), an scFv dimer (bivalent diabody), or a multi-specific antibody.
The co-pending application does not disclose specific radionuclides used in the antibody conjugate or that the radionuclides are conjugated through a chelator. The co-pending application does not disclose the antibody conjugate being used with a diagnostic radionuclide for detection in PET or SPECT imaging.
Viola-Villegas teaches that an antibody for a specific target can be conjugated to the radionuclide through a chelator. (See Viola-Villegas, pg. 2 [0007]). Viola-Villegas further teaches the radionuclide can be for diagnostic purposes and used with PET and SPECT imaging and include: 18F, 45Ti, 64Cu, 68Ga, 86Y, 89Zr, and 124I. (See Viola-Villegas pgs. 13-14 [0071]). Viola-Villegas further teaches that therapeutic radionuclides can include: 125I, 131I, 177Lu, 186Re, and 225Ac. (See Viola-Villegas pg. 14 [0072]). Viola-Villegas also teaches a chelator attached to an antibody where the radionuclide is 89Zr and the chelator is DFO. (See Viola-Villegas, pg. 19[00102]). Viola-Villegas teaches the chemical structure of DFO as comprising oxygen shown below.
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185
323
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Viola-Villegas does not teach DFO as comprising 3 or more atoms for chelation.
Farr et al. (Mol. Pharm. 2/1/2021, 18(2):593-609) teaches DFO is naturally an iron chelator containing six atoms for chelation and comprise Oxygen atoms. (See Farr, abstract).
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 anti-CLDN18.2 antibody claimed in the co-pending application with the teachings of Viola-Villegas and Farr to produce the present claimed antibody conjugate. It would have been obvious because the co-pending application claims the antibody being able to be conjugated to a radioactive isotope and Viola-Villegas teaches conjugation of a monoclonal antibody to a radionuclide for therapeutic and diagnostic purposes. Therefore, it would have been obvious to apply the teaching of Viola-Villegas and Farr to the anti-CLDN18.2 antibody claimed in the co-pending application with a reasonable expectation of success at producing the claimed antibody conjugate of the present application.
This is a provisional nonstatutory double patenting rejection.
SEQ ID NO:1 is 100% identical to SEQ ID NO:1 (Co-pending app# 17636373)
PNG
media_image4.png
389
674
media_image4.png
Greyscale
SEQ ID NO:19 is 100% identical to SEQ ID NO:19 (Co-pending app# 17636373)
PNG
media_image5.png
388
649
media_image5.png
Greyscale
SEQ ID NO:21 is 100% identical to SEQ ID NO:21 (Co-pending app# 17636373)
PNG
media_image6.png
398
672
media_image6.png
Greyscale
SEQ ID NO:25 is 100% identical to SEQ ID NO:25 (Co-pending app# 17636373)
PNG
media_image7.png
462
671
media_image7.png
Greyscale
SEQ ID NO:14 is 100% identical to SEQ ID NO:14 (Co-pending app# 17636373)
PNG
media_image8.png
381
671
media_image8.png
Greyscale
SEQ ID NO:16 is 100% identical to SEQ ID NO:16 (Co-pending app# 17636373)
PNG
media_image9.png
387
652
media_image9.png
Greyscale
SEQ ID NO:18 is 100% identical to SEQ ID NO:18 (Co-pending app# 17636373)
PNG
media_image10.png
377
678
media_image10.png
Greyscale
SEQ ID NO:26 is 100% identical to SEQ ID NO:26 (Co-pending app# 17636373)
PNG
media_image11.png
459
664
media_image11.png
Greyscale
11. Claims 1-2, 4-5, 8-13, 18, 21, and 24-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32, 33, and 43 of copending Application No. 18710628 in view of Yang (CA3138414 A1, pub. 11/19/2020) in further view of Viola-Villegas (WO2019/040740 A1, pub. 2/28/2019) Farr (Mol Pharm, 2/1/2021 18(2):593-609).
