DETAILED ACTION
Claims 1-31 are pending in the instant application and being examined on the merit.
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 .
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Specifically, the Examiner is referring to the references listed in the specification on pages 2, 10-15, 27, and 29-32. Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings are objected to because:
Instant Figure 2 is a grayscale drawing of the internalization of 3H9 monoclonal antibody (mAb) into doppel-expressing cells (HCTEC) (page 7, paragraph [0027]). However, it is difficult to determine the internalization of the 3H9 monoclonal antibody based on the current grayscale image. Therefore, the figure is not able to be interpreted as currently drawn in grayscale.
Instant Figure 3 is a grayscale drawing of lysosomal colocalization of the 3H9 mAb in doppel-expressing cells (HCTEC) wherein it appears the grayscale images are supposed to represent different stains (page 7, paragraph [0028]). However, it is difficult to determine which grayscale gradient represents which stain in the merged image. Therefore, the figure is not able to be interpreted as currently drawn in grayscale.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). See page 3, paragraph [0011]; page 32, paragraph [0091]; and page 33, paragraph [0094].
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because of the following informalities:
The table on page 52-56 of the specification that describes the anti-doppel ADC structures is missing a title (e.g. “Table 7:…”).
Appropriate correction is required.
The use of the term Tween 61, Witepsol, and Texas red, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. All trademarks referenced herein should be identified as such with the appropriate notation:
Tween 61 (page 41, paragraph [0118]);
Witepsol (page 41, paragraph [0118]); and
Texas red (page 49, paragraph [0145]).
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 5, 11, 14, and 19 are objected to because of the following informalities:
Sequences appearing in Claim 5 require a sequence identifier (i.e. “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c).
“Epidophyllotoxin” should read “epipodophyllotoxin” (instant claim 11);
“Calicheamicin” should read “Calicheamycin” (instant claim 14);
“Interrerons” should read “interferons” (instant claim 19).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7, 11, 19 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.
Claim 7 recites the limitation "the caspase-cleavable peptide" in line 1. There is insufficient antecedent basis for this limitation in the claim. Regarding instant claim 7, the claim is dependent on claim 1, which recites a “cleavable linker” instead of a “caspase-cleavable linker”. Thus, the metes and bound of the claim are unclear as there is no antecedent basis. For the purposes of compact prosecution, claim 7 will be read as if dependent on claim 4. It should be noted that such treatment does not relieve Applicants of the responsibility of responding to this rejection. Moreover, if the intended meaning of the claim is different than that posited by the Examiner, additional 35 U.S.C. § 112 and prior art rejections may be readily applied in a subsequent office action
Claim 11 contains trademark/trade names aplidin and celebrex. 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 the chemotherapeutic agent of an antibody drug conjugate and, accordingly, the identification/description is indefinite.
Claims 19 and 25 recite exemplary language that renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. Specifically, the phrase “(optionally selected from…)” renders the claim indefinite in regards to instant claim 19 because it is unclear whether the limitations following the phrase are part of the claimed invention. In regards to instant claim 25, the content in the parentheses, e.g. SEQ ID NOs, is not defining the term preceding it, therefore, rendering the claim indefinite because it is unclear whether the limitations are part of the claimed invention. See MPEP § 2173.05(d).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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 1-8, 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 1-8, 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, 4, and 8; 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 5 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 1-5 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-Xaa-Xaa-Asp wherein Xaa represents any amino acid residue, 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 that are selected from the group consisting of Asp-Xaa-Xaa-Asp, Leu-Xaa-Xaa-Asp, and Val-Xaa-Xaa-Asp, wherein Xaa represents any amino acid residue; 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 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 a C-terminal amino acid residue comprising Asp-Xaa-Xaa-Asp wherein Xaa represents any amino acid residue, 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 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-Xaa-Xaa-Asp wherein Xaa represents any amino acid residue, joined directly to, iii) a therapeutic agent.
Regarding instant claim 6, 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 wherein the caspase-cleavable peptide linker comprises four C-terminal amino acid residues Asp-Xaa-Xaa-Asp wherein Xaa represents any amino acid residue joined directly to, iii) a therapeutic agent as taught by the combined teachings of Kim ‘572 and Kim ‘760 and substitute Xaa with Glu and Val to form the four C-terminal residues Asp-Glu-Val-Asp in the caspase cleavable linker 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 comprising four C-terminal amino acid residues that are selected from the group consisting of Asp-Xaa-Xaa-Asp, Leu-Xaa-Xaa-Asp, and Val-Xaa-Xaa-Asp, wherein Xaa represents any amino acid residue wherein the four C-terminal amino acid residues comprise the amino acid sequence 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 take the anti-doppel ADC comprising: i) a doppel-targeting moiety, joined directly to, ii) a caspase-cleavable peptide linker wherein the caspase-cleavable peptide linker comprises four C-terminal amino acid residues Asp-Xaa-Xaa-Asp wherein Xaa represents any amino acid residue, joined directly to, iii) a therapeutic agent as taught by the combined teachings of Kim ‘572 and Kim ‘760 and substitute Xaa with Glu and Val to form the four C-terminal residues Asp-Glu-Val-Asp in the caspase cleavable peptide linker as taught by Kim ‘572 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 comprising 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 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 cleavable linker wherein the amino acid sequence comprises Lys-Gly-Asp-Glu-Val-Asp as taught by Kim ‘572 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, 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 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 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 have been motivated 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 therapeutic agent to comprise a chemotherapeutic agent wherein the chemotherapeutic agent comprises anthracyclines, doxorubicin, bleomycin, or MMAE as taught by Kim ‘572 to form the instant anti-doppel 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 is a chemotherapeutic agent that comprises anthracyclines, doxorubicin, bleomycin, or MMAE.
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 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 pharmaceutical composition comprising the ADC and a pharmaceutically acceptable carrier wherein the pharmaceutical composition is formulated for intravenous administration as taught by Kim ‘572 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.
Claims 9 and 17 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 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 claims 9 and 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 have been motivated 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 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 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; ii) a toxin, e.g. diphtheria toxin; iii) a radionuclide, e.g. 90Y; and/or iv) a DNA cross-linking agent, e.g. PBD as taught by Lippincott 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 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 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 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 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 to form the instant ADC wherein the instant ADC is 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 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 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.
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.
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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 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 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 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 pharmaceutical composition comprising the ADC and a pharmaceutically acceptable carrier wherein the pharmaceutical composition is formulated for intravenous administration as taught by Kim ‘572 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 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 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.
Conclusion
No claims are allowed.
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/J.H./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643