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 .
Claims Status
Claims 1, 6-7, 11, 14, 19, and 25 are amended.
Claims 4-5 and 8-9 are cancelled.
Claims 1-3, 6-7, and 10-34 are pending and are examined on the merits.
Objections Withdrawn
All objections to the claims with regard to drawings and specification are withdrawn in view of Applicant’s amendments.
Rejections Withdrawn
Claims 4-5 and 8-9 are cancelled, rendering all previous rejections moot.
Rejection of claims 7, 11, 19, and 25 under 35 U.S.C. §112(b) are withdrawn with Applicant amendment of the claim.
New Objections necessitated by Claims Amendments
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because the “Sequence Listing XML,” as a separate part of the disclosure, is defective, damaged or unreadable. Specifically, SEQ ID NOs: 80-82 are used to describe a caspase-cleavable peptide linker that comprises four C-terminal amino acid residues and it is a skipped sequence in the sequence listing, which should be removed. The sequence listing and CRF were entered under ST26 where sequence identifiers corresponding to 3 amino acids or less are shown as skipped sequences.
Refer to document “Sequence Listing (XML file)” dated 7/28/2026.
Required response - Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above submitted in accordance with either item 1. or 2.; together with
o A statement that identifies the location of all additions, deletions or replacements of sequence information relative to the replaced “Sequence Listing XML” as required by 37 CFR 1.835(b)(3);
o A statement that indicates support for the replacement “Sequence Listing XML” in the application, as filed, as required by 37 CFR 1.835(b)(4); and
o A statement that the replacement “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(b)(5).
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125, inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because of the following informalities:
Throughout the specification, SEQ ID NOs:80-82 are used to describe a caspase-cleavable peptide linker that comprises four C-terminal amino acid residues and it is a skipped sequence in the sequence listing. The sequence listing and CRF were entered under ST26 where sequence identifiers corresponding to 3 amino acids or less are shown as skipped sequences. Applicant is required to amend the specification of all the sequence identifiers corresponding to a skipped sequence with the specific sequences. See pages 3 and 32-33.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities:
SEQ ID NOs:80-82 are skipped sequences in the sequence listing and CRF. The amino sequences recited in claim 1 should be recited without the sequence identifiers.
Appropriate correction is required.
Rejections Maintained
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-3, 6-7, 10-16, and 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (US Patent No. 10,357,572 B2; hereinafter Kim ‘572), and further in view of Kim et al (US Patent No. 11,912,760 B2; hereinafter Kim ‘760).
Regarding instant claims 1-3, 6-7, 10-16, and 26-27, Kim ‘572 teaches prodrug conjugates comprising: (i) a functional moiety, (II) a caspase-cleavable peptide linker, and (iii) a chemotherapeutic agent, wherein the functional moiety is selected from the group consisting of antibodies, proteins, and aptamers that bind selectively to tumor cells or tumor endothelial cells and the caspase-cleavable peptide linker is cleavable by intracellular proteases, e.g. caspase-3, caspase-7, and caspase-9, and the conjugates described herein are used in methods of treating cancer (instant claims 1 and 4; page 18, column 2, lines 8-45). Kim ‘572 additionally teaches that the four C-terminal amino acid residues of the caspase-cleavable peptide linker are selected from the group consisting of Asp-Xaa-Xaa-Asp, Leu-Xaa-Xaa-Asp, and Val-Xaa-Xaa-Asp, where Xaa represents any amino acid residue, wherein the four C-terminal amino acid residues of the caspase-cleavable peptide linker are selected from the group consisting of Asp-Glu-Val-Asp, Asp-Leu-Val-Asp, Asp-Glu-Ile-Asp, and Leu-Glu-His-Asp (instant claims 1 and 6; page 18, column 2, lines 43-55). Kim ‘572 also teaches that the six C-terminal amino acid residues of the caspase-cleavable peptide linker consist of Lys-Gly-Asp-Glu-Val-Asp (instant claim 7; page 18, column 2, lines 55-58). Kim ‘572 further teaches that the chemotherapeutic agent induces apoptosis of tumor cells wherein the chemotherapeutic agent is selected from the group consisting of anthracyclines, doxorubicin, bleomycin, monomethyl auristatin E, etc., and derivatives thereof (instant claims 10-16; page 18, column 2, line 59 - page 19, column 3, lines 1-19). Finally, Kim ‘572 teaches a pharmaceutical composition comprising the prodrug conjugate and a pharmaceutically accepted carrier (instant claim 26, page 22, column 10, lines 17-46), wherein the pharmaceutical composition may be prepared for intravenous injection (instant claim 27, page 22, column 10, lines 28-33).
However, Kim ‘572 does not teach and antibody drug conjugate comprising a doppel-targeting moiety that binds to doppel, wherein the doppel-targeting moiety is a monoclonal antibody wherein the antibody is human monoclonal antibody 3H9.
The deficiency is resolved by Kim ‘760.
