DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-18 are under consideration.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/27/2026 has been entered.
Claim Objections/Rejections Withdrawn
The 35 USC 112(d) rejection of claim 7 has been withdrawn in view of claim amendment
Rejections Maintained/New Rejections Necessitated by Amendment
Improper Markush Grouping
Claims 1-6 and 8-18 are rejected on the basis that claims 1, 17 and 18 contain improper Markush groupings of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
Claim 1
The Markush grouping of agents recited for variable T in claim 1 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Claim 1 is directed to T moieties selected from the Markush group of cell-binding agents recited in instant claim 1. The instant Specification teaches that the instant claimed conjugate is intended for use in the treatment of cancers, wherein the tubulysin component of the instant claimed conjugate acts as a cytotoxic agent to kill the cancer cells and with the cell binding agent directing the conjugate to the cancer cells, minimizing off-target toxicity (Specification, p 1, line 15--- p 4, line 29).
The cell-binding recited in claim 1 are not recognized members of the same recognized physical or chemical class or the same art-recognized class and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Additionally, the cell-binding agents recited in claim 1 do not possess a common use because the species recited in claim 1 have highly variant intra-group functionalities. The alternatives do not possess a single share a single structural similarity because of the fact that the alternatives belong to highly variant structural and functional genera. For example, a monoclonal antibody and a “a small molecule attached on albumin, a polymer, a liposome a nanoparticle, a vesicle or a viral capsid” are listed as alternatives despite the monoclonal antibody binding to cells based on antibody-antigen interaction and the small molecule attached to albumin, a polymer, etc… would have to bind to cells based on interaction small molecule ligand-protein interaction between the undefined small molecule and the undefined cellular target.
Claim 17
The Markush grouping of chemotherapeutic agents recited in claim 17 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Claim 17 is directed to pharmaceutical compositions comprising the instant claimed conjugate and further comprising a chemotherapeutic agent selected from the Markush group of chemotherapeutic agents recited in instant claim 17. The instant Specification teaches that the instant claimed conjugate is intended for use in the treatment of cancers, wherein the tubulysin component of the instant claimed conjugate acts as a cytotoxic agent to kill the cancer cells and with the cell binding agent directing the conjugate to the cancer cells, minimizing off-target toxicity (Specification, p 1, line 15--- p 4, line 29).
The additional “chemotherapeutic agents” recited in claim 17 are not recognized members of the same recognized physical or chemical class or the same art-recognized class and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Additionally, the additional “chemotherapeutic agents” recited in claim 17 do not possess a common use because the species recited in claim 17 have highly variant intra-group functionalities (e.g., some species are antibiotics, some species are antivirals, some species are hormone therapeutics, etc…). The alternatives do not possess a single share a single structural similarity because of the fact that the alternatives belong to highly variant structural genera. For example, cyclophosphamide and colistin are listed as alternatives despite cyclophosphamide being a small molecule DNA alkylating agent and colistin being a peptidic antibiotic.
Claim 18
The Markush grouping of agents recited in claim 18 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Claim 18 is directed to pharmaceutical compositions comprising the instant claimed conjugate and further comprising a agent selected from the Markush group of chemotherapeutic agents recited in instant claim 18. The instant Specification teaches that the instant claimed conjugate is intended for use in the treatment of cancers, wherein the tubulysin component of the instant claimed conjugate acts as a cytotoxic agent to kill the cancer cells and with the cell binding agent directing the conjugate to the cancer cells, minimizing off-target toxicity (Specification, p 1, line 15--- p 4, line 29).