The co-pending application claims an anti-CLDN18.2 antibody comprising heavy chain HCDR1, HCDR2 and HCDR3 and/or light chain LCDR1, LCDR2 and LCDR3 sequences, wherein: the HCDR1 sequence comprises GYNMN (SEQ ID NO: 1); the HCDR2 sequence comprises NIDPYYGGTSYNQKFKG (SEQ ID NO: 2); the HCDR3 sequence comprises MYHGNAFDY (SEQ ID NO: 3); the LCDR1 sequence comprises KSSQSLLNSGNLKNYLT (SEQ ID NO: 4); the LCDR2 sequence comprises WASTRKS (SEQ ID NO: 5); the LCDR3 sequence comprises QNDYSYPLT (SEQ ID NO: 6), where SEQ ID NOs:2, 3, 4, 5, and 6 are variants of the present applications SEQ ID NOs:32, 33, 34, 35, and 36, respectively, see alignments below. The co-pending application further claims the heavy chain variable region comprising SEQ ID NO:12 and a light chain variable region comprising SEQ ID NO:15, which are 100% identical to the present applications SEQ ID NO:25 and 26, respectively, see alignments below.
The co-pending application does not claim the anti-CLDN18.2 antibody as comprising a constant region of a human IgG antibody, as being humanized, as being the form of a number of different antigen-binding fragments, or as a part of a pharmaceutical composition. The co-pending application did not disclose the anti-CLDN18.2 antibody as being conjugated to a radionuclide through a chelator.
Yang discloses an anti-CLDN18.2 antibody conjugate as claimed in claims 1 as discussed above. Yang further discloses the antibody comprises a constant region of human IgG. (See Yang, pg. 35 line 8).
Yang does not disclose specific radionuclides used in the antibody conjugate or that the radionuclides are conjugated through a chelator. Yang does not disclose the antibody conjugate being used with a diagnostic radionuclide for detection in PET or SPECT testing.
Viola-Villegas teaches that an antibody for a specific target can be conjugated to the radionuclide through a chelator. (See Viola-Villegas, pg. 2 [0007]). Viola-Villegas further teaches the radionuclide can be for diagnostic purposes and used with PET and SPECT imaging and include: 18F, 45Ti, 64Cu, 68Ga, 86Y, 89Zr, and 124I. (See Viola-Villegas pgs. 13-14 [0071]). Viola-Villegas further teaches that therapeutic radionuclides can include: 125I, 131I, 177Lu, 186Re, and 225Ac. (See Viola-Villegas pg. 14 [0072]). Viola-Villegas also teaches a chelator attached to an antibody where the radionuclide is 89Zr and the chelator is DFO. (See Viola-Villegas, pg. 19[00102]). Viola-Villegas teaches the chemical structure of DFO as comprising oxygen shown below.
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185
323
media_image14.png
Greyscale
Viola-Villegas does not teach DFO as comprising 3 or more atoms for chelation.
Farr et al. (Mol. Pharm. 2/1/2021, 18(2):593-609) teaches DFO is naturally an iron chelator containing six atoms for chelation and comprise Oxygen atoms. (See Farr, abstract).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective date to use the antibody of the co-pending application with the teachings of Yang, Viola-Villegas, and Farr to produce the present claimed invention. It would have been obvious because Yang teaches that antibodies like the one in the co-pending application can be conjugated to a radionuclide and Viola-Villegas teaches a monoclonal antibody being conjugated to a radionuclide by a chelator for therapeutic and diagnostic purposes as disclosed in the present claimed invention. Therefore, it would have been obvious to use the antibody claimed in the co-pending application with the teachings of Yang, Viola-Villegas, and Farr to produce an anti-CLDN antibody conjugate for use with therapeutic and diagnostic radionuclides as claimed in the present invention with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Co-Pending App #18710628
Present Application
SEQ ID NO:2 NIDPYYGGTSYNQKFKG
SEQ ID NO:32 [N/Y]IDPYY[G/V][A/G/T]T[R/T/S]YNQKF[K/R]G
SEQ ID NO:3 MYHGNAFDY
SEQ ID NO:33 [S/M][Y/F][Y/H]GNAFDY
SEQ ID NO:4 KSSQSLLNSGNLKNYLT
SEQ ID NO:34 KSSQ[S/N]L[L/F]N[S/N]GN[Q/L]KNYLT
SEQ ID NO:5 WASTRKS
SEQ ID NO:35 WASTR[E/K]S
SEQ ID NO:6 QNDYSYPLT
SEQ ID NO:36 QNDY[S/Y][F/Y]P[F/L]T