Kim ‘760 teaches a doppel-targeting molecule, including antibodies and fragments thereof, useful for inhibiting pathological angiogenesis and treating diseases and conditions associated with pathological angiogenesis, such as cancers (e.g. breast carcinoma, lung carcinoma, colorectal carcinoma, etc.), atherosclerosis, tuberculosis, asthma, and pulmonary arterial hypertension (PAH) (page 33, column 1, lines 21-26). Kim ‘760 also teaches that the doppel-targeting molecules that bind to doppel may be an antibody, wherein the antibody can be a human antibody, a monoclonal antibody, a chimeric antibody, or a humanized antibody (instant claim 2; page 33, column 1, lines 44-50). Kim ‘760 further teaches a doppel-binding human monoclonal antibody selected from a human monoclonal antibody A12, human monoclonal antibody B2, human monoclonal antibody E9, human monoclonal antibody 3D5, human monoclonal antibody 3D1, human monoclonal antibody 4D1, human monoclonal antibody 3H9, or doppel-binding fragments of any thereof (instant claim 3; page 35, column 6, lines 53-63).
Regarding instant claims 1-3, 6 and 8, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the prodrug conjugate comprising: (i) a functional moiety, (II) a caspase-cleavable peptide linker, wherein the caspase-cleavable peptide linker is cleavable by intracellular proteases and comprises four C-terminal amino acid residues comprising Asp-Glu-Val-Asp, and (iii) a chemotherapeutic agent as taught by Kim ‘572 and substitute the functional moiety with a doppel-binding human monoclonal antibody where in the antibody is a human monoclonal antibody 3H9, as taught by Kim ‘760. This is obvious because, Kim ‘572 teaches prodrug conjugates comprising: i) a functional moiety wherein the functional moiety is an antibody; ii) a caspase-cleavable peptide linker wherein the caspase-cleavable peptide linker is cleavable by intracellular proteases, e.g. caspase-3, caspase-7, and caspase-9 and comprises four C-terminal amino acid residues Asp-Glu-Val-Asp; and iii) a chemotherapeutic agent, and Kim ‘760 teaches a doppel-targeting molecule, including antibodies and fragments thereof, useful for inhibiting pathological angiogenesis and treating diseases and conditions associated with pathological angiogenesis, such as cancer or pulmonary arterial hypertension, wherein the doppel-targeting moiety is a doppel-binding human monoclonal antibody, e.g. human monoclonal antibody 3H9. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant anti-doppel antibody drug conjugate (ADC) comprising: i) a doppel-targeting moiety that binds to doppel wherein the instant doppel-targeting moiety is a monoclonal antibody, e.g. human monoclonal antibody 3H9, joined directly to, ii) a caspase-cleavable peptide linker wherein the instant caspase-cleavable peptide linker is cleavable by intracellular proteases and comprises four C-terminal amino acid residues Asp-Glu-Val-Asp, joined directly to, iii) a therapeutic agent.
Regarding instant claim 7, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a caspase-cleavable peptide linker joined directly to, iii) a therapeutic agent as taught by the combined teachings of Kim ‘572 and Kim ‘760 and further modify the amino acid sequence of the caspase-cleavable peptide linker wherein the amino acid sequence comprises Lys-Gly-Asp-Glu-Val-Asp as taught by Kim ‘572. This is obvious because, Kim ‘572 teaches prodrug conjugates comprising a functional moiety wherein the functional moiety is an antibody; a caspase-cleavable peptide linker wherein the caspase-cleavable peptide linker comprises the amino acid sequence Lys-Gly-Asp-Glu-Val-Asp; and a chemotherapeutic agent, and Kim ‘760 teaches a doppel-targeting moiety, including antibodies and fragments thereof, useful for treating diseases and conditions associated with pathological angiogenesis, such as cancer or pulmonary arterial hypertension. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant anti-doppel ADC comprising: i) a doppel-targeting moiety that binds to doppel, joined directly to, ii) a caspase-cleavable peptide linker wherein the instant caspase-cleavable peptide linker comprises Lys-Gly-Asp-Glu-Val-Asp, joined directly to, iii) a therapeutic agent.
Regarding instant claims 10-16 and 26-27, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the pharmaceutical composition comprising the anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a cleavable linker joined directly to, iii) a therapeutic agent and a pharmaceutically acceptable carrier wherein the pharmaceutical composition is formulated for intravenous administration as taught by the combined teachings of Kim ‘572 and Kim ‘760 and further modify the therapeutic agent to comprise a chemotherapeutic agent wherein the chemotherapeutic agent comprises anthracyclines, doxorubicin, bleomycin, or monomethyl auristatin E (MMAE) as taught by Kim ‘572. This is obvious because, Kim ‘572 teaches a pharmaceutical composition formulated for intravenous administration comprising prodrug conjugates comprising a functional moiety wherein the functional moiety is an antibody; a cleavable peptide linker; and a therapeutic agent wherein the therapeutic agent is a chemotherapeutic agent comprising anthracyclines, doxorubicin, bleomycin, or MMAE, and Kim ‘760 teaches a doppel-targeting moiety, including antibodies and fragments thereof, useful for treating diseases and conditions associated with pathological angiogenesis, such as cancer or pulmonary arterial hypertension. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to form the instant pharmaceutical composition formulated for intravenous administration comprising the instant ADC and a pharmaceutically acceptable carrier, wherein the anti-doppel ADC comprises: i) a doppel-targeting moiety that binds to doppel, joined directly to, ii) a cleavable linker, joined directly to, iii) a therapeutic agent wherein the instant therapeutic agent is a chemotherapeutic agent that comprises anthracyclines, doxorubicin, bleomycin, or MMAE.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (US Patent No. 10,357,572 B2; hereinafter Kim ‘572) and Kim et al (US Patent No. 11,912,760 B2; hereinafter Kim ‘760) as applied to claim 1 above, and further in view of Viricel (WO2023170247A1, priority to 3/11/2022; hereinafter Viricel).