The additional agents recited in claim 18 are not recognized members of the same recognized physical or chemical class or the same art-recognized class and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Additionally, the additional agents recited in claim 18 do not possess a common use because the species recited in claim 18 have highly variant intra-group functionalities. The alternatives do not possess a single share a single structural similarity because of the fact that the alternatives belong to highly variant structural and functional genera. For example, trastuzumab and lisdexamphetamine are listed as alternatives despite trastuzumab being a HER2-targeting monoclonal antibody administered in methods of treating HER2+ cancer and lisdexamphetamine is a small molecule stimulant drug used to treat attention deficit disorder.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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 1-6 and 8-18 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 1
The meets and bounds of the base claim 1 are vague and indefinite due to the prolix nature of the claim language. How some of different variables are connected to each other is undefined, the ‘how’ being not relating to method, rather definition of functionalities related to linking. The large number of variables also include vaguely defined groups such as ‘natural or unnatural amino acid, and optional substituents on generically recited substituents such as aryl, heteroaryl rendering the scope of the claim vague. Many of the variables moieties defined are directed to multiple moieties with conflicting, incompatible valencies. Consider for example variable R16, recited in instant claim 1. Instant claim 1 recites one variable moiety N=R16, which carries the possible of impossible valencies such as Na+, K+, Li+, and N+(R1)(R2)(R3)(R4), and none of these moieties are capable of forming a double bond to N. According to MPEP guidelines regarding such situations (2173.05) Examiners should reject claims as prolix only when they contain such long recitations or unimportant details that the scope of the claimed invention is rendered indefinite thereby. Claims are rejected as prolix when they contain long recitations that the metes and bounds of the claimed subject matter cannot be determined. Similarly, the prolix nature of the permissible moieties of the claimed structure defies commonsense. Further incompatible substituents are recited in for the many of the variables. An example would be the definitions of X1 and X2 in the definition of Q1 and Q2:
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X1 and X2 are both permitted to be +NH(R1), which is not possible because a quaternary amine cannot have a hydrogen in it. This presents one of many ‘impossible substituent’ situations . This ‘incompatibility’ is not an enablement issue, see below.
An argument that all this relate to (scope of) enablement issue would not be persuasive, because if a substituent is impossible, the claim can properly be rejected under 35 USC 112 (a) or (b): A compound with an impossible substituent clearly cannot be made, and hence a 112(a) rejection is proper. Alternatively, if it is impossible, then it is not correct. An exhaustive patent search respecting all of the recited permissible moieties for the formulae recited in base 1 could not be completed. Dependent claims do not solve all the problems of the base claim. As such they are rejected as well.
Claim 1 recites a tubulysin analog of Formula (II)
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Claim 1 recites that the dashed lines in the figure above indicate “a linkage site that links to W independently, D links to W or L1 or L2 when absent….. via one or two of ------ of R1, R2, R7, R8, R9, R12, R13, and R14”. All of R1, R2, R7, R8, R9, R12, R13 and R14 are attached to dashed lines. Claim 1 recites that the linkage to W is selected from one or two of the dashed lines, allowing for the possibility of multiple linkages to W via multiple R groups but it is also not possible for this many of these R groups to simultaneously form linkages to W and still also comprise the recited moieties. Also, it not clear what the of R1, R2, R7, R8, R9, R12, R13 and R14 groups link to via their respective dashed lines when they do not link to W.
Claim 13
Claim 13 recites that the surfactant is select from a list including “or isostearyl ethylimodium ethosulfate, polyethyl glycol, polypropyl glycol and copolymers of ethylene and propylene glycol. It is not clear how the surfactant can be both isostearyl ethylimodium ethosulfate AND copolymers of ethylene and propylene oxide at the same time.
Additionally, claim 13 contains Markush groups comprising multiple semicolon-delineated subgroupings, with the subgroupings being comma-delineated and having an “or” conjunction. For example: with respect to the buffer salt, claim 13 recites “….gluconic acid, carbonic acid, tartaric acid, succinic acid, acetic acid or phthalic acid; Tris or tromethamine hydrochloride, phosphate or sulfate…” . In this specific example, it is unclear if the buffer salt is to be selected from the gluconic acid, carbonic acid, etc… grouping or the Tris or tromethyalmine, etc…. grouping, rendering the metes and bounds of the claim unclear and therefore indefinite.
