DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The claim listing filed May 8, 2023 is pending.
Claims 1-122 are canceled.
Claims 123-142 are pending.
Claim 123 is an independent claim.
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Applicant’s election without traverse of Group I (claims 123-141, drawn to an antibody-drug conjugate and a pharmaceutical composition); and the species of:
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in the reply filed on November 21, 2025 is acknowledged.
Claims 130, 131, and 142 have been withdrawn from further consideration pursuant to 37 CFR
1.142(b) as being drawn to nonelected inventions.
Claims 123-129 and 132-141 are currently under consideration.
Claim Rejections - 35 USC § 112
Indefinite Language
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 127, 129, and 132 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 127 and 129 recite the phrase "optionally" which renders the claims indefinite because it is unclear whether the limitation(s) following the phrase is part of the claimed invention. See MPEP § 2173.05(d).
Claim 127 recites “optionally containing 1 to 3 additional heteroatoms selected from the group consisting of N, O, and S; and m is 0-3, q is 0-12, and r is 1-3” in lines 12-14.
Claim 129 recites “optionally substituted with the linker attached to the anti-TM4SF 1 antibody or the antigen-binding fragment thereof” in lines 6-7 and 8-9.
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Claim 132 lists this compound:
However, the claim does not recite what group R3 is. Thus, it is unclear what this compound is and as such renders claim 132 indefinite.
Written Description
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 123-129, 132-141 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 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.
The instant claims are drawn to an antibody-drug conjugate comprising:(a) an anti-TM4SF 1 antibody or an antigen-binding fragment thereof,(b) an antimitotic tetrapeptide; and (b) a linker between the anti-TM4SF 1 antibody or antigen-binding fragment thereof and the antimitotic tetrapeptide; and a pharmaceutical composition.
The Applicant discloses 12 anti-TM4SF1 antibodies: AGX-A01, AGX-A03, AGX-A04, AGX-A05, AGX-A07, AGX-A08, AGX-A09, AGX-A11, AGX-A07 H2v1L5v2, AGX-A07 H2L5, AGX-A01 H1L10, and AGX-A01 H1v1L10 (e.g. see Table 5).
The Applicant also discloses that the antimitotic tetrapeptide can be Tubulysins A-I, U, V, Y, Z, and pretubulysin, and a derivative thereof. As used herein, the term "derivative of tubulin" generally refers to analogs of tubulysin, including but not limited to, oxazole analogs of tubulysin in which an oxazole ring replaces the thiazole ring (e.g. see [0258]).
The claims encompass many linker options (e.g. see claims 124, 125, and 127). However, the Applicant has only disclosed 14 anti-TM4SF1 antibody-linker-tubulysin conjugates which comprise one of only seven linkers: BA-PEG2, mc-Lys-MMETA, mc-ValCit-PAB, 1-mc-ValCit-PAB(CI), 2-mc-ValCit-PAB(CI), BA-PEG4Ahx, and mc-ValCit-PAB(CI) (e.g. see tables 2-4). Furthermore, in these same ADCs, the Applicant has limited the antimitotic tetrapeptides to tubulysin or a derivative thereof (e.g. see tables 2-4).
When given the broadest reasonable interpretation in light of specification, the ADCs of the instant invention are defined broadly to be any ADC molecule that comprises any anti-TM4SF 1 antibody or an antigen-binding fragment thereof, any antimitotic tetrapeptide, and any linker between the anti-TM4SF 1 antibody or antigen-binding fragment thereof and the antimitotic tetrapeptide.
It is noted that the broadest claim (claim 123) does not indicate any specific structure for the genus of ADCs as claimed.
Claims 124-128 limit the structure of the linker to comprise certain elements or have certain properties.
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Claims 129, 132, and 133 limit the structure of the antimitotic tetrapeptide to:
Claims 138-140 limit the structure of the anti-TM4SF 1 antibody or antigen binding fragment thereof to those that comprise HCDRs1-3 and LCDRs1-3 with amino acid sequences with at least 75% sequence identity to SEQ ID NOs: 94-96 and 107, 109, and 110, respectively.