The teachings of Kim ‘572 and Kim ’760 are discussed above.
However, the combined teachings of Kim ‘572 and Kim ‘760 do not teach an antibody drug conjugate wherein the cleavable linker is selected from a dipeptide cleavable linker wherein the dipeptide is valine-citrulline, and the therapeutic agent comprises a chemotherapeutic agent wherein the chemotherapeutic agent is exatecan.
The deficiency is resolved by Viricel.
Viricel teaches antibody drug conjugates (ADC) useful in treating proliferative diseases including cancers, wherein the drug is chosen among inhibitors of topoisomerase I, e.g. camptothecin analogues such as exatecan (page 2, lines 3-7; page 5, lines 20-22). Furthermore, Viricel teaches that the linker of the ADC is a cleavable peptide moiety, wherein the cleavable peptide moiety is selected from the group consisting of valine-citrulline, valine-alanine, and phenylalanine-lysine, or a disulfide moiety (page 6, lines 2-10).
Regarding instant claim 17, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a cleavable linker joined directly to, iii) a therapeutic agent as taught by the combined teachings of Kim ‘572 and Kim ‘760 and further modify the cleavable linker to a valine-citrulline dipeptide cleavable linker and the therapeutic agent to a chemotherapeutic agent wherein the chemotherapeutic agent is exatecan as taught by Viricel. This is obvious because the combined teachings of Kim ‘572 and Kim ‘760 teach an anti-doppel ADC comprising a functional moiety wherein the functional moiety is a doppel-targeting antibody, a cleavable peptide linker, and a therapeutic agent, and Viricel teaches ADCs useful in treating proliferative diseases including cancers, wherein the ADC comprises a drug moiety, e.g. exatecan, and a cleavable peptide linker, wherein the cleavable peptide moiety is valine-citrulline. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to form the instant ADC comprising: i) a doppel-targeting moiety that binds to doppel, joined directly to, ii) a cleavable linker wherein the instant linker is a dipeptide cleavable linker comprising valine-citrulline, joined directly to, iii) a therapeutic agent wherein the instant therapeutic agent is the chemotherapeutic agent exatecan.
Claims 18-24 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (US Patent No. 10,357,572 B2; hereinafter Kim ‘572) and Kim et al (US Patent No. 11,912,760 B2; hereinafter Kim ‘760) as applied to claim 1 above, and further in view of Lippincott et al (U.S. Patent No 10,766,959; hereinafter Lippincott).
The teachings of Kim ‘572 and Kim ’760 are discussed above.
However, the combined teachings of Kim ‘572 and Kim ‘760 do not teach an antibody drug conjugate wherein the therapeutic agent is an immunomodulatory agent (e.g. granulocyte-colony stimulating factor (G-CSF)), a toxin (e.g. diphtheria toxin), a radionuclide (e.g. 90Y), or a DNA cross-linking agent (e.g. pyrrolobenzodiazepine (PBD)). Furthermore, the combined teachings of Kim ‘572 and Kim ‘760 do not teach a kit comprising the ADC.
The deficiency is resolved by Lippincott et al.
Lippincott teaches antibodies and antibody drug conjugates (ADC), and use of the antibodies and ADCs for the treatment of cancer, e.g. breast cancer (page 57, column 1, line 65-column 2, line 3; page 59, column 5, line 48-52). Lippincott additionally teaches that the antibodies or ADCs can be administered in combination with other therapeutic agents, such as immunomodulatory agents, wherein the immunomodulatory agent is interferons (IFN), tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), interleukins (IL), granulocyte-colony stimulating factor (G-CSF), or granulocyte macrophage-colony stimulating factor (GM-CSF) (page 72, column 31, lines 14-19; page 150, column 188, lines, 22-39). Furthermore, Lippincott teaches that the therapeutic moiety of the ADC comprises: 1) toxins e.g. abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin (page 150, column 188, lines 13-22); 2) radionuclides, or radioactive materials e.g. 67Ga, 90Y, 99Mo, 111In, 131I or 166Ho (page 149, column 186, line 61-page 150, column 187, line 4) ; and/or 3) a DNA cross-linking agent, e.g. pyrrolobenzodiazepine (PBD) (page 68, column 23, lines 5-47; page 68, column 23, line 64-column 24, line 14). Lastly, Lippincott teaches a kit comprising the ADC (page 78, column 44, lines 41-44).
