DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-4, 7, 13, 15, 18-21, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57-58, and 67-68) and the below-listed species in the reply filed on 05/18/2026 is acknowledged.
Elected Species:
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Antibody-drug conjugate corresponding to secondary identifier Ab D-L11C-P25 wherein Ab D is an anti-CD7 antibody and the structure of L11C-P25 is as shown below.
Claim Status
Claims 5-6, 8-12, 14, 16-17, 22, 24-25, 27-30, 32-33, 35-36, 39-43, 47, 49-54, 56, 59-66, 70-88, and 91-95 have been cancelled and claims 1-4, 7, 13, 15, 18-21, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57-58, 67-69, 89-90, and 96 have been amended, as requested in the amendment filed on 03/22/2024. Following the amendment, claims 1-4, 7, 13, 15, 18-21, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57-58, 67-69, 89-90, and 96 are pending in the instant application.
Claims 69, 89-90, and 96 stand as withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, and claims 4, 7, 13, 15, and 18-21 stand as withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species of invention, in the Response filed 05/18/2026, there being no allowable generic or linking claim.
Claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57-58, and 67-68 are under examination in the instant office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57-58, and 67-68 have an effective filing date of November 24, 2020 corresponding to PRO 63/117,763.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/16/2023 and 05/18/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings are objected to because Figures 2 and 8A-B contain text/labels that are blurry and difficult to read. Furthermore, the figure labels for Figures 15-16 do not match the orientation of the figures; Figures 15-16 are in landscape orientation, but the labels identifying the figures are at the bottom of the page in portrait orientation. 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.
Specification
The disclosure is objected to because of the following informalities: there are structures throughout the specification wherein elements of the structure are blurry and difficult to make out. For example, the heteroatoms of the Het1 structures (see Page 13, for example) and the heteroatoms of the G structures (see Page 14, for example).
Appropriate correction is required.
Claim Objections
Claims 1 and 45-46 objected to because of the following informalities: heteroatoms within structures comprised within the recited claims are blurry and very difficult to read. Appropriate correction is required.
Claim 1 is further objected to because of the following informalities: (i) the claim has miscellaneous bullet points throughout the claim (see for example the top of claims Page 8); (ii) there are multiple instances of the typographical error “and :”, which should read “and:” (see, for example, claims Page 8 at the definition of R8); (iii) the definition of B1, B2, B3, and B4 at claims Pages 10 and 18 recite “a C3-C8heterocycloalkyl group, which group can…”, but should read “a C3-C8heterocycloalkyl group, which can…”; (iv) there is a period at the end of the definition of “------” at claims Page 11 which does not designate the end of the claim or an abbreviation; and (v) the definition of R8 at claims Page 16 recites “R’c”, which should read “R’c”. Appropriate correction is required.
Claim 26 is objected to because of the following informalities: the claim lists limitations, wherein the listed limitations are designated by “A.”, “B.”, etc. As such, the claim comprises periods which do not designate the end of a sentence or an abbreviation. Appropriate correction is required.
Claim 46 is further objected to because of the following informalities: (i) there are multiple instances of the typographical error “and :”, which should read “and:” (see, for example, claims Page 81 at the definition of R8); and (ii) the definition of B1, B2, B3, and B4 at claims Pages 83 and 86 recite “a C3-C8heterocycloalkyl group, which group can…”, but should read “a C3-C8heterocycloalkyl group, which can…”. Appropriate correction is required.
Claim Interpretation
With regard to the sequence language of instant claim 58, the following are noted:
The recitation of, for example, “comprising an amino acid sequence of SEQ ID NO:92” is being interpreted as open sequence language, such that a reference sequence meets the limitation when the reference sequence comprises at least two consecutive amino acid residues comprised within SEQ ID NO: 92; a reference sequence may be any truncation and/or comprise mutations relative to SEQ ID NO: 92 so long as the reference sequence comprises at least two consecutive amino acid residues comprised within SEQ ID NO: 92.
The recitation of, for example, “the heavy chain amino acid sequence of SEQ ID NO:143” is being interpreted as closed sequence language, wherein a reference sequence meets the limitation when the reference sequence comprises or consists of an exact match to full-length SEQ ID NO: 143.