SEQ ID NO:12 (Co-pending app# 18710628) is 100% SEQ ID NO:25
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 634 100.0 118 US-17-636-373-25 2022-02-18 3 NOVEL ANTI- CLDN18.2 ANTIBODIES
ALIGNMENT:
Query Match 100.0%; Score 634; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYNMNWVRQAPGQGLEWMGNIDPYYGGTSY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYNMNWVRQAPGQGLEWMGNIDPYYGGTSY 60
Qy 61 NQKFKGRVTMTIDKSTSTVYMELSSLRSEDTAVYYCARMYHGNAFDYWGQGTTVTVSS 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFKGRVTMTIDKSTSTVYMELSSLRSEDTAVYYCARMYHGNAFDYWGQGTTVTVSS 118
US-18-710-628-12
Filing date in PALM: 2024-05-16
Sequence 12, US/18710628
Publication No. US20250326834A1
GENERAL INFORMATION
APPLICANT: SUZHOU TRANSCENTA THERAPEUTICS CO., LTD. (en)
TITLE OF INVENTION: COMBINATION THERAPY OF CLAUDIN 18.2 ANTAGONIST AND PD-1/PD-L1 AXIS INHIBITOR (en)
FILE REFERENCE: 063694-8011US01
CURRENT APPLICATION NUMBER: US/18/710,628
CURRENT FILING DATE: 2024-05-16
NUMBER OF SEQ ID NOS: 64
SEQ ID NO 12
LENGTH: 118
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..118
QUALIFIERS: mol_type = protein
organism = synthetic construct
SEQ ID NO:15 (Co-pending app# 18710628) is 100% SEQ ID NO:26
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 593 100.0 113 US-17-636-373-26 2022-02-18 3 NOVEL ANTI- CLDN18.2 ANTIBODIES
ALIGNMENT:
Query Match 100.0%; Score 593; Length 113;
Best Local Similarity 100.0%;
Matches 113; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNLKNYLTWYQQKPGQPPKLLIYWASTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNLKNYLTWYQQKPGQPPKLLIYWASTR 60
Qy 61 KSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPLTFGGGTKVEIK 113
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPLTFGGGTKVEIK 113
US-18-710-628-15
Filing date in PALM: 2024-05-16
Sequence 15, US/18710628
Publication No. US20250326834A1
GENERAL INFORMATION
APPLICANT: SUZHOU TRANSCENTA THERAPEUTICS CO., LTD. (en)
TITLE OF INVENTION: COMBINATION THERAPY OF CLAUDIN 18.2 ANTAGONIST AND PD-1/PD-L1 AXIS INHIBITOR (en)
FILE REFERENCE: 063694-8011US01
CURRENT APPLICATION NUMBER: US/18/710,628
CURRENT FILING DATE: 2024-05-16
NUMBER OF SEQ ID NOS: 64
SEQ ID NO 15
LENGTH: 113
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..113
QUALIFIERS: mol_type = protein
organism = synthetic construct
12. Claims 1-2, 4-5, 8-13, 18, 21, 24-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of copending Application No. 18879798 in view of in view of Qian (US2022/0306765 A1, effective filing date 8/20/2019), Viola-Villegas (WO2019/040740 A1, pub. 2/28/2019) and De Leon Rodriguez (Bioconjugate Chem, 2008, 19(2):391-402).
The co-pending application claims a pharmaceutical composition including an anti-CLDN18.2 antibody comprising a CDR1, CDR2, and a CDR3 of the heavy chain variable region as set forth in SEQ ID NO:7 and a CDR1, CDR2, and a CDR3 of the light chain variable region as set forth in SEQ ID NO:8.
The co-pending application does not claim an anti-CLDN18.2 antibody conjugated to a radionuclide for therapeutic and diagnostic purposes, where the conjugation occurs through a chelator. The anti-CLDN18.2 antibody is further not claimed using the CDR amino acid sequence variants of claim 12 in the present application or that the antibody is humanized and comprises a constant region of a human IgG and is various antigen-binding fragments.
Qian discloses an anti-CLDN18.2 antibody that can be conjugated to a radioactive isotope. (See Qian pg. 27 [0398]). The conjugated isotope could be for diagnostic imaging and use 123I, 124I, 125I, 131I, 111In, 64Cu, 67Cu, 86Y, 90Y, 177Lu, 211At, 186Re, 153Sm, 212Bi, and 32P, (See Qian pg. 27 [0400]) and also for therapeutic purposes using 211At, 131I, 125I, 90Y, 186Re, 153Sm, 212Bi, 32P, and 212Pb (See Qian pg. 28 [0409]). The anti-CLDN18.2 antibody can be conjugated to the radioactive isotopes through a chelator, including DOTA, DTPA, and TETA. (See Qian pg. 28 [0409]). As evidenced by De Leon Rodriguez, DOTA contains eight chelation atoms, four of nitrogen and 4 of oxygen. (See De Leon Rodriguez, pg. 395 column 1, ‘Coordination Chemistry’).