Regarding instant claims 18-24, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a cleavable linker joined directly to, iii) a therapeutic agent as taught by the combined teachings of Kim ‘572 and Kim ‘760 and modify so that the therapeutic agent comprises: i) an immunomodulatory agent, e.g. GM-CSF (instant claim 18 and 19); ii) a toxin, e.g. diphtheria toxin (instant claims 20 and 21); iii) a radionuclide, e.g. 90Y (instant claims 22 and 23); and/or iv) a DNA cross-linking agent, e.g. PBD (instant claim 24) as taught by Lippincott. This is obvious because the combined teachings of Kim ‘572 and Kim ‘760 teach an anti-doppel ADC comprising a functional moiety wherein the functional moiety is a doppel-targeting antibody, a cleavable peptide linker, and a therapeutic agent, and Lippincott teaches ADCs wherein the ADCs can be administered in combination with other therapeutic agents, such as immunomodulatory agents, e.g. GM-CSF; toxins, e.g. diphtheria toxin; radionuclides, e.g. 90Y; and/or a DNA cross-linking agent, e.g. PBD. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant ADC comprising: i) a doppel-targeting moiety that binds to doppel, joined directly to, ii) a cleavable linker, joined directly to, iii) a therapeutic agent wherein the instant therapeutic agent comprises an immunomodulatory agent, e.g. GM-CSF; a toxin, e.g. diphtheria toxin; a radionuclide, e.g. 90Y; and/or a DNA cross-linking agent, e.g. PBD.
Regarding instant claim 31, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a cleavable linker joined directly to, iii) a therapeutic agent as taught by the combined teachings of Kim ‘572 and Kim ‘760 and form a kit comprising the ADC as taught by Lippincott. This is obvious because the combined teachings of Kim ‘572 and Kim ‘760 teach an anti-doppel ADC comprising a functional moiety wherein the functional moiety is a doppel-targeting antibody; a cleavable peptide linker, and a therapeutic agent, and Lippincott teaches a kit comprising the ADC, wherein the ADCs are used for treatment of cancer. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form a kit comprising the ADC as taught by Lippincott to form the instant kit comprising the ADC wherein the instant ADC comprises: i) a doppel-targeting moiety that binds to doppel, joined directly to, ii) a cleavable linker, joined directly to, iii) a therapeutic agent.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (US Patent No. 10,357,572 B2; hereinafter Kim ‘572) and Kim et al (US Patent No. 11,912,760 B2; hereinafter Kim ‘760) as applied to claim 1 above, and further in view of Gikanga et al (Bioconjugate Chemistry, 2016, 27(4):1040-1049; hereinafter Gikanga).
The teachings of Kim ‘572 and Kim ’760 are discussed above.
However, the combined teachings of Kim ‘572 and Kim ‘760 do not teach an antibody drug conjugate (ADC) wherein the ADC is 3H9-vc-MMAE.
The deficiency is resolved by Gikanga et al.
Gikanga teaches a valine-citrulline-monomethyl auristatin E (vc-MMAE)-based ADC molecules that are designed to deliver microtubule destabilizing MMAE to cancer cells, wherein the vc-MMAE based ADCs are conjugated onto monoclonal antibodies (mAbs) through a protease-cleavable dipeptide valine-citrulline (vc) linker (page 1040, Abstract; page 1040, first and second paragraphs). Gikanga further teaches that when a selection of four IgG1 antibody-based ADC molecules with different charge and hydrophobicity in the CDR region was compared, there was no difference in protease catalytic activities. Furthermore, Gikanga teaches that when a comparison between ADC and small molecule substrates in the steady state kinetic experiment of cathepsin was performed, there was no impact on drug release with or without a protein carrier in the ADC construct. Gikanga discloses that these results point to consistent substrate accessibility and cleavage rate in a variety of vc-MMAE-based substrates (page 1046, Conclusion Section)
Regarding instant claim 25, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a cleavable linker joined directly to, iii) a therapeutic agent as taught by the combined teachings of Kim ‘572 and Kim ‘760 and substitute the human monoclonal anti-doppel antibody 3H9 (taught by Kim ‘572) for the doppel-targeting moiety and vc-MMAE for the cleavable linker and therapeutic agent as taught by Gikanga. This is obvious because the combined teachings of Kim ‘572 and Kim ‘760 teach an anti-doppel ADC comprising a functional moiety wherein the functional moiety is a doppel-targeting antibody; a cleavable peptide linker, and a therapeutic agent, and Gikanga teaches vc-MMAE-based ADC molecules that are designed to deliver microtubule destabilizing MMAE to cancer cells, wherein the vc-MMAE based ADCs are conjugated onto monoclonal antibodies through a protease-cleavable dipeptide valine-citrulline linker. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant ADC 3H9-vc-MMAE.