It is noted that no claim recites the complete structure of the ADC with each of these elements described sufficiently.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, January 5, 2001, see especially page 1106 column 3). In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
Regarding the anti-TM4SF 1 antibody or antigen binding fragment, artisans are well aware that knowledge of a given antigen (for instance CEA) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al. (J. Mol. Biol., 2003, 334:103-118) teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences spanning almost the entire heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines, and with extensive diversity in the HCDR3 region sequences (that are generated by VDJ germline segment recombination) as well, see entire document).
As such, it does not seem possible to predict the sequence/structure of an antibody that binds a given antigen, as there does not appear to be any common or core structure present within all antibodies that gives rise to the function of antigen binding. Further, given data, such as that of Edwards et al., indicating the diversity of sequences in a population of antibodies that bind to a given antigen, no number of species appears to reasonably representative of the breadth of the genus of antibodies that bind the given antigen.
It should be pointed out that it is well established in the art that the formation of an intact antigen-binding site requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three different complementarity determining regions, CDR1, 2 and 3, which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (Janeway Jr et al., Immunology, 3rd Edition, 1997 Garland Publishing Inc., pages 3:1-3:11.see entire selection).
Thus, based upon the prior art, skilled artisans would reasonably understand that it is the structure of the CDRs within an antibody which gives rise to the functional property of antigen binding, the epitope to which said CDRs bind is an inherent property which appears to necessarily be present due to conservation of critical structural elements, namely the CDR sequences themselves.
This applies to the instant invention which is drawn to a genus of ADCs that comprises an anti-TM4SF 1 antibody or an antigen-binding fragment thereof.
Regarding the linker the antimitotic tetrapeptide (or cytotoxic agent), Zolot et al. 2013 (Nat. Rev. Drug Discovery, 12, 259–260) teach that the linker (1) must be stable enough to ensure the ADC remains intact until it reaches the target, (2) does not alter the antibody characteristics (pharmacokinetics), and (3) sures that the cytotoxic agent is functional once at the target site (e.g. see Figure 1). Zolot et al. also teach that the cytotoxic agent must be (1) non-immunogenic, (2) non-toxic (dormant or inactive) during circulation in the blood, and (3) highly potent in small quantities such that two to four molecules are sufficient (e.g. see Figure 1).
Hamilton et al. 2021 (Chem. Med. Chem. 16(7):1077–1081) teach that tubulysins, which are antimitotic tetrapeptides, have emerged in recent years as a compelling drug class for delivery to tumor cells via antibodies (e.g. see Abstract). Tubulysin M, a synthetic analogue, has proven to be active and well tolerated as an antibody‐drug conjugate (ADC) payload, but has the liability of being susceptible to acetate hydrolysis at the C11 position, leading to attenuated potency. Conversion of the C11 acetate to a stabilized functional group, such as an ether, carbamate, or hindered ester, is a common strategy to circumvent this (e.g. see page 1077, right column, second paragraph). However, these stabilized analogues often underperform as ADC payloads relative to the parent C11 acetate congeners (e.g. see page 1077, right column, second paragraph). Thus, it appears that the C11 acetate present on tubulysin M is an important structural feature for maintaining cytotoxic activity (e.g. see paragraph spanning pages 1077 and 1078).
Hamilton et al. teach that in contrast to a more conventional protease‐cleavable dipeptide linker, the β‐glucuronidase‐cleavable glucuronide linker protects against acetate hydrolysis and improves ADC activity in vivo (e.g. see Abstract). In addition, site‐specific conjugation can positively impact both acetate stability and in vivo activity. Together, these findings provide the basis for a highly optimized delivery strategy for tubulysin M (e.g. see Abstract). Hamilton et al. further teach that both the linker chemistry and conjugation site can lead to significant improvements in tubulysin ADC in vivo activity (e.g. see paragraph spanning pages 1079 and 1080).
Hamilton et al. ultimately teach how pairing innovations in antibody engineering and drug‐linker design can optimize the targeted delivery of a promising payload (e.g. see page 1081, left column, third paragraph).
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Cong et al. 2017 (WO2017196598) also teach that the acetate group in the Tuv subunit appears to be essential for biological activity (e.g. see [0009]). Its removal (deacetylation), resulting in compounds in which R" in formula (A) is hydroxyl, reportedly leads to loss of biological activity. In a study of tubulysins U and V, which differ in the former being acetylated and the latter being deacetylated, tubulysin V was reported to be less potent by about 200X to 600X, depending on the assay (e.g. see [0009]). See structure copied below which points out the Tuv subunit. The acetate would be attached to R’’ of the Tuv subunit.