Qian further discloses the anti-CLDN18.2 antibody comprising a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises heavy chain HCDR1, HCDR2 and HCDR3 sequences and the light chain variable region comprises light chain LCDR1, LCDR2 and LCDR3 sequences, wherein: the HCDR1 sequence comprises GYNMN (SEQ ID NO: 1), or TYFIGVG (SEQ ID NO: 13), or a homologue sequence of at least 80% sequence identity thereof; the HCDR2 sequence comprises X1IDPYYX2X3TX4YNQKFX5G (SEQ ID NO:32), or HIWWNDNKYYNTALKS (SEQ ID NO: 15; the HCDR3 sequence comprises X6X7X8GNAFDY (SEQ ID NO: 33), or MGSGAWFTY (SEQ ID NO: 17); the LCDR1 sequence comprises KSSQX9LX10NX11GNX12KNYLT (SEQ ID NO: 34); the LCDR2 sequence comprises WASTRX13S (SEQ ID NO: 35); the LCDR3 sequence comprises QNDYX14X15PX16T (SEQ ID NO: 36); wherein X1 is N or Y or H, X2 is G or V, X3 is A or G or T, X4 is R or T or S, X5 is K or R, X6 is S or M, X7 is or F, X8 is Y or H, X9 is S or N, X10 is L or F, X11 is S or N, X12 is Q or L, X13 is E or K, X14 is S or Y, X15 is F or Y and X16 is F or L. (See Qian claims 16-20).
Qian further discloses the constant region is a human IgG. (See Qian, claim 29). The antibody is humanized (claim 35) and can be in the form of a diabody, a Fab, a Fab', a F(ab')2, a Fd, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a bispecific dsFv (dsFv-dsFv'), a disulfide stabilized diabody (ds diabody), a single-chain antibody molecule (scFv), an scFv dimer (bivalent diabody), or a multi-specific antibody (claim 37).
Qian does not disclose the antibody conjugate can be used with PET and SPECT imaging and where the radionuclide is 89Zr and the chelator is DFO.
Viola-Villegas teaches the radionuclide can be for diagnostic purposes and used with PET and SPECT imaging. (See Viola-Villegas pgs. 13-14 [0071]). Viola-Villegas also teaches a chelator attached to an antibody where the radionuclide is 89Zr and the chelator is DFO. (See Viola-Villegas, pg. 19[00102]).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date to use the antibody of the co-pending application with the teachings of Qian and Viola-Villegas to produce the present claimed invention. It would have been obvious because the co-pending application claims an anti-CLDN18.2 antibody and Qian teaches conjugating an anti-CLDN18.2 antibody to radionuclides for therapeutic and diagnostic purposes as disclosed in the present claimed invention. Further, Viola-Villegas expands on the teachings of Qian to teach a specific radionuclide and chelator combination for use in therapeutic or diagnostic purposes. Therefore, it would have been obvious to a person of ordinary skill prior to the effective filing date to use the antibody claimed in the co-pending application with the teachings of Qian and Viola-Villegas to produce an anti-CLDN18.2 antibody conjugate for use with therapeutic and diagnostic radionuclides as claimed in the present application with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
SEQ ID NOs:1, 19, and 21 are 100% matched to SEQ ID NO:7 (18/879,798):
US-18-879-798-7
Sequence 7, US/18879798
GENERAL INFORMATION
APPLICANT: SUZHOU TRANSCENTA THERAPEUTICS CO., LTD.; TRANSCENTA HOLDING LIMITED; TRANSCENTA THERAPEUTICS, INC. (en)
TITLE OF INVENTION: STABLE PHARMACEUTICAL FORMULATION COMPRISING AN ANTI-CLDN18.2 ANTIBODY (en)
FILE REFERENCE: 063694-8012WO01
CURRENT APPLICATION NUMBER: US/18/879,798
CURRENT FILING DATE: 2024-12-29
NUMBER OF SEQ ID NOS: 10
SEQ ID NO 7
LENGTH: 118
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..118
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 86.6%; Score 158.4; Length 118;