The recitation of, for example, “comprising amino acid sequences of SEQ ID NO:39” is being interpreted as open sequence language, such that a reference sequence meets the limitation when the reference sequence comprises at least two consecutive amino acid residues comprised within SEQ ID NO: 39; a reference sequence may be any truncation and/or comprise mutations relative to SEQ ID NO: 39 so long as the reference sequence comprises at least two consecutive amino acid residues comprised within SEQ ID NO: 92.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 58, and 67-68 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.
Regarding claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 58, and 67-68 the phrases “optionally substituted”, “may be substituted”, and/or “substituted” as currently recited throughout the claims render them indefinite because the phrases compound on each other and as such there are thousands of possible structural iterations of the claimed antibody-drug conjugates and it would be unclear to one of ordinary skill in the art which possible iterations are encompassed by the present claims and maintain the desired functions and properties. Thus, one of ordinary skill in art could not reasonably ascertain the metes and bounds of the claims.
Further regarding claims 1 (at claims Pages 10 and 18) and 46 (at claims Pages 83 and 86), the claims recite the limitation "the nitrogen atom" in the definition of B1, B2, B3, and B4. There is insufficient antecedent basis for this limitation in the claim because it is unclear as to what “the nitrogen atom” is intended to refer to; there is no nitrogen atom recited earlier in the definition(s) of B1, B2, B3, and B4 and there are numerous nitrogen atoms throughout the possible structural iterations comprised by the instant claims. Thus, “the nitrogen atom” lacks antecedent basis and is indefinite.
Further regarding claims 23, 26, 34, 37-38, it is noted that claim 23 recites the limitation "the Bcl-xL inhibitor" throughout the claim. There is insufficient antecedent basis for this limitation in the claim because it is unclear if “the Bcl-xL inhibitor” is intended to refer to the Bcl-xL inhibitor of Formula (I) or (II) from claim 1. Thus, “the Bcl-xL inhibitor” lacks antecedent basis and is indefinite; claims 26, 34, and 37-38 are included here as they all depend from claim 23.
Further regarding claim 26, the claim is further considered to be indefinite because it currently reads at claims Page 40 B.(1) “C2-C6 alkyl substituted with 1 to 3, [structures], or C2-C6alkyl substituted with 1 to 2 substituents selected from…” and it is unclear as to what “substituted with 1 to 3” is meant to refer to and include. Thus, one of ordinary skill in art could not reasonably ascertain the metes and bounds of the recited limitation and therefore the claim.
Further regarding claim 38, the claim is further considered to be indefinite because the claim currently reads at line 2 “and/or R is -CH3 or -CH2CH2COOH” and it is unclear as to what “R” is referring to, as none of the claims comprise a structural element designated as “R”. Thus, one of ordinary skill in art could not reasonably ascertain the metes and bounds of the recited limitation and therefore the claim.
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.
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.
Claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57-58, and 67-68 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/018858 A1 (Foreign Patent Document Citation No. 6 on 08/16/2023 IDS; herein after referred to as "Novak") in view of WO 2020/236841 A2 (herein after referred to as "Chen") and non-patent literature by Bremer et. al. (Blood, 2006, 107(7), 2863-2870; herein after referred to as "Bremer").
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Novak teaches 6,7-dihydro-5H-pyrido[2,3-c]pyridazine, 1,2,3,4-tetrahydroquinoline, lH-indole,3,4-dihydro-2H-l,4-benzoxazine, 1H-pyrrolo[2,3-b]pyridin-l-yl, 7H-pyrrolo[2,3-c]pyridazine, 5H,6H,7H,8H,9H-pyridazino[3,4-b]azepine derivatives and related compounds of formula (I) as Bcl-xL protein inhibitors for use as pro-apoptotic agents for treating cancer, autoimmune diseases or immune system diseases (Abstract).