Claim 17
Claim 17 recites lists of Markush alternatives selected from groups “comprising” the listed elements. For example, claim 17 (1)(b) recites “taxoids: comprising paclitaxel, docetaxel and their analogs” and claim 17 (1)(d) recites “DHFR inhibitors: comprising methotrexate, trimetrexate, denopterin, pteroprerin, aminopterin or folic acid analogues”. A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022) (See MPEP 2173.05).
Note: in addition to 17 (1)(b) and (1)(d), this improper open-ended language can be found in (4), (3) and (1)(a)
Additionally, claim 17 contains Markush groups comprising multiple semicolon-delineated subgroupings, with the subgroupings being comma-delineated and having an “or” conjunction. For example: with respect alkylating agents (1)(a), claim 17 recites “….alkylsulphonates:; triazines or decacarbazine; platinum containing compounds; comprising carboplatin, cisplatin and oxaliplatin;: Tris or tromethamine hydrochloride, phosphate or sulfate…” . In this specific example, it is unclear if the buffer salt is to be selected from the triazines or decacarbazine, etc…… grouping or the carboplatin, cisplatin, etc… grouping, rendering the metes and bounds of the claim unclear and therefore indefinite.
Response to Arguments
Applicant's arguments filed 6/15/2026 have been fully considered but they are not persuasive.
Applicant argues that the amendment to claim 1 specifying that amending claim 1 to read “a linkage site that links…. one or two of…” instead of “a linkage site that links one or more of…” is sufficient to remedy the indefiniteness of claim 1. This is not the case because the claim amendments do not address any of the issues at the heart of the rejection. In formula (III), D forms a bond to a single moiety—W. The language of claim then contradicts this by saying that D may have more than one bond to W. Additionally, there are some permissible moieties that are not chemically suitable for forming a bond to W. For example, R1 is permitted to be hydrogen. However, R1 is also one of the sites where D may form a bond with W, but this is impossible because hydrogen would have to form two bonds—one with Y1 and one with W. Additionally, it is still not clear what the R1, R2, R7, R8, R9, R10, R11, R12, R13 and R14 link to when they do not link to W.
Claim 5
Claim 5 is dependent on claim 1 and recites that the variables W, L1, L2, V1 and V2 (all recited in claim 1) are independently composed of one or more of the linker structures recited in instant claim 5. Several of the structures of claim 5 are reproduced below, with wavy lines indicating points of attachment to the rest of the conjugate:
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Note that the linker components above are permitted to comprise anywhere from 2 to 5 points of attachment to the rest of the conjugate. It is logically impossible for these components to both comprise varying numbers of points of attachment to the rest of the conjugate and also be interchangeable linker components permissible at W, L1, L2, V1 and V2 and, as such, the metes and bounds of the claim are unclear.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-6 and 8-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claim 1 recites the limitation that element D of the side chain linked conjugate is a “tubulysin analog”.
In the study of drugs, “analogue” is taken to mean a molecule that shares structural and pharmacological properties with the original compound (Wermuth, C., Drug Discovery Today 2006 Apr; 11(7-8):348-54). Neither the Claims nor the Specification teach the core structure of tubulysin within the molecule that is required for the invention’s essential biological activities and which structural elements are free to be modified in order to arrive at an analog. The claims are directed to a D moiety that is a tubulysin analog of the highly general formula (II):
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….followed by one and a half pages of text defining permissible chemical moieties for the variable groups of general formula (II), often in terms of variable groups nested within variable groups and also comprising permissible moieties of vastly differing chemical properties, making up an incredibly large and diverse genus of distinct chemical species, with each being claimed to possess the required function of acting as a tubulysin analog. MPEP 2163 says that the written description requirement may be satisfied in two ways in structure/function situations: 1) by disclosure of a “representative number of species” that are adequately described, adequately represent the genus and reflect the variation within the genus or 2) establishment of structure/function correlation. The instant Specification does disclose a total of 44 species of ADC with distinct structures and with the demonstrating their capability of acting as a tubulysin analog by killing NCI-N87 cells, with these species being disclosed in Table 1 (Specification, p 251- 258). However, the Specification discloses 44 species of ADC, with many of these ADCs sharing the same D moiety (e.g., 444, 455, 467, 474, 480, 486 and 493, all of which are found on p 252) and, as such, the number of species disclosed possessing the required function of acting a tubulysin analog is insufficient to be representative of the astronomically large and highly diverse genus of chemically distinct species encompassed by D of claim 1. The instant disclosure also does not establish structure/function correlation sufficient to allow a skilled artisan to envision which of the astronomically large and highly diverse genus of chemical species encompassed by D of claim 1 would be capable of performing the required function of acting as a tubulysin analog.