Best Local Similarity 40.3%;
Matches 31; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 GYNMN--------------NIDPYYGGTSYNQKFKG------------------------ 22
||||| |||||||||||||||||
Db 31 GYNMNWVRQAPGQGLEWMGNIDPYYGGTSYNQKFKGRVTMTIDKSTSTVYMELSSLRSED 90
Qy 23 --------MYHGNAFDY 31
|||||||||
Db 91 TAVYYCARMYHGNAFDY 107
SEQ ID NOs:14, 16, and 18 are 100% matched to SEQ ID NO:7 (18/879,798):
US-18-879-798-8
Sequence 8, US/18879798
GENERAL INFORMATION
APPLICANT: SUZHOU TRANSCENTA THERAPEUTICS CO., LTD.; TRANSCENTA HOLDING LIMITED; TRANSCENTA THERAPEUTICS, INC. (en)
TITLE OF INVENTION: STABLE PHARMACEUTICAL FORMULATION COMPRISING AN ANTI-CLDN18.2 ANTIBODY (en)
FILE REFERENCE: 063694-8012WO01
CURRENT APPLICATION NUMBER: US/18/879,798
CURRENT FILING DATE: 2024-12-29
NUMBER OF SEQ ID NOS: 10
SEQ ID NO 8
LENGTH: 113
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..113
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 85.6%; Score 147.3; Length 113;
Best Local Similarity 41.2%;
Matches 33; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KSSQSLLNSGNLKNYLT---------------WASTRKS--------------------- 24
||||||||||||||||| |||||||
Db 24 KSSQSLLNSGNLKNYLTWYQQKPGQPPKLLIYWASTRKSGVPDRFSGSGSGTDFTLTISS 83
Qy 25 -----------QNDYSYPLT 33
|||||||||
Db 84 LQAEDVAVYYCQNDYSYPLT 103
SEQ ID NO:25 are 100% identical to SEQ ID NO:7 (18/879,798):
US-18-879-798-7
Sequence 7, US/18879798
GENERAL INFORMATION
APPLICANT: SUZHOU TRANSCENTA THERAPEUTICS CO., LTD.; TRANSCENTA HOLDING LIMITED; TRANSCENTA THERAPEUTICS, INC. (en)
TITLE OF INVENTION: STABLE PHARMACEUTICAL FORMULATION COMPRISING AN ANTI-CLDN18.2 ANTIBODY (en)
FILE REFERENCE: 063694-8012WO01
CURRENT APPLICATION NUMBER: US/18/879,798
CURRENT FILING DATE: 2024-12-29
NUMBER OF SEQ ID NOS: 10
SEQ ID NO 7
LENGTH: 118
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..118
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 100.0%; Score 634; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYNMNWVRQAPGQGLEWMGNIDPYYGGTSY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYNMNWVRQAPGQGLEWMGNIDPYYGGTSY 60
Qy 61 NQKFKGRVTMTIDKSTSTVYMELSSLRSEDTAVYYCARMYHGNAFDYWGQGTTVTVSS 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFKGRVTMTIDKSTSTVYMELSSLRSEDTAVYYCARMYHGNAFDYWGQGTTVTVSS 118
SEQ ID NO:26 are 100% matched to SEQ ID NO:8 (18/879,798):
US-18-879-798-8
Sequence 8, US/18879798
GENERAL INFORMATION
APPLICANT: SUZHOU TRANSCENTA THERAPEUTICS CO., LTD.; TRANSCENTA HOLDING LIMITED; TRANSCENTA THERAPEUTICS, INC. (en)
TITLE OF INVENTION: STABLE PHARMACEUTICAL FORMULATION COMPRISING AN ANTI-CLDN18.2 ANTIBODY (en)
FILE REFERENCE: 063694-8012WO01
CURRENT APPLICATION NUMBER: US/18/879,798
CURRENT FILING DATE: 2024-12-29
NUMBER OF SEQ ID NOS: 10
SEQ ID NO 8
LENGTH: 113
TYPE: PRT
FEATURE:
NAME/KEY: source
LOCATION: 1..113
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 100.0%; Score 593; Length 113;
Best Local Similarity 100.0%;
Matches 113; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNLKNYLTWYQQKPGQPPKLLIYWASTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNLKNYLTWYQQKPGQPPKLLIYWASTR 60
Qy 61 KSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPLTFGGGTKVEIK 113
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPLTFGGGTKVEIK 113
12. Claims 1-2, 4-5, 8-13, 18, 21, and 24-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 36-38, 45-46, 48-49 of copending Application No. 19489267 in view of Qian (US2022/0306765 A1, effective filing date 8/20/2019), Viola-Villegas (WO2019/040740 A1, pub. 2/28/2019) and De Leon Rodriguez (Bioconjugate Chem, 2008, 19(2):391-402).