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More specifically, Novak teaches that a compound of formula (I) includes a compound of formula (IA):
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wherein it is noted that Novak formula (IA) is the same as instant formula (II), further wherein the substituents of Het1, A4, A5, R1 Het2, R2, Z1, and R3 are defined the same as in the instant application (see Pages 4-12). Novak further discloses that the structure of formula (IA) includes (Pages 12-13):
With regard to the above structure is noted that:
R1 includes, as defined at Page 5, C1 alkyl (i.e., -CH3)
Z1 includes, as defined at Page 5, a bond
R3 includes, as defined at Page 5, a H
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Het1 includes the structure as indicated on Page 13:
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Het2 includes the structure as indicated on Page 14:
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R6 includes the structure as indicated on Page 16:
R7 includes the structure as indicated on Page 16, wherein R8 represents
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-O-X'2-NR'aR'b and further wherein X’2 includes, as defined at Page 10, a linear C2 alkylene (i.e., -CH2-CH2-), R’a and R’b are independently, as defined at Page 10, a H and a C3 alkyl substituted by one hydroxy group (i.e., -CH2-CH2-CH2-OH), and each of R12 and R13 are, as defined at Page 9, a C1 alkyl (i.e.,
-CH3):
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It is noted that structures above read on a Bcl-xL inhibitor structure as shown below, which corresponds to the instantly elected species of Bcl-xL inhibitor:
Novak teaches pharmaceutical compositions comprising at least one compound of formula (I), as the active ingredient, in combination with one or more pharmaceutically acceptable excipients. Actual dosage levels of the active ingredients in the pharmaceutical compositions of the invention may be varied so as to obtain an amount of the active ingredient which is effective
to achieve the desired therapeutic response for a particular patient, composition, and mode of
administration, without being toxic to the patient (Page 33, Lines 24-27); a suitable daily dose of a compound of the invention will depend upon the factors described above and may range from 0.01 mg to 2.5 g per day in one or more administration(s) (Page 34, Lines 7-8). In particular, the pharmaceutical compositions are interesting for use as pro-apoptotic and/or anti-proliferative agents, particularly, in the treatment of cancers and of auto-immune and immune system diseases (Page 33, Lines 4-8). Treatments envisaged include hematological malignancies and solid tumors, wherein (i) hematological malignancies include myeloma, especially multiple myeloma, lymphoma, especially Non-Hodgkin Lymphoma (NHL) and more especially Diffuse Large B-cell Lymphoma (DLBCL), and leukemia, especially Chronic Lymphocytic Leukemia (CLL), T-cell Acute Lymphoblastic Leukemia (T-ALL), B-cell Acute Lymphoblastic Leukemia (B-ALL) and Acute Myelogenous Leukemia (AML); and (ii) solid tumors include the bladder, brain, breast, uterus, esophagus and liver cancers, colorectal cancer, renal cancer, melanoma, ovarian cancer, prostate cancer, pancreatic cancer and lung cancer, especially non-small-cell lung cancer and small-cell lung cancer (Page 32, Lines 1-10). It is further noted that Novak teaches that the compounds of the invention may be linked to monoclonal antibodies to make antibody drug conjugates (ADCs); the monoclonal antibody of an ADC selectively binds to a target antigen of a cell (e.g., cancer cell) and releases the drug into the cell, wherein ADCs have therapeutic potential because they combine the specificity of the antibody and the cytotoxic potential of the drug (Page 34, Lines 17-26). Novak further identifies that developing ADCs as therapeutic agents has thus far met with limited success owing to a variety of factors such as unfavorable toxicity profiles, low efficacies and poor pharmacological parameters; accordingly, there is still a need for new ADCs that overcome these problems and can selectively deliver Bcl-xL to target cancer cells (Id.).
However, it is noted that Novak does not explicitly teach an ADC embodiment comprising a linker L that covalently attaches an antibody to the Bcl-xL inhibitors. This deficiency is remedied by Chen.