Cong et al. further teach that resistance to hydrolysis of the Tuv acetate group in an ADC can be enhanced by appropriate linker design and that the moiety on the linker resulting in such enhancement is located distally from the acetate group (e.g. see [0012]). Cong et al. teach that modifying the linker by locating a methyleneamino (CH2NH2) group adjacent to the maleimide group has the unexpected effect of stabilizing the Tuv acetate group against hydrolysis (e.g. see [0016]).
Thus, the art teaches how unpredictable it is to select an efficacious linker and antimitotic tetrapeptide pair when designing an ADC. It is not always obvious which linkers and antimitotic tetrapeptides will meet the criteria outlined by Zolot et al. or how they will perform when used together in an ADC.
As noted above, the Applicant has disclosed 12 anti-TM4SF1 antibodies and many linkers and antimitotic tetrapeptides. However, while the Applicant discloses a laundry list of linkers, the Applicant has only disclosed 14 examples of anti-TM4SF1 antibody-linker-tubulysin conjugates which comprise one of only seven linkers. Furthermore, in these same ADCs, the Applicant has limited the antimitotic tetrapeptides to tubulysin or a derivative thereof. Such a disclosure does not serve to provide sufficient written description of the claimed genus of ADCs that comprises any anti-TM4SF 1 antibody or an antigen-binding fragment thereof, any antimitotic tetrapeptide, and any linker between the anti-TM4SF 1 antibody or antigen-binding fragment thereof and the antimitotic tetrapeptide. Further, the disclosure does not identify any specific structural features or combination of features which give rise to a functional ADC that comprises all of these elements. Additionally, there does not appear to be any reasonable shared structure present in the genus of recited ADCs which gives rise to their functional activity. Ultimately, identifying an ADC simply on the basis of what it binds rather than by identifying the sequence/structure, namely the CDRs, the linker, and the antimitotic tetrapeptide, of the ADC in question is generally insufficient to provide written description of the ADC in question.
This reasoning further applies to claim 138 which recites the limitation “comprising an amino acid sequence that has at least 75% identity to a sequence.” Claim 138 does not satisfy the written description requirement because the claim language allows for up to 25% variability in the amino acid sequence structure of the antigen-binding domain, including the CDRs, which would be expected to impact the functional binding activity of the antigen-binding domain based on the state of the prior art. Claim 138 is drawn to a broad subgenus of antigen-binding domain structures which are functionally defined by their ability to bind to TM4SF1 without reciting a corresponding structure expected to correlate with this ability as supported by Applicant’s disclosure.
Thus, there is insufficient written description for the breadth of ADCs comprising any anti-TM4SF 1 antibody or an antigen-binding fragment thereof, any antimitotic tetrapeptide, and any linker between the anti-TM4SF 1 antibody or antigen-binding fragment thereof and the antimitotic tetrapeptide.
Therefore, in view of the breadth of the claims and the limited disclosure, artisans would reasonably conclude that applicant was not in possession of the full breadth of ADCs encompassed by the claims at the time the instant application was filed.
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.
Claims 123-125, 128, 133, and 138-141 are rejected under 35 U.S.C. 103 as being unpatentable over Cong et al. 2017 (WO2017196598) in view of Jaminet et al. 2018 (WO2019046338).
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Cong et al. teach the following structure of an antibody-drug conjugate (formula (II)):
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wherein, n can be 0, R1 can be Me, R2 can be , R3 can be Me, and R4 and R5 can be (CH2)4NH2 (lysine) (e.g. see [0017] and [0018]). Cong et al. also teach a pharmaceutical composition comprising the ADC and a pharmaceutically acceptable excipient (e.g. see claim 15).
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Cong et al. also teach that the acetate group in the Tuv subunit appears to be essential for biological activity (e.g. see [0009]). Its removal (deacetylation), resulting in compounds in which R" in formula (A) is hydroxyl, reportedly leads to loss of biological activity. In a study of tubulysins U and V, which differ in the former being acetylated and the latter being deacetylated, tubulysin V was reported to be less potent by about 200X to 600X, depending on the assay (e.g. see [0009]). See structure copied below which points out the Tuv subunit. The acetate would be attached to R’’ of the Tuv subunit.