The co-pending application claims an anti-CLDN18.2 antagonist that is linked to a conjugate including a radioactive isotope. The anti-CLDN18.2 antibody is further claimed as comprising the antigen binding domain comprising HCDR1, HCDR2 and HCDR3 and/or LCDR1, LCDR2 and LCDR3 sequences, wherein: the HCDR1 sequence comprises GYNMN (SEQ ID NO: 1), or a homologue sequence of at least 80% sequence identity thereof; the HCDR2 sequence comprises NIDPYYGGTSYNQKFKG (SEQ ID NO: 2), or a homologue sequence of at least 80% sequence identity thereof; the HCDR3 sequence comprises MYHGNAFDY (SEQ ID NO: 3), or a homologue sequence of at least 80% sequence identity thereof; the LCDR1 sequence comprises KSSQSLLNSGNLKNYLT (SEQ ID NO: 4) or a homologue sequence of at least 80% sequence identity thereof; the LCDR2 sequence comprises WASTRKS (SEQ ID NO: 5) or a homologue sequence of at least 80% sequence identity thereof; and the LCDR3 sequence comprises QNDYSYPLT (SEQ ID NO: 6) or a homologue sequence of at least 80% sequence identity thereof.
The anti-CLDN18.2 antigen binding region is further claimed as comprising a VH and a VL, wherein: the VH comprises an amino acid sequence of SEQ ID NO: 7 or a homologous sequence having at least 80% sequence identity thereof, and the VL comprises an amino acid sequence of SEQ ID NO: 8 or a homologous sequence having at least 80% sequence identity thereof.
The anti-CLDN18.2 antagonist is further claimed as a humanized antibody comprising a VH and a VL, wherein the VH comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14, and the VL comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 15 and SEQ ID NO: 16.
The co-pending application further claims a immunoglobulin human IgG constant region.
The co-pending application does not claim the anti-CLDN18.2 antibody is conjugated to a specific radioisotope for therapeutic or diagnostic purposes through a chelator, or the antagonist exists in various antigen-binding fragments, or as a pharmaceutical composition.
Qian discloses an anti-CLDN18.2 antibody that can be conjugated to a radioactive isotope. (See Qian pg. 27 [0398]). The conjugated isotope could be for diagnostic imaging and use 123I, 124I, 125I, 131I, 111In, 64Cu, 67Cu, 86Y, 90Y, 177Lu, 211At, 186Re, 153Sm, 212Bi, and 32P, (See Qian pg. 27 [0400]) and also for therapeutic purposes using 211At, 131I, 125I, 90Y, 186Re, 153Sm, 212Bi, 32P, and 212Pb (See Qian pg. 28 [0409]). The anti-CLDN18.2 antibody can be conjugated to the radioactive isotopes through a chelator, including DOTA, DTPA, and TETA. (See Qian pg. 28 [0409]). As evidenced by De Leon Rodriguez, DOTA contains eight chelation atoms, four of nitrogen and 4 of oxygen. (See De Leon Rodriguez, pg. 395 column 1, ‘Coordination Chemistry’).Qian also discloses the anti-CLDN18.2 antibody conjugate in a pharmaceutical composition. (See Qian, claim 51) and can be in the form of a diabody, a Fab, a Fab', a F(ab')2, a Fd, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a bispecific dsFv (dsFv-dsFv'), a disulfide stabilized diabody (ds diabody), a single-chain antibody molecule (scFv), an scFv dimer (bivalent diabody), or a multi-specific antibody (claim 37).
Qian does not disclose the antibody conjugate can be used with PET and SPECT imaging and where the radionuclide is 89Zr and the chelator is DFO.