Minor modifications to a molecule can affect the molecule’s pharmacological activity drastically. For example, the drugs amphetamine and methamphetamine differ by one methyl group. It has been demonstrated in the literature that this single methyl group is capable of demonstrably altering the effect of the drug on dopamine transporters in vitro and in vivo (Goodwin, et al. J. Biol. Chem. 2009 Jan; 284(5): 2979-2989).
By claiming tubulysin along with the word “analog” but not including a written description of what modifications to the molecule’s structure may be performed to create such an analog that retains the molecule’s claimed function, the inventors fail to satisfy the written description requirement with respect to the key characteristics and structures of the invention and demonstrate that they were not in possession of the invention at the time of filing.
Claims 1-6 and 8-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claims 1, 8, 10 and 11 are directed to conjugates comprising a “cell binding agent”. As such, the claims are directed to a binding moiety capable of performing the recited function of binding to a cell. Claim 1 recites a very long list of highly variant genera of molecules capable of performing the required function of binding to a cell. Claim 1 is directed to cell binding agent genera including, but not limited to: antibodies, adnectins that mimic antibodies, lymphokines, liposomes, polymers and dendrimers.
Claim 8 is dependent on claim 1 and further limits claim 1 by reciting slightly narrower genera for the claimed moiety capable of performing the required function of binding a cell. The slightly narrower genera of cell binding agents recited in claim 8 include, but are not limited to full length antibodies, resurfaced antibodies, fusion proteins, “large molecular weight proteins”, glutamic acid derivatives, EGF receptors, a “nanoparticle drug carrier” and “integrin receptors’ [sic] and their receptor subtypes’ [sic] agonists and its derivatives”. Please note that class “D” of claim 8, which recites small molecule cell binding agents, is the only recitation of cell binding agents having known and definite structure (e.g., LB50, LB10, etc….) in the claims.
Claim 10 is dependent on claim 1 and further limits claim 1 by reciting cell and/or antigenic targets that the cell binding agent of claim 1 targets. Claim 10 is directed to cell binding agents capable of binding to various cell types (e.g., tumor cells, myeloid cells, activated T cells and parasite-infected cells). Claim 10 is also directed to cell binding agents that can bind a cell expressing any one of the four pages of antigens/receptors recited in claim 10 (e.g., CD1, CD1a, CD64, etc…). Claim 11 is dependent on claim 10 and further limits claim 11 by reciting a list of specific tumor tissue types (e.g., lymphoma cells, squamous cancer cells, etc…) as well as “cells that grow and divide at an unregulated, quickened pace to cause cancers”. As such, claims 10 and 11further limit the recited function of the cell binding agent of claim 1 without providing any additional structure that would allow the cell binding agent to perform these functions.
MPEP 2163 says that the written description requirement may be satisfied in two ways in structure/function situations: 1) by disclosure of a “representative number of species” that are adequately described, adequately represent the genus and reflect the variation within the genus or 2) establishment of structure/function correlation.