Chen provides linkers, linker-drug groups, and ADCs comprising hydrophilic groups (Abstract). Chen indicates that one aspect in the design of antibody drug conjugates (ADCs) is the design of the chemical linker, which links the drug moiety to the targeting moiety; typically, an ADC uses a hydrophobic drug moiety, however when such drug moieties are used in combination with a relatively hydrophobic linker, solubility issues can arise which can affect the biocompatibility and pharmaceutical efficacy of the ADC (Page 1, Lines 10-14). Linker strategies have been reported to attempt to overcome these challenges, in particular the design of hydrophilic linkers incorporating polyethylene glycol, but there remains a need for antibody drug conjugate formats that allow for the targeted delivery of hydrophobic drugs with improved pharmacokinetic and pharmacodynamic properties (Page 1, Lines 15-25). The invention provides linkers for the use in improving the solubility of antibody drug conjugate (ADC) in which the ADC comprises one or more hydrophobic drug compounds, wherein the linkers comprise one or more hydrophilic groups (Page 1, Lines 32-34). Generally, the drug-linkers of Chen are of Formula (I) as shown at Page 2:
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A more specific drug-linker falling under Formula (I) is that of Formula (II) at Page 3:
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It is specifically noted that Chen indicates that ADCs comprising linkers and/or drug-linkers of the invention are of Formula (IV) at Page 4:
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In Embodiment 23, Chen discloses the drug-linker compound shown below, wherein the drug is MMAE:
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It is specifically noted that the linker portion of the above-provided drug-linker structure wherein Xa is -CH2-, t = 21, and R is -CH2CH2C(=O)OH corresponds to the instantly elected linker structure corresponding to instant identifier L11C:
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wherein the * indicates the point of connection to a drug (e.g., a nitrogen- or oxygen-containing drug wherein attachment is via the N or O atom of the drug) and wherein the maleimide moiety is the reactive group where the antibody will be conjugated. Thus, Chen teaches the instantly elected linker and indicates its use in ADCs with nitrogen-containing drugs (i.e., hydrophobic drugs) in order to improve solubility and pharmacokinetic properties of such ADCs.
Thus, the combination of Novak and Chen suggest an ADC comprising (i) a Bcl-xL inhibitor (i.e., a nitrogen-containing drug with unfavorable pharmacological parameters in ADCs) and (ii) a linker for covalent attachment to an antibody, wherein said linker endows favorable properties on the ADC; such an ADC comprising the structure below:
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However, neither Novak nor Chen teach embodiments wherein an antibody of an ADC is an anti-CD7 antibody. This deficiency is remedied by Bremer.
Bremer teaches that human CD7 is a lineage-specific antigen that is highly expressed in
patients with acute T-cell leukemia and in approximately 10% of patients with acute myeloid leukemia; human CD7 has been used for the targeted delivery of several monoclonal antibody (mAb) toxin conjugates in both preclinical studies and clinical trials (Page 2864, Column 1, First Partial Paragraph). The study of Bremer reports on a novel homotrimeric sFasL fusion protein,
designated scFvCD7:sFasL, with enhanced and leukemia-restricted activity toward T-cell acute lymphoblastic leukemia (T-ALL) cell lines and patient-derived T-ALL, peripheral T-cell
lymphoma (PTCL), and CD7-positive acute myeloid lymphoma (AML) cancer cells; the study provides evidence that homotrimeric scFvCD7:sFasL is bioactive only after specific binding to cell surface–expressed CD7 with no toxicity toward CD7-negative cells and only moderate activity toward interleukin-2 (IL-2)/CD3 activated CD7-positive T cells (Page 2864, Column 1, First Full Paragraph). Thus, Bremer teaches that anti-CD7 antibodies (e.g., monoclonal antibodies and/or scFv fragments) have been successfully utilized for the specific, targeted delivery of therapeutic agents in cases of hematological malignancies such as T-ALL and CD7-positive AML.