Claims 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (US Patent No. 10,357,572 B2; hereinafter Kim ‘572) and Kim et al (US Patent No. 11,912,760 B2; hereinafter Kim ‘760) as applied to claim 1 above, and further in view of Al-Hilal et al (J Clin Invest, 2016, 126(4): 1251-1266; hereinafter Al-Hilal).
The teachings of Kim ‘572 and Kim ’760 are discussed above.
However, the combined teachings of Kim ‘572 and Kim ‘760 do not teach types of cancer wherein the cells of the cancer express doppel.
The deficiency is resolved by Al-Hilal et al.
Al-Hilal teaches Doppel, a prion-like protein, has recently been rediscovered as a tumor endothelial cell (TEC)-specific surface marker wherein doppel is expressed in clinical and preclinical cancer samples but not in normal endothelium (page 1251, second and third paragraphs). Al-Hilal also teaches that doppel was expressed in cancers, such as colorectal cancer, brain cancer, breast cancer, and lung cancer; however, nonendothelium-based tumors, such as head and neck cancer, expressed very little doppel (Figure 9, page 1261, second paragraph – page 1262, paragraph continued).
Regarding instant claims 28-30, it would have been obvious for a person having ordinary skill in the art at the time of filing to use the anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a cleavable linker joined directly to, iii) a therapeutic agent in a method for treating a doppel-associated condition in a subject comprising administering to a subject in need thereof the ADC wherein the doppel-associated disease or condition is pulmonary arterial hypertension or cancer (e.g. breast carcinoma) as taught by the combined teachings of Kim ‘572 and Kim ‘760, wherein cells of the cancer, such as breast cancer, express doppel as taught by Al-Hilal. This is obvious because the combined teachings of Kim ‘572 and Kim ‘760 teach an anti-doppel ADC comprising a functional moiety wherein the functional moiety is a doppel-targeting antibody; a cleavable peptide linker, and a therapeutic agent wherein the ADC is used to treat a doppel-associated condition in a subject comprising administering to a subject in need thereof the ADC wherein the doppel-associated disease or condition is pulmonary arterial hypertension or cancer (e.g. breast carcinoma), and Al-Hilal teaches Doppel, a prion-like protein, has recently been rediscovered as a TEC-specific surface marker wherein doppel is expressed in cancers, such as colorectal cancer, brain cancer, breast cancer, and lung cancer. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant method for treating a doppel-associated disease or condition in a subject, comprising administering to a subject in need thereof the ADC wherein the doppel-associated disease or condition in the instant application is pulmonary arterial hypertension or cancer wherein the cells of the cancer express doppel.
Applicant Arguments
Applicant argues the following points:
The conjugates of Kim ‘572 rely on different mechanisms of action such that modifying them in the manner asserted for the rejection above would alter their principle of operation;
There are unexpected advantageous properties of the claimed ADCs, including: a radiation-free activation cascade, a bystander effect and a self-amplifying feedback loop, and a diffusion profile extending from tumor vasculature into deep tissue; and
While Kim ‘572’s maleimide-containing conjugates are said to bind albumin for prolonged plasma half-life, in the instant claimed ADCs, the maleimide is consumed in conjugation and is unavailable for albumin binding.
Response to Arguments
Applicant's arguments filed 7/28/2026 and the Declaration under 37 C.F.R. 1.132 of Dr. Youngro Byun have been fully considered but they are not persuasive.
In regards to the unexpected results, first of all, a showing of unexpected results must be commensurate in scope with the claims sought to be patented. See. MPEP 716.02(d). All data of record employs a single doppel-targeting antibody (e.g. 3H9), a single payload (e.g. MMAE), and a KGDEVD or DEVD linker. Amended claim 1 encompasses any doppel-targeting moiety, any therapeutic agent, and a caspase-cleavable peptide linker whose four C-terminal residues are drawn from three motifs in which “Xaa” may be any amino acid residue at two of the four positions. However, the self-amplifying feedback effect disclosed in the Byun Declaration (paragraphs 13 and 15) requires a payload that induces caspase-3/7 dependent apoptosis so that the released agent generates the protease that cleaves the linker. Additionally, the bystander effect requires a membrane-permeable released agent. Instant claim 1 limits the therapeutic agent in neither respect, and new claims 32-34 recite immunomodulatory payloads, namely TLR agonists, imidazoquinoline derivatives, and CpG oligonucleotides, which are not apoptosis-inducing cytotoxins. Regarding the linker, caspase recognition is sequence dependent, yet the claimed motifs permit any amino acid residue at two of four positions and place no limit on the residues N-terminal to the motif. No data of record addresses any linker other than KGDEVD and DEVD, and therefore, there is no basis to conclude that the argued dual protease susceptibility, cleavage behavior, or tumor penetration would be retained across the claimed motifs. Thus, the Applicant has not shown that species to be representative of the claimed genus and therefore, is not commensurate in scope with the instant claims.