Cong et al. do not teach that the antibody or antigen binding fragment thereof binds TM4SF1 or that the anti-TM4SF1 antibody or antigen binding fragment thereof comprises the CDRs and heavy and light chain amino acid sequences set forth in claims 138-140.
Jaminet et al. teach that transmembrane-4 L six family member-1 (TM4SF1) is a is a small plasma membrane glycoprotein that is highly expressed on tumor vasculature endothelial cells (ECs), tumor cells (TCs), ECs of developing retinal vasculature, and angiogenic blood vessels (e.g. see [0100]). It forms TM4SF1-enriched domains (TMED) on plasma membranes, where, like genuine tetraspanins, it serves as a molecular facilitator that recruits functionally related membrane and cytosolic molecules and plays important roles in cancer cell growth, motility, and metastasis (e.g. see [0133]).
Jaminet et al. also teach an anti-TM4SFl antibody, or antigen-binding fragment thereof that comprises a VH and VL, wherein the VH comprises SEQ ID NO: 90 and the VL comprises SEQ ID NO: 97. It is noted that Jaminet et al.’s SEQ ID NOs: 90 and 97 are identical to instant SEQ ID NOs: 90 and 97 which comprise HCDRs1-3 as SEQ ID NOs: 94-96, respectively, and LCDRs1-3 as SEQ ID NOs: 107, 109, and 110. See sequence alignments below. Jaminet et al. that the antibody comprising SEQ ID NOs: 90 and 97 is named hAGX-A07-H2L5 which displayed the strongest target binding with an EC50 of 1.53 nM (e.g. see Figure 12).
Alignment of instant and Jaminet et al.’s SEQ ID NO: 90 (CDRs are bolded and underlined):
Query Match 100.0%; Score 2409; DB 1; Length 450;
Best Local Similarity 100.0%;
Matches 450; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGVKWVRQAPGQDLEWMGWINTYTGNPIY 60
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Db 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYGVKWVRQAPGQDLEWMGWINTYTGNPIY 60
Qy 61 AADFKGRVTMTTDTSTSTAFMELRSLRSDDTAVYYCVRFQYGDYRYFDVWGQGTLVTVSS 120
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Db 61 AADFKGRVTMTTDTSTSTAFMELRSLRSDDTAVYYCVRFQYGDYRYFDVWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
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Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGA 240
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Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGA 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
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Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
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Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
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Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
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Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
Alignment of instant and Jaminet et al.’s SEQ ID NO: 97 (CDRs are bolded and underlined):
Query Match 100.0%; Score 1107; DB 1; Length 213;
Best Local Similarity 100.0%;
Matches 213; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIILTQSPATLSLSPGERATLSCRANSGISFINWYQQKPGQAPRLLIYGTANLASGIPAR 60
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Db 1 EIILTQSPATLSLSPGERATLSCRANSGISFINWYQQKPGQAPRLLIYGTANLASGIPAR 60
Qy 61 FGGSGSGRDFTLTISSLEPEDFAVYYCQQWSSNPLTFGGGTKVEIKRTVAAPSVFIFPPS 120
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Db 61 FGGSGSGRDFTLTISSLEPEDFAVYYCQQWSSNPLTFGGGTKVEIKRTVAAPSVFIFPPS 120
Qy 121 DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL 180
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Db 121 DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL 180
Qy 181 SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 213
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Db 181 SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 213
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Cong et al. to incorporate the teachings of Jaminet et al. to include that the antibody or antigen binding fragment thereof binds TM4SF1 or that the anti-TM4SF1 antibody or antigen binding fragment thereof comprises the CDRs and heavy and light chain amino acid sequences set forth in claims 138-140.