The instant Specification discusses cell binding agents at p 107, line 6 – p 132, line 8. The Specification does disclose cell binding agents that are antibodies (Specification, p 108, line 5- p 119, line 14), cell binding agents that are ligand or receptor agonists (Specification, p 119, line 15- p 122, line 2), cell binding agents that are non-immunoglobin protein scaffolds (Specification, p 122, line 3- p 122, line 23) and cell binding agents that are small molecules (Specification, p 122, line 24- p 132, line 8), however all of these “disclosures” are little more than long recitations of highly variant genera of molecule types that comprise some species capable of performing the required function of binding a cell. The species disclosed in the instant Specification do not constitute a disclosure of adequately described species that is adequately representative of the claimed genus of cell binding agents simply due to the absurdly large nature of the claimed genus. For example, claim 11 is directed to cell binding agents that bind “cells that grow and divide at an unregulated, quickened pace to cause cancers”. This effectively encompasses all cancerous and precancerous cells and the species disclosed are not representative of such a large genus.
The instant disclosure also does not establish structure/function correlation sufficient to allow a skilled artisan to envision which of the astronomically large and highly diverse genus of chemical and biochemical species encompassed by the instant claims would be capable of performing the required function of binding a cell as described in instant claims 1, 8, 10 and 11.
Ahmad (Ahmad, et al., Adv Med, Den and Health Sci, 2021 4(4):37) teaches on the subject of molecular docking, which is a method of predicting the binding between a ligand and a receptor, which is often a protein with a known 3D structure, by identifying appropriate positions of the molecules with each other when bound together for forming a stable complex (Ahmad, Abstract). Ahmad teaches that there are multiple general methods of docking, which make differing assumptions about the protein and the ligand and that these include: 1) the rigid ligand/rigid receptor approach, 2) the flexible ligand/rigid receptor approach, 3) the flexible ligand/flexible receptor approach and 4) the local move Monte Carlo approach (Ahmad, p 38, ¶ 4 – p 39, ¶ 2) Ahmad teaches that applications of molecular docking have included the identification of compounds capable of binding to and inhibiting the SARS-CoV-2 protease Mpro (Ahmad, p 41, ¶3).
With respect to structure-function correlation, the teachings of Ahmad show that, at the time of filing, even predicting whether or not any given ligand will bind to any given protein requires knowing the structure of the protein, knowing the structure of the ligand and performing molecular docking calculations in order to predict whether or not the given ligand is likely to bind to the protein. This means that, at the time of filing, it was possible to a skilled artisan to use techniques such as molecular docking to determine if any given candidate cell binding agents is likely to bind to any of the recited cell or antigen types, these techniques to not provide sufficient structure-function correlation to permit a skilled artisan to start with any of the instant claimed cell binding agent genera and envision the required, unrecited structure that is required to perform the required function of binding a cell as described in claims 1, 8, 10 and 11. There is nothing in the instant Specification to supplant this notion. Because the species disclosed are insufficient to be considered representative of any of the genera encompassed in the rejected claims coupled with the lack of established structure/function correlation, claims 1-6 and 8-18 lack written description and Applicant was not in possession of the invention as claimed.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 4, 7-8, and 10-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burke (Burke, et al., WO 2017/096311 A1; Published 06/08/2017; Priority to 12/4/2015 by way of US 62/263,578, of record).