Secondly, disclosing unexpected results must compare the claimed subject matter against the closest prior art. See MPEP 716.02(e). The Ig-KGDEVD-MMAE of Kim ‘760, which is compared to Figure 3 disclosed in the Byun Declaration, does not comprise a doppel-targeting moiety. Furthermore, 3H9-ValCit-MMAE of Kim ‘572, which is compared to Figure 5 disclosed in the Byun Declaration, does not comprise a caspase-cleavable linker. Thus, neither of the products that are compared to the claimed invention represent the product of the combination of Kim ‘572 and Kim ‘760. Therefore, the unexpected results establishes only that each claimed element contributes to activity, not that the claimed instant ADC differs unexpectedly from what the combination would have produced.
In regards to Exhibit A disclosed in the Byun Declaration, Exhibit A reports a Trastuzumab-DEVD construct exhibiting the bystander effect. The result indicates that the argued bystander effect tracks the DEVD linker itself rather than the doppel-targeting moiety, and Applicant concedes in footnote 1 (page 3 of the Byun Declaration) that Kim ‘572 discloses conjugates having a DEVD linker. Therefore, Exhibit A attributes the advantage to an element already provided by the prior art referenced in the rejection. Furthermore, an anti-HER2 ADC is not encompassed by the instant claims, and thus not representative of the claimed anti-doppel ADCs.
The Applicant’s arguments address radiation dependence, intracellular cathepsin B versus extracellular caspase-3 cleavage, bystander effect, self-amplifying feedback, diffusion profile, and albumin binding. However, instant claims 1-3, 6-7, 10-27, and 31-34 are composition, pharmaceutical composition, and kit claims, and the patentability of a composition focuses on the composition itself rather than on its mode of activation. See MPEP 2112.01 and 2114. Additionally, the radiation step of Kim ‘572 is a condition of use, and a composition claim is not limited by the manner in which the prior art proposes to use the composition. Furthermore, the Applicant has not identified any structural element of the instantly claimed ADC that is absent from the combined teachings of Kim ‘572 and Kim ‘760.
Regarding the assertion of altering the principle of operation, under In re Ratti (MPEP 2143.01), the inquiry is whether the proposed modification changes the principle of operation of the primary reference. Kim ‘572 recites functional moieties selected from antibodies, proteins and aptamers that bind selectively to tumor cells or tumor endothelial cells (page 18, column 2, lines 8-45). Substituting a doppel-binding, tumor-endothelial cell-binding antibody would allow the ADC of Kim ‘572 to operate as designed, not an alteration of its principle of operation. In regards to Kim ‘760, Kim ‘760’s purpose is to treat diseases and conditions associated with pathological angiogenesis, such as cancer. In paragraph 10 of the Byun Declaration, the Applicant concedes that the instantly claimed ADCs reduce tumor vessel density. The Applicant attributes that reduction most likely is due to the cytotoxic payload rather than doppel binding, but the attribution is not supported by any comparisons or data isolating the contribution of the doppel-targeting moiety. Either way, Kim ‘760’s intended purpose is treating angiogenesis-associated disease, e.g. cancer, and the modified molecule discussed in the rejections achieves that purpose.
Finally, in regards to albumin binding, the Applicant compares the plasma half-life of Kim ‘572’s maleimide conjugates with that of the claimed ADCs. Circulating half-life is a property of the administered composition, not a structural limitation of instant claim 1, and the difference that the Applicant identifies follows from how the maleimide is consumed rather than from any structural element missing from the combined teachings. Additionally, this argument is not commensurate in scope with instant claim 1, since instant claim 1 does not require a maleimide.
Therefore, the rejections set forth above are maintained.
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.
Claim 1-3 and 26-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-6, 13-19, and 26 of U.S. Patent No. 11,912,760 B2 (Kim et al; hereinafter Kim ‘760) and further in view of Kim et al (US Patent No. 10,357,572 B2; hereinafter Kim ‘572) and Al-Hilal et al (J Clin Invest, 2016, 126(4): 1251-1266; hereinafter Al-Hilal). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1-2, 4-6, 13-19, and 26 of Kim ‘760 in view of Kim ‘572 and Al-Hilal teach the limitations of the instant claims 1-3, and 26-30 for the reasons discussed above in the 103 rejection.
Furthermore, claims 1, 2, and 26 of Kim ‘760 teach specific amino acid sequences that comprise the doppel-targeting molecule, wherein the sequences listed in claims 1, 2, and 26, (m)-(s) correspond to the human monoclonal antibodies A12, B2, E9, 3D5, 3D1, 4D1, and 3H9, respectively, recited in instant claim 3. Claim 4, (p)-(s) of Kim ‘760 recite amino acid sequences of heavy and light chain regions of the doppel-targeting molecule, wherein the doppel-targeting molecules listed in parts (p)-(s) correspond to the human monoclonal antibodies 3D5, 3D1, 4D1, and 3H9, respectively, recited in the instant application (See specification pages 44-49, Tables 2-5).
However, the claims of Kim ‘760 do not teach an ADC comprising a doppel-targeting moiety that binds to doppel, joined directly to a cleavable linker, joined directly to a therapeutic agent.
The deficiency is resolved by Kim ‘572.
The teachings of Kim ‘572 are discussed above in the 103 rejection.