Viola-Villegas teaches the radionuclide can be for diagnostic purposes and used with PET and SPECT imaging. (See Viola-Villegas pgs. 13-14 [0071]). Viola-Villegas also teaches a chelator attached to an antibody where the radionuclide is 89Zr and the chelator is DFO. (See Viola-Villegas, pg. 19[00102]).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective date to use the antibody of the co-pending application with the teachings of Qian and Viola-Villegas to produce the present claimed invention. It would have been obvious because the co-pending application claims conjugating an antibody to a radioactive isotope and Qian teaches conjugating an anti-CLDN18.2 antibody to radionuclides for therapeutic and diagnostic purposes as disclosed in the present claimed invention. Further, Viola-Villegas expands on the teachings of Qian to teach a specific radionuclide and chelator combination for use in therapeutic or diagnostic purposes. Therefore, it would have been obvious to a person of ordinary skill prior to the effective filing date to use the antibody claimed in the co-pending application with the teachings of Qian and Viola-Villegas to produce an anti-CLDN18.2 antibody conjugate for use with therapeutic and diagnostic radionuclides as claimed in the present invention with a reasonable expectation of success.
Co-Pending App #19489267
Present Application
SEQ ID NO:1 GYNMN
SEQ ID NO:1 GYNMN
SEQ ID NO:2 NIDPYYGGTSYNQKFKG
SEQ ID NO:32 [N/Y]IDPYY[G/V][A/G/T]T[R/T/S]YNQKF[K/R]G
SEQ ID NO:3 MYHGNAFDY
SEQ ID NO:33 [S/M][Y/F][Y/H]GNAFDY
SEQ ID NO:4 KSSQSLLNSGNLKNYLT
SEQ ID NO:34 KSSQ[S/N]L[L/F]N[S/N]GN[Q/L]KNYLT
SEQ ID NO:5 WASTRKS
SEQ ID NO:35 WASTR[E/K]S
SEQ ID NO:6 QNDYSYPLT
SEQ ID NO:36 QNDY[S/Y][F/Y]P[F/L]T
SEQ ID NOs:1, 19, and 21 are 100% matched in SEQ ID NO:7 (19/489,267):
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
3 158.4 86.6 118 US-17-636-373-45 2022-02-18 3 NOVEL ANTI- CLDN18.2 ANTIBODIES
ALIGNMENT:
Query Match 86.6%; Score 158.4; Length 118;
Best Local Similarity 40.3%;
Matches 31; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 GYNMN--------------NIDPYYGGTSYNQKFKG------------------------ 22
||||| |||||||||||||||||
Db 31 GYNMNWVKQSNGESLEWIGNIDPYYGGTSYNQKFKGKATLTVDKSSSTAYMQLKSLTSED 90
Qy 23 --------MYHGNAFDY 31
|||||||||
Db 91 SAVYYCARMYHGNAFDY 107
US-19-489-267-7
Filing date in PALM: N/A
Sequence 7, US/19489267
GENERAL INFORMATION
APPLICANT: SUZHOU TRANSCENTA THERAPEUTICS CO., LTD. (en)
TITLE OF INVENTION: COMBINATION THERAPIES INVOLVING CLAUDIN 18.2 ANTAGONISTS FOR TREATMENT OF CANCER (en)
FILE REFERENCE: 063694-8016WO03
CURRENT APPLICATION NUMBER: US/19/489,267
CURRENT FILING DATE: 2025-12-02
NUMBER OF SEQ ID NOS: 37
SEQ ID NO 7
LENGTH: 118
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..118
QUALIFIERS: note = Synthetic
FEATURE:
NAME/KEY: source
LOCATION: 1..118
QUALIFIERS: mol_type = protein
organism = synthetic construct
SEQ ID NOs:14, 16, and 18 are 100% matched in SEQ ID NO:8 (19/489,267):
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
2 147.3 85.6 113 US-17-636-373-46 2022-02-18 3 NOVEL ANTI- CLDN18.2 ANTIBODIES
ALIGNMENT:
Query Match 85.6%; Score 147.3; Length 113;
Best Local Similarity 41.2%;
Matches 33; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KSSQSLLNSGNLKNYLT---------------WASTRKS--------------------- 24
||||||||||||||||| |||||||
Db 24 KSSQSLLNSGNLKNYLTWYQQKPGQPPKLLIYWASTRKSGVPDRFTGSGSGTDFTLTLSS 83
Qy 25 -----------QNDYSYPLT 33