Burke discloses drug-linker-crosslinker moiety 95 of Burke (Burke, ¶ 1298), which was conjugated to the anti-CD30 antibody cAC10, with the resultant ADC having an IC50 of 0.8 ng/mL against L540cy Hodgkin’s lymphoma cells (Burke, ¶ 1441):
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Regarding claim 1, the ADC of Burke fully satisfies the limitations of Formula III of claim 1 when T is the anti-cAC10 antibody, V2, L2, and Q2 are absent, the crosslinker is V1, the peptide moiety is L1, the PEG moiety is Q1, the PAB moiety is W, and the tubulysin of Burke is D (with the heterocyclic ring being formed when R2 and R4 come together to form the heterocycloalkyl ring and wherein R1 is absent, thus making the N link directly to W). Regarding claim 4, the tubulysin of Burke reads on tubulysin I-51 (presumed to be unconjugated tubulysin). Regarding claim 8, antibody cAC10 is a cell binding agent that is an antibody. Regarding claims 10-11 antibody cAC10 of Burke is capable of targeting tumor cells that are L540cy Hodgkin’s lymphoma cells. Regarding claim 12, Burke discloses pharmaceutically acceptable formulations comprising excipients (Burke, claims 93-94). Regarding claim 13, Burke discloses formulations comprising at least 0.01% of the conjugates of Burke by weight (Burke, ¶ 0480). Regarding claim 14, Burke discloses enclosing the pharmaceutical compositions of Burke in syringes (Burke, ¶ 0478). Regarding claim 15, the ADC of Burke exhibits in vitro cell killing activity vs L540cy Hodgkin’s lymphoma cells (Burke, ¶ 1441). Regarding claim 16, Burke discloses simultaneous administration of a chemotherapeutic agent and the conjugate of Burke (Burke, ¶ 0469-0470).
Regarding instant claim 7, the antibody cAC10 taught by Burke fully satisfies structure b-29 of claim 7:
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… in the embodiment wherein n = 0 (claim 7 recites m and n are 0-20 independently) and there is no drug-linker moiety and just an antibody.
Response to Arguments
Applicant's arguments filed 6/15/2026 have been fully considered but they are not persuasive.
Applicant’s arguments are based on the presence of the quaternary amine present in the compound of Burke, which Applicant claims is not encompassed by the instant claim set. Applicant asserts that Y1 is permitted to be CH2 or N and this excludes a quaternary amine. This is not persuasive because even if, for the sake of argument, that it was assumed that Y1 is not permitted to be a quaternary amine, the language of claim 1 is so broad that it is still anticipated by the structure of Burke in the case where: 1) Y1 is CH2, 2) R1 is absent, 3) R4 is H and 4) R2 and R3 come together to form a heterocycloalkyl moiety that is the quaternary amine-comprising 6-membered heterocycle of Burke.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claim(s) 1, 4, 7-8, and 10-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Burke (Burke, et al., WO 2017/096311 A1; Published 06/08/2017; Priority to 12/4/2015 by way of US 62/263,578, of record) as applied to claims 1, 4, 7-8 and 10-16 above and in further view of Mattes (Mattes, et al., Swiss Med. Weekly 2017 147:w14487, of record).
The teachings of Burke are discussed above.
Burke does not teach the simultaneous administration of the conjugates of Burke and a chemotherapeutic that is cyclophosphamide.
Mattes teaches that cyclophosphamide is a commonly prescribed single agent for non-Hodgkin’s lymphoma (Mattes, p1, ¶ 5, p 2, ¶ 1).
It would be prima facie obvious to one of ordinary skill in the art to combine the ADC of Burke and the cyclophosphamide of Mattes with the net results being a pharmaceutical composition comprising the ADC of Burke and cyclophosphamide that is administered to treat non-Hodgkin’s lymphoma. One of ordinary skill in the art would be motivated to do this in order to better treat non-Hodgkin’s lymphoma. One of ordinary skill in the art would have a reasonable expectation of success formulating a pharmaceutical composition comprising the ADC of Burke and cyclophosphamide that is administered to treat non-Hodgkin’s lymphoma because Burke teaches simultaneous administration of a chemotherapeutic and the ADC of Burke and that the ADC of Burke was able to selectively kill non-Hodgkin’s lymphoma cells and cyclophosphamide is also an agent that can treat non-Hodgkin’s lymphoma.
Response to Arguments
Applicant's arguments filed 6/15/2026 have been fully considered but they are not persuasive. Applicant grouped the arguments for the 102 and 103 rejections together and, as such, have already been addressed.
Conclusion
Claims 1-18 are rejected.
No claims are allowed.
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/SYDNEY VAN DRUFF/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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