In the test of whether it is “obvious to try” there must be:
(1) a finding in the art at the time of filing of the invention that there had been a recognized problem or need in the art;
(2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem;
(3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the Bcl-xL inhibitor antibody-drug conjugates suggested by Novak such that they comprise a hydrophilic linker of Chen and an anti-CD7 antibody as suggested by Bremer. One would have been motivated to arrive at such an antibody-drug conjugate because (i) Novak discloses Bcl-xL inhibitor compounds, antibody-drug conjugates comprising cancer/tumor specific antibodies for the targeted treatment of cancers (including T-ALL and AML), and pharmaceutical compositions thereof wherein Novak further identifies that there is a need for Bcl-xL inhibitor-based antibody-drug conjugates that have more desirable pharmacokinetic properties; (ii) Chen teaches that the hydrophilic linkers of the invention are suitable for generally hydrophobic drugs/agents/payloads because the linkers improve critical properties including solubility and efficacy while maintaining biocompatibility and being cleavable under specific conditions for targeted delivery; and (iii) Bremer teaches that anti-CD7 antibodies (e.g., monoclonal antibodies and/or scFv fragments) have been successfully utilized for the specific, targeted delivery of therapeutic agents in cases of hematological malignancies such as T-ALL and CD7-positive AML. One of ordinary skill in the art would have a reasonable expectation of success because Novak suggests Bcl-xL inhibitors of the invention being incorporated into antibody-drug conjugates for the treatment of, for example, hematological cancers; Chen provides specific linkers that address the need of improved pharmacokinetic properties identified by Novak, and Bremer teaches that anti-CD7 antibodies have been used in therapeutic approaches to treating hematological cancers wherein the anti-CD7 antibodies have been conjugated to various therapeutic agents for targeted delivery.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57, and 67-68 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 24, 27, 31-32, 35, 38-39, 44, 47, 51-52, 56, 58, and 91-92 of copending Application No. 18/866,134 (first reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
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First reference application claim 1 is drawn to an antibody-drug conjugate of Formula (1), corresponding to Ab-(L-D)p wherein, generally: Ab is an anti-Met antibody, L is a linker that covalently attached Ab to D, p is an integer from 1 to 16, and D is a Bcl-xL inhibitor of, for example, Formula (II):
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It is specifically noted that first reference application Formula (II) is identical to instant Formula (II) as defined in instant claim 1. First reference application claim 4 further limits the linker L, wherein (i) L comprises an attachment group, at least one bridging spacer group, and at least one cleavable group, or (ii) L comprises an attachment group, at least one bridging spacer group, a peptide group, and at least one cleavable group. First reference application claim 24 further limits the structure of -(L-D), wherein -(L-D) is of, for example, formula (C) or formula (D):
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It is specifically noted that first reference application formula (C) and formula (D) are identical to instant formulas (C) and (D), respectively, as defined in instant claim 23. First reference application claims 27, 31-32, 35, and 38-39 all further limit first reference application claim 24 such that -(L-D) may be, for example, the structure shown below:
First reference application claim 44 limits the antibody-drug conjugate of reference application claim 1 such that D comprises a compound of Formula (II), as shown above. First reference application claims 47, 51-52, 56, and 58 also further limit the antibody-drug conjugate of first reference application claim 1, such that the exact D and -(L-D) structures are specified; it is specifically noted that the fully-provided structures of D and -(L-D) of first reference application claims 56 and 58, respectively, are identical to those of instant claims 55 and 57, respectively. Notably, first reference application claim 58 includes an -(L-D) designated as, for example, L11C-P25:
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which is identical to instant -(L-D) designated as L11C-P25 of instant claim 57. First reference application claim 91 is drawn to a composition comprising multiple copies of the antibody-drug conjugate of claim 1, wherein the average p of the antibody-drug conjugates in the composition is from about 2 to about 16. First reference application claim 92 is drawn to a pharmaceutical composition comprising the antibody-drug conjugate of claim 1, and a pharmaceutically acceptable carrier. Thus, the claims of the first reference application read directly on instant claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57, and 67-68.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 58 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 24, 27, 31-32, 35, 38, 39, 44, 47, 51-52, 56, 58, and 91-92 of copending Application No. 18/866,134 (first reference application), as applied to claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57, and 67-68 above, and in further view of first reference application claim 93 and Bremer et. al. (Blood, 2006, 107(7), 2863-2870; herein after referred to as "Bremer").
Claim 93 of the first reference application is drawn to a method of (a) treating a subject having or suspected of having a cancer, (b) reducing or inhibiting the growth of a tumor in a subject, (c) reducing or inhibiting a hematological cancer in a subject, or (d) reducing or slowing the expansion of a cancer cell population in a subject, comprising administering to the subject a therapeutically effective amount of the antibody-drug conjugate of claim 1.
However, with respect to the instantly elected species, it is noted that the first reference application does not claim an antibody-drug conjugate wherein the antibody is an anti-CD7 antibody. This deficiency is remedied by Bremer.