Regarding instant claims 1-3, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the prodrug conjugate comprising: (i) a functional moiety, (II) a cleavable linker, and (iii) a chemotherapeutic agent as taught by Kim ‘572 and substitute the functional moiety with a doppel-binding human monoclonal antibody where in the antibody is a human monoclonal antibody 3H9 as taught by Kim ‘760. This is obvious because, Kim ‘572 teaches prodrug conjugates comprising a functional moiety wherein the functional moiety is an antibody; a cleavable linker; and a chemotherapeutic agent, and Kim ‘760 teaches a doppel-targeting molecule, including antibodies and fragments thereof, useful for inhibiting pathological angiogenesis and treating diseases and conditions associated with pathological angiogenesis, such as cancers, wherein the doppel-targeting molecule is a doppel-binding human monoclonal antibody, e.g. human monoclonal antibody 3H9. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant anti-doppel antibody drug conjugate (ADC) comprising: i) a doppel-targeting moiety that binds to doppel wherein the instant doppel-targeting moiety is a monoclonal antibody, e.g. human monoclonal antibody 3H9, joined directly to, ii) a cleavable linker, joined directly to, iii) a therapeutic agent.
Regarding instant claims 26-27, it would have been obvious for a person having ordinary skill in the art at the time of filing to take the anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a cleavable linker joined directly to, iii) a therapeutic agent as taught by the combined teachings of Kim ‘572 and Kim ‘760 to form a pharmaceutical composition comprising the anti-doppel ADC and a pharmaceutically acceptable carrier wherein the pharmaceutical composition is formulated for intravenous administration as taught by Kim ‘572. This is obvious because, Kim ‘572 teaches a pharmaceutical composition formulated for intravenous administration comprising a prodrug conjugate and a pharmaceutically acceptable carrier, wherein the prodrug conjugate comprises a functional moiety wherein the functional moiety is an antibody; a cleavable peptide linker; and a therapeutic agent, and Kim ‘760 teaches a doppel-targeting moiety, including antibodies and fragments thereof, useful for treating diseases and conditions associated with pathological angiogenesis, such as cancer or pulmonary arterial hypertension. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant pharmaceutical composition formulated for intravenous administration comprising the instant ADC and a pharmaceutically acceptable carrier, wherein the instant ADC comprises: i) a doppel-targeting moiety that binds to doppel, joined directly to, ii) a cleavable linker, joined directly to, iii) a therapeutic agent.
Regarding instant claims 28-30, it would have been obvious for a person having ordinary skill in the art at the time of filing to use the anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a cleavable linker joined directly to, iii) a therapeutic agent in a method for treating a doppel-associated condition in a subject comprising administering to a subject in need thereof the ADC wherein the doppel-associated disease or condition is pulmonary arterial hypertension or cancer (e.g. breast carcinoma) as taught by the combined teachings of Kim ‘572 and Kim ‘760, wherein cells of the cancer, such as breast cancer, express doppel as taught by Al-Hilal. This is obvious because the combined teachings of Kim ‘572 and Kim ‘760 teach an anti-doppel ADC comprising a functional moiety wherein the functional moiety is a doppel-targeting antibody; a cleavable peptide linker, and a therapeutic agent wherein the ADC is used to treat a doppel-associated condition in a subject comprising administering to a subject in need thereof the ADC wherein the doppel-associated disease or condition is pulmonary arterial hypertension or cancer (e.g. breast carcinoma), and Al-Hilal teaches Doppel, a prion-like protein, has recently been rediscovered as a TEC-specific surface marker wherein doppel is expressed in cancers, such as colorectal cancer, brain cancer, breast cancer, and lung cancer. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant method for treating a doppel-associated disease or condition in a subject, comprising administering to a subject in need thereof the ADC wherein the doppel-associated disease or condition in the instant application is pulmonary arterial hypertension or cancer wherein the cells of the cancer express doppel.
Response to Arguments
Applicant's arguments filed 7/28/2026 have been fully considered but they are not persuasive.
For the reasons discussed above in response to the arguments regarding the 103 rejections, the instantly claimed ADCs are not patentably distinct from the claims of Kim ‘760 in view of Kim ‘572 and Al-Hilal. Thus, the double patenting rejection is maintained.
New Rejections Necessitated by Claims Amendments
Claim Rejections - 35 USC § 112(d)
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.
Claim 25 is 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. Instant claim 25 depends from instant claim 1 and recites an ADC selected from a group that includes species comprising a “-vc-“ (valine-citrulline dipeptide) linker. Amended instant claim 1 requires that the cleavable linker be a caspase-cleavable peptide linker whose four C-terminal amino acid residues are selected from Asp-Xaa-Xaa-Asp, Leu-Xaa-Xaa-Asp, and -Cal-Xaa-Xaa-Asp, wherein the linker is cleavable by intracellular proteases. Valine-citrulline comprises a dipeptide of two residues and does not present the four C-terminal residues corresponding to any of the three recited motifs in instant claim 1. Additionally, valine-citrulline dipeptide linkers are not cleaved by caspases. Thus, the four species comprising a valine-citrulline linker fall outside the scope of instant claim 1 and therefore, instant claim 25 does not further limit instant 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.