Given that TM4SF1 is highly expressed on tumor vasculature endothelial cells and plays important roles in cancer cell growth, motility, and metastasis; it would have been obvious to a skilled artisan to select TM4SF1 as the target for Cong et al.’s ADC with a reasonable expectation of success. Furthermore, given that hAGX-A07-H2L5 displayed the strongest target binding when compared to the other anti-TM4SF1 prepared by Jaminet et al.; it would have been obvious to a skilled artisan, with the goal of selecting the strongest target binder for Cong et al.’s ADC, to select Jaminet et al.’s hAGX-A07-H2L5 with a reasonable expectation of success.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 123, 126, and 127 are rejected under 35 U.S.C. 103 as being unpatentable over Cong et al. 2017 (WO2017196598) in view of Jaminet et al. 2018 (WO2019046338), as applied to claim 123, and further in view of Cheng et al. 2018 (Mol Cancer Ther; 17(12), 2665-2675).
The combined teachings of Cong et al. in view of Jaminet et al. pertaining to claim 123 and the rationale for combining them are outlined in the 103 rejection above.
The combined reference teachings differ from the instant invention by not teaching that the linker comprises PEG2, a non-cleavable linker.
Cheng et al. teach the design of microtubule-targeting ADCs (e.g. see Abstract). Cheng et al. also teach that when short (PEG2) spacers were used, conjugation was efficient (e.g. see paragraph spanning pages 2669 and 2670).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined teachings of Cong et al. in view of Jaminet et al. as applied to claim 123 and to incorporate the teachings of Cheng et al. to include that the linker comprises PEG2, a non-cleavable linker.
Given that short spacers, such as PEG2, which make up the linker, can be used to efficiently conjugate a cytotoxic drug to an antibody; it would have been obvious to a skilled artisan to introduce PEG2 to the anti-TM4SF1 ADC taught by Cong et al. in view of Jaminet et al. with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 123 and 129 are rejected under 35 U.S.C. 103 as being unpatentable over Cong et al. 2017 (WO2017196598) in view of Jaminet et al. 2018 (WO2019046338), as applied to claim 123, and further in view of Braig et al. 2017 (Cell Death Dis. 5, e1001, 1-11).
The combined teachings of Cong et al. in view of Jaminet et al. pertaining to claim 123 and the rationale for combining them are outlined in the 103 rejection above.
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The combined reference teachings differ from the instant invention by not teaching that antimitotic tetrapeptide has the following structure:
Braig et al. teach that pretubulysin is chemically accessible precursor of tubulysin that is a potent microtubule-binding agent produced by myxobacteria (e.g. see Abstract). Although much simpler in chemical structure, pretubulysin abrogates proliferation and long-term survival as well as anchorage-independent growth, and also induces anoikis and apoptosis in invasive tumor cells as well as tubulysin. Thus, Braig et al. teach that the microtubule-destabilizing compound pretubulysin as a highly promising novel agent for mono treatment and combinatory treatment of invasive cancer (e.g. see Abstract). The chemical structure of pretubulysin can be found in Braig et al.’s figure S1 (copied below).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined teachings of Cong et al. in view of Jaminet et al. as applied to claim 123 and to incorporate the teachings of Braig et al. to include that the antimitotic tetrapeptide is the elected species above.
Given that pretubulysin is chemically accessible, is an equally potent microtubule-binding agent to tubulysin, and ultimately its promise as an anti-cancer drug; it would have been obvious to a skilled artisan to specifically select pretubulysin as the antimitotic tetrapeptide for the anti-TM4SF1 ADC taught by Cong et al. in view of Jaminet et al. with a reasonable expectation of success.
Furthermore, given that the acetate group in the Tuv subunit appears to be essential for biological activity; it would have been obvious to a skilled artisan, with the goal of improving the biological activity of the anti-TM4SF1 ADC-pretubulysin, to experiment with putting an acetate group in the Tuv subunit of pretubulysin reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 123 and 134-137 are rejected under 35 U.S.C. 103 as being unpatentable over Cong et al. 2017 (WO2017196598) in view of Jaminet et al. 2018 (WO2019046338), as applied to claim 123, and further in view of Borrok et al. 2017 (J. Pharm. Sci. 106(4), 1008-1017).
The combined teachings of Cong et al. in view of Jaminet et al. pertaining to claim 123 and the rationale for combining them are outlined in the 103 rejection above.
The combined reference teachings differ from the instant invention by not teaching that the Fc region of the ADC comprises the point mutation M252Y, S254T, and T256E.