|||||||||
Db 84 VQAEDLAVYYCQNDYSYPLT 103
US-19-489-267-8
Filing date in PALM: N/A
Sequence 8, US/19489267
GENERAL INFORMATION
APPLICANT: SUZHOU TRANSCENTA THERAPEUTICS CO., LTD. (en)
TITLE OF INVENTION: COMBINATION THERAPIES INVOLVING CLAUDIN 18.2 ANTAGONISTS FOR TREATMENT OF CANCER (en)
FILE REFERENCE: 063694-8016WO03
CURRENT APPLICATION NUMBER: US/19/489,267
CURRENT FILING DATE: 2025-12-02
NUMBER OF SEQ ID NOS: 37
SEQ ID NO 8
LENGTH: 113
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..113
QUALIFIERS: note = Synthetic
FEATURE:
NAME/KEY: source
LOCATION: 1..113
QUALIFIERS: mol_type = protein
organism = synthetic construct
SEQ ID NO:25 is 100% identical to SEQ ID NO:12 (19/489,267):
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 634 100.0 118 US-17-636-373-25 2022-02-18 5 NOVEL ANTI- CLDN18.2 ANTIBODIES
ALIGNMENT:
Query Match 100.0%; Score 634; Length 118;
Best Local Similarity 100.0%;
Matches 118; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYNMNWVRQAPGQGLEWMGNIDPYYGGTSY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYNMNWVRQAPGQGLEWMGNIDPYYGGTSY 60
Qy 61 NQKFKGRVTMTIDKSTSTVYMELSSLRSEDTAVYYCARMYHGNAFDYWGQGTTVTVSS 118
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFKGRVTMTIDKSTSTVYMELSSLRSEDTAVYYCARMYHGNAFDYWGQGTTVTVSS 118
US-19-489-267-12
Filing date in PALM: N/A
Sequence 12, US/19489267
GENERAL INFORMATION
APPLICANT: SUZHOU TRANSCENTA THERAPEUTICS CO., LTD. (en)
TITLE OF INVENTION: COMBINATION THERAPIES INVOLVING CLAUDIN 18.2 ANTAGONISTS FOR TREATMENT OF CANCER (en)
FILE REFERENCE: 063694-8016WO03
CURRENT APPLICATION NUMBER: US/19/489,267
CURRENT FILING DATE: 2025-12-02
NUMBER OF SEQ ID NOS: 37
SEQ ID NO 12
LENGTH: 118
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..118
QUALIFIERS: note = Synthetic
FEATURE:
NAME/KEY: source
LOCATION: 1..118
QUALIFIERS: mol_type = protein
organism = synthetic construct
SEQ ID NO:26 is 100% identical to SEQ ID NO:15 (19/489,267):
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 593 100.0 113 US-17-636-373-26 2022-02-18 5 NOVEL ANTI- CLDN18.2 ANTIBODIES
ALIGNMENT:
Query Match 100.0%; Score 593; Length 113;
Best Local Similarity 100.0%;
Matches 113; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNLKNYLTWYQQKPGQPPKLLIYWASTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNLKNYLTWYQQKPGQPPKLLIYWASTR 60
Qy 61 KSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPLTFGGGTKVEIK 113
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPLTFGGGTKVEIK 113
US-19-489-267-15
Filing date in PALM: N/A
Sequence 15, US/19489267
GENERAL INFORMATION
APPLICANT: SUZHOU TRANSCENTA THERAPEUTICS CO., LTD. (en)
TITLE OF INVENTION: COMBINATION THERAPIES INVOLVING CLAUDIN 18.2 ANTAGONISTS FOR TREATMENT OF CANCER (en)
FILE REFERENCE: 063694-8016WO03
CURRENT APPLICATION NUMBER: US/19/489,267
CURRENT FILING DATE: 2025-12-02
NUMBER OF SEQ ID NOS: 37
SEQ ID NO 15
LENGTH: 113
TYPE: PRT
FEATURE:
NAME/KEY: REGION
LOCATION: 1..113
QUALIFIERS: note = Synthetic
FEATURE:
NAME/KEY: source
LOCATION: 1..113
QUALIFIERS: mol_type = protein
organism = synthetic construct
Conclusion
13. Claims 1-2, 4-5, 8-13, 18, 21, and 24-26 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LINDSAY DUNN whose telephone number is (571)272-5825. The examiner can normally be reached Monday-Friday 8-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LINDSAY DUNN/Examiner, Art Unit 1644
/Laura B Goddard/Primary Examiner, Art Unit 1642
Prosecution Insights