Claim Rejections - 35 USC § 112(b)
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.
Claim 25 is 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.
Instant claim 25 recites species that are excluded by instant claim 1 from which it depends. It is unclear whether claim 25 is limited by the linker requirement of instant claim 1 or is intended to recite the four species comprising a “-vc-“ linker notwithstanding instant claim 1. A person of ordinary skill in the art would not be able to determine which subject matter is embraced by claim 25. Thus, the metes and bounds of instant claim 25 are indefinite.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (US Patent No. 10,357,572 B2; hereinafter Kim ‘572), Kim et al (US Patent No. 11,912,760 B2; hereinafter Kim ‘760), and Lippincott et al (U.S. Patent No 10,766,959; hereinafter Lippincott), as applied to claim 1 above, and further in view of Alonso et al (WO2018009916A1, hereinafter Alonso).
The teachings of Kim ‘572, Kim ‘760, and Lippincott are discussed above in the 103 rejections set forth in the previous office action.
However, the combined teachings of Kim ‘572, Kim ‘760, and Lippincott do not teach immunomodulatory agents, wherein the immunomodulatory agents are a TLR agonist or an imidazoquinoline derivative.
The deficiency is resolved by Alonso.
Alonso teaches an immunoconjugate and methods for treating cancer with the immunoconjugates, wherein the immunoconjugate comprises (1) an antibody construct comprising an antigen binding domain and an Fc domain; (2) an adjuvant moiety; and (3) a linker, wherein each adjuvant moiety is covalently bonded to the antibody construct via the linker (Page 1, Abstract). Alonso also teaches adjuvant moieties, including a TL2/6 agonist, Pam2CSK4 (page 9, ¶ [0065]-[0069]; page 151, ¶ [1008]; Fig 22P-22T) and gardiquimod (page 150, ¶ [1006]).
Regarding instant claims 32 and 33, it would have been obvious for a person having ordinary skill in the art at the time of filing to substitute the immunomodulatory agents, e.g. Pam2CSK4 or gardiquimod, as taught by Alonso for the immunomodulatory therapeutic agent of the anti-doppel ADC taught by the combined teachings of Kim ‘572, Kim ‘760, and Lippincott. This is obvious because, the combined teachings of Kim ‘572, Kim ‘760, and Lippincott teach an anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a cleavable linker joined directly to, iii) an immunomodulatory therapeutic agent, and Alonso teaches an immunoconjugate comprising an antibody, adjuvant moiety, and linker, wherein examples of adjuvant moieties include Pam2CSK4 and gardiquimod. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant ADC comprising a doppel-targeting moiety, joined directly to a cleavable linker, joined directly to an immunomodulatory agent, wherein the immunomodulatory agent is a TLR agonist (e.g. Pam2CSK4) or an imidazoquinoline derivative (e.g. gardiquimod).
Claim 34 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (US Patent No. 10,357,572 B2; hereinafter Kim ‘572), Kim et al (US Patent No. 11,912,760 B2; hereinafter Kim ‘760), and Lippincott et al (U.S. Patent No 10,766,959; hereinafter Lippincott), as applied to claim 1 above, and further in view of Epstein et al (US9,522,958B2; hereinafter Epstein).
The teachings of Kim ‘572, Kim ‘760, and Lippincott are discussed above in the 103 rejections set forth in the previous office action.
However, the combined teachings of Kim ‘572, Kim ‘760, and Lippincott do not teach immunomodulatory agents, wherein the immunomodulatory agent is a CpG oligodeoxynucleotide (ODN).
The deficiency is resolved by Epstein.
Epstein teaches a cancer therapeutic agent comprising a cancer targeting molecule linked to a CpG oligodeoxynucleotide (page 1, Abstract). Specifically, Epstein teaches chTNT-3/CpG immunoconjugates that comprises ODN 1826, wherein CpG 1826 has been shown to induce immunostimulatory activity in mice (page 19, column 25, Example 1; page 9, column 5-6, §Brief Description of the Figures; page 10, column 8, lines 12-24; FIG 2 and FIG 3).
Regarding instant claim 34, it would have been obvious for a person having ordinary skill in the art at the time of filing to substitute the immunomodulatory agent, ODN 1826, as taught by Epstein for the immunomodulatory therapeutic agent of the anti-doppel ADC taught by the combined teachings of Kim ‘572, Kim ‘760, and Lippincott. This is obvious because, the combined teachings of Kim ‘572, Kim ‘760, and Lippincott teach an anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a cleavable linker joined directly to, iii) an immunomodulatory therapeutic agent, and Epstein teaches an immunoconjugate comprising a cancer-targeting molecule linked to a CpG ODN, e.g. ODN 1826. Therefore, it is obvious to a skilled artisan with reasonable expectation of success to have been motivated to form the instant ADC comprising a doppel-targeting moiety, joined directly to a cleavable linker, joined directly to an immunomodulatory agent, wherein the immunomodulatory agent is ODN1826.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/J.H./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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