Borrok et al. teach that one set of mutations in the IgG1 CH2 domain, M252Y/S254T/T256E (also known as the YTE mutation), has been shown to increase the half-life of a monoclonal antibody to greater than 90 days in humans (e.g. see paragraph spanning pages 1008 and 1009). It is noted that instant SEQ ID NO: 151 in the natural IgG1 Fc region comprising the M252Y/S254T/T256E point mutations. Therefore, the Fc described by Borrok et al. would inherently have the same amino acid sequence as instant SEQ ID NO: 151, especially in the absence of evidence to the contrary.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined teachings of Cong et al. in view of Jaminet et al. as applied to claim 123 and to incorporate the teachings of Borrok to include that the Fc region of the ADC comprises the point mutation M252Y, S254T, and T256E.
Given that the YTE mutation is known to increase the half-life of a monoclonal antibody to greater than 90 days in humans; it would have been obvious to a skilled artisan to introduce the YTE mutation to the anti-TM4SF1 ADC taught by Cong et al. in view of Jaminet et al. in order to improve the half-life of the ADC with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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 123-128, 133, and 141 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 140-155 and 158 of Co-pending U.S. Application No. 18/161,405 (the ‘405 Application) in view of Cong et al. 2017 (WO2017196598).
The instant claims are drawn to an antibody-drug conjugate comprising:(a) an anti-TM4SF 1 antibody or an antigen-binding fragment thereof,(b) an antimitotic tetrapeptide; and (b) a linker between the anti-TM4SF 1 antibody or antigen-binding fragment thereof and the antimitotic tetrapeptide; and a pharmaceutical composition.
The claims in the ‘405 Application are drawn to an antibody drug conjugate comprising:(i) an anti-TM4SF1 antibody or an antigen binding fragment thereof; (ii) a therapeutic molecule; and (iii) a linker conjugated with the ani-TM4SF1 antibody and the therapeutic molecule; and a pharmaceutical composition.
The claims in the ‘405 Application differ from the instant invention by not teaching that the therapeutic molecule is an antimitotic tetrapeptide or a tubulysin recited in claim 133.
The teachings of Cong et al. are outlined in the 103 rejection above. Cong et al. also teach that tubulysins are anti-mitotic naturally occurring cytotoxins, first isolated from mycobacteria cultures (e.g. see [0006]). During mitosis, a cell's microtubules reorganize to form the mitotic spindle, a process requiring the rapid assembly and disassembly of microtubules from their constituent proteins a- and β-tubulin. The cytotoxicity of the tubulysins derives from their ability to prevent the assembly of the tubulins into microtubules, causing the affected cells to accumulate in the G2/M phase and undergo apoptosis. Tubulysins have long been proposed as suitable drug candidates for ADC (e.g. see [0006]).
It would be obvious to one of ordinary skill in the art to have modify the claims in the ‘405 Application to incorporate the teachings of Cong et al. to include that the therapeutic molecule is an antimitotic tetrapeptide or a tubulysin recited in claim 133.
Given the cytotoxicity of tubulysins and their success in being incorporated into ADCs as demonstrated by Cong et al.; it would be obvious to a skilled artisan to specifically select a tubulysin or a derivative thereof as the therapeutic agent in the ‘405 Patent’s ADC with a reasonable expectation of success.
Therefore, the claims in the ‘405 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 123 and 129 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 140-155 and 158 of Co-pending U.S. Application No. 18/161,405 (the ‘405 Application) in view of Cong et al. 2017 (WO2017196598), as applied to claim 123, and further in view of Braig et al. 2017 (Cell Death Dis. 5, e1001, 1-11).
The combined teachings of the claims of the ‘405 Application. in view of Cong et al. pertaining to claim 123 and the rationale for combining them are outlined in the NSDP rejection above.
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The combined reference teachings differ from the instant invention by not teaching that antimitotic tetrapeptide has the following structure:
The teachings of Braig et al. are outlined in the 103 rejection of claims 123 and 129 above.
It would be obvious to one of ordinary skill in the art to modify the combined teachings of the claims of the ‘405 Application. in view of Cong et al. as applied to claim 123 and to incorporate the teachings of Braig et al. to include that the antimitotic tetrapeptide is the elected species above.