Bremer teaches that human CD7 is a lineage-specific antigen that is highly expressed in
patients with acute T-cell leukemia and in approximately 10% of patients with acute myeloid leukemia; human CD7 has been used for the targeted delivery of several monoclonal antibody (mAb) toxin conjugates in both preclinical studies and clinical trials (Page 2864, Column 1, First Partial Paragraph). The study of Bremer reports on a novel homotrimeric sFasL fusion protein,
designated scFvCD7:sFasL, with enhanced and leukemia-restricted activity toward T-cell acute lymphoblastic leukemia (T-ALL) cell lines and patient-derived T-ALL, peripheral T-cell
lymphoma (PTCL), and CD7-positive acute myeloid lymphoma (AML) cancer cells; the study provides evidence that homotrimeric scFvCD7:sFasL is bioactive only after specific binding to cell surface–expressed CD7 with no toxicity toward CD7-negative cells and only moderate activity toward interleukin-2 (IL-2)/CD3 activated CD7-positive T cells (Page 2864, Column 1, First Full Paragraph). Thus, Bremer teaches that anti-CD7 antibodies (e.g., monoclonal antibodies and/or scFv fragments) have been successfully utilized for the specific, targeted delivery of therapeutic agents in cases of hematological malignancies such as T-ALL and CD7-positive AML.
In the test of whether it is “obvious to try” there must be:
(1) a finding in the art at the time of filing of the invention that there had been a recognized problem or need in the art;
(2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem;
(3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the Bcl-xL inhibitor antibody-drug conjugates claimed by the first reference application such that they comprise an anti-CD7 antibody, as suggested by Bremer. One would have been motivated to arrive at such an antibody-drug conjugate because the first reference application claims antibody-drug conjugates comprising a cancer/tumor specific antibody (i.e., anti-Met antibody) for the treatment of hematological cancers (including T-ALL and AML), and pharmaceutical compositions thereof and Bremer teaches that anti-CD7 antibodies (e.g., monoclonal antibodies and/or scFv fragments) have been successfully utilized for the specific, targeted delivery of therapeutic agents in cases of hematological malignancies such as T-ALL and CD7-positive AML. One of ordinary skill in the art would have a reasonable expectation of success because claimed the antibody-drug conjugates of the first reference application are claimed as being useful in the treatment of, for example, hematological cancers, and Bremer specifically teaches that anti-CD7 antibodies have been used in therapeutic approaches to treating hematological cancers wherein the anti-CD7 antibodies have been conjugated to various therapeutic agents for targeted delivery; relacing the anti-Met antibody of the first reference application with an anti-CD7 antibody would still reasonably be expected to specifically target and treat hematological cancers.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57, and 67-68 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 23, 26, 30-31, 34, 37-38, 41, 50-51, 55, 57, and 64-65 of copending Application No. 18/866,144 (second reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
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Second reference application claim 1 is drawn to an antibody-drug conjugate of Formula (1), corresponding to Ab-(L-D)p wherein, generally: Ab is an anti-EphA2 antibody, L is a linker that covalently attached Ab to D, p is an integer from 1 to 16, and D is a Bcl-xL inhibitor of, for example, Formula (II):
It is specifically noted that second reference application Formula (II) is identical to instant Formula (II) as defined in instant claim 1. Second reference application claim 2 is drawn to the antibody-drug conjugate of claim 1, wherein p is an integer from 1 to 6, or 2 to 4, or p is 2 or 4; or p is determined by liquid chromatography-mass spectrometry. Second reference application claim 3 further limits the linker L, wherein (i) L comprises an attachment group, at least one bridging spacer group, and at least one cleavable group, or (ii) L comprises an attachment group, at least one bridging spacer group, a peptide group, and at least one cleavable group. Second reference application claim 23 further limits the structure of -(L-D), wherein -(L-D) is of, for
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example, formula (C) or formula (D):
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It is specifically noted that second reference application formula (C) and formula (D) are identical to instant formulas (C) and (D), respectively, as defined in instant claim 23. Second reference application claims 26, 30-31, 34, and 37-38 all further limit second reference application claim 23 such that -(L-D) may be, for example, the structure shown below:
Second reference application claim 43 limits the antibody-drug conjugate of second reference application claim 1 such that D comprises a compound of Formula (II), as shown above. Second reference application claims 46, 50-51, 55, and 57 also further limit the antibody-drug conjugate of second reference application claim 1, such that the exact D and -(L-D) structures are specified; it is specifically noted that the fully-provided structures of D and -(L-D) of second reference application claims 55 and 57, respectively, are identical to those of instant claims 55 and 57, respectively. Notably, second reference application claim 57 includes an -(L-D) designated as, for example, L11C-P25:
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which is identical to instant -(L-D) designated as L11C-P25 of instant claim 57. Second reference application claim 64 is drawn to a composition comprising multiple copies of the antibody-drug conjugate of claim 1, wherein the average p of the antibody-drug conjugates in the composition is from about 2 to about 16. Second reference application claim 65 is drawn to a pharmaceutical composition comprising the antibody-drug conjugate of claim 1, and a pharmaceutically acceptable carrier. Thus, the claims of the second reference application read directly on instant claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57, and 67-68.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 58 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 23, 26, 30-31, 34, 37-38, 41, 50-51, 55, 57, and 64-65 of copending Application No. 18/866,144 (second reference application), as applied to claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57, and 67-68 above, and in further view of second reference application claim 66 and Bremer et. al. (Blood, 2006, 107(7), 2863-2870; herein after referred to as "Bremer").
Claim 66 of the second reference application is drawn to a method of (a) treating a subject having or suspected of having a cancer, (b) reducing or inhibiting the growth of a tumor in a subject, (c) reducing or inhibiting a hematological cancer in a subject, or (d) reducing or slowing the expansion of a cancer cell population in a subject, comprising administering to the subject a therapeutically effective amount of the antibody-drug conjugate of claim 1.
However, with respect to the instantly elected species, it is noted that the second reference application does not claim an antibody-drug conjugate wherein the antibody is an anti-CD7 antibody. This deficiency is remedied by Bremer.
Bremer teaches that human CD7 is a lineage-specific antigen that is highly expressed in
patients with acute T-cell leukemia and in approximately 10% of patients with acute myeloid leukemia; human CD7 has been used for the targeted delivery of several monoclonal antibody (mAb) toxin conjugates in both preclinical studies and clinical trials (Page 2864, Column 1, First Partial Paragraph). The study of Bremer reports on a novel homotrimeric sFasL fusion protein,
designated scFvCD7:sFasL, with enhanced and leukemia-restricted activity toward T-cell acute lymphoblastic leukemia (T-ALL) cell lines and patient-derived T-ALL, peripheral T-cell
lymphoma (PTCL), and CD7-positive acute myeloid lymphoma (AML) cancer cells; the study provides evidence that homotrimeric scFvCD7:sFasL is bioactive only after specific binding to cell surface–expressed CD7 with no toxicity toward CD7-negative cells and only moderate activity toward interleukin-2 (IL-2)/CD3 activated CD7-positive T cells (Page 2864, Column 1, First Full Paragraph). Thus, Bremer teaches that anti-CD7 antibodies (e.g., monoclonal antibodies and/or scFv fragments) have been successfully utilized for the specific, targeted delivery of therapeutic agents in cases of hematological malignancies such as T-ALL and CD7-positive AML.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the Bcl-xL inhibitor antibody-drug conjugates claimed by the second reference application such that they comprise an anti-CD7 antibody, as suggested by Bremer. One would have been motivated to arrive at such an antibody-drug conjugate because the second reference application claims antibody-drug conjugates comprising a cancer/tumor specific antibody (i.e., anti-EphA2 antibody) for the treatment of hematological cancers (including T-ALL and AML), and pharmaceutical compositions thereof and Bremer teaches that anti-CD7 antibodies (e.g., monoclonal antibodies and/or scFv fragments) have been successfully utilized for the specific, targeted delivery of therapeutic agents in cases of hematological malignancies such as T-ALL and CD7-positive AML. One of ordinary skill in the art would have a reasonable expectation of success because claimed the antibody-drug conjugates of the second reference application are claimed as being useful in the treatment of, for example, hematological cancers, and Bremer specifically teaches that anti-CD7 antibodies have been used in therapeutic approaches to treating hematological cancers wherein the anti-CD7 antibodies have been conjugated to various therapeutic agents for targeted delivery; relacing the anti-EphA2 antibody of the second reference application with an anti-CD7 antibody would still reasonably be expected to specifically target and treat hematological cancers.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1-4, 7, 13, 15, 18-21, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57-58, 67-69, 89-90, and 96 are pending. Claims 4, 7, 13, 15, 18-21, 69, 89-90, and 96 are withdrawn. Claims 1-3, 23, 26, 31, 34, 37-38, 44-46, 48, 55, 57-58, and 67-68 are rejected. No claims are allowed.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
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