Given that pretubulysin is chemically accessible, is an equally potent microtubule-binding agent to tubulysin, and ultimately its promise as an anti-cancer drug; it would be obvious to a skilled artisan to specifically select pretubulysin as the antimitotic tetrapeptide for the anti-TM4SF1 ADC taught by ‘405 Application in view of Cong et al. with a reasonable expectation of success.
Furthermore, given that the acetate group in the Tuv subunit appears to be essential for biological activity; it would be obvious to a skilled artisan, with the goal of improving the biological activity of the anti-TM4SF1 ADC-pretubulysin, to experiment with putting an acetate group in the Tuv subunit of pretubulysin reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the ‘405 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 123 and 134-137 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 140-155 and 158 of Co-pending U.S. Application No. 18/161,405 (the ‘405 Application) in view of Cong et al. 2017 (WO2017196598), as applied to claim 123, and further in view of Borrok et al. 2017 (J. Pharm. Sci. 106(4), 1008-1017).
The combined teachings of the claims of the ‘405 Application. in view of Cong et al. pertaining to claim 123 and the rationale for combining them are outlined in the NSDP rejection above.
The combined reference teachings differ from the instant invention by not teaching that the Fc region of the ADC may only comprise the point mutation M252Y, S254T, and T256E. It is noted that the ‘405 Application recites a large list of anti-TM4SF1 antibody species in claims 148-151 which includes the instantly elected species.
The teachings of Borrok et al. are outlined in the 103 rejection of claims 123 and 134-137 above.
It would be obvious to one of ordinary skill in the art to modify the combined teachings of the claims of the ‘405 Application. in view of Cong et al. as applied to claim 123 and to incorporate the teachings of Borrok to include that the Fc region of the ADC comprises the point mutation M252Y, S254T, and T256E.
Given that the YTE mutation is known to increase the half-life of a monoclonal antibody to greater than 90 days in humans; it would be obvious to a skilled artisan to introduce the YTE mutation to the anti-TM4SF1 ADC taught by the ‘405 Application in view of Cong et al. in order to improve the half-life of the ADC with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the ‘405 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 123 and 138-140 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 140-155 and 158 of Co-pending U.S. Application No. 18/161,405 (the ‘405 Application) in view of Cong et al. 2017 (WO2017196598), as applied to claim 123, and further in view of Jaminet et al. 2018 (WO2019046338).
The combined teachings of the claims of the ‘405 Application. in view of Cong et al. pertaining to claim 123 and the rationale for combining them are outlined in the NSDP rejection above.
The combined reference teachings differ from the instant invention by not teaching that the anti-TM4SF1 antibody or antigen binding fragment thereof may only comprise the elected CDRs and heavy and light chain amino acid sequences set forth in claims 138-140. It is noted that the ‘405 Application recites a large list of anti-TM4SF1 antibody species in claims 152-154 which includes the instantly elected species.
The teachings of Jaminet et al. are outlined in the 103 rejection of claims 123-125, 128, 133, and 138-141 above.
It would be obvious to one of ordinary skill in the art to modify the combined teachings of the claims of the ‘405 Application. in view of Cong et al. as applied to claim 123 and to incorporate the teachings of Jaminet et al. to include that the anti-TM4SF1 antibody or antigen binding fragment thereof may only comprise the elected CDRs and heavy and light chain amino acid sequences set forth in claims 138-140
Given that hAGX-A07-H2L5, which comprises the instantly elected antibody amino acid sequences, displayed the strongest target binding when compared to the other anti-TM4SF1 prepared by Jaminet et al.; it would have been obvious to a skilled artisan, with the goal of selecting the strongest target binder for the anti-TM4SF1 ADC taught by the ‘405 Application in view of Cong et al., to select Jaminet et al.’s hAGX-A07-H2L5 with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the ‘405 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 123-128, 133, and 141 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 139-155 of Co-pending U.S. Application No. 18/971,926 (the ‘926 Application) in view of Cong et al. 2017 (WO2017196598).
The instant claims are drawn to an antibody-drug conjugate comprising:(a) an anti-TM4SF 1 antibody or an antigen-binding fragment thereof,(b) an antimitotic tetrapeptide; and (b) a linker between the anti-TM4SF 1 antibody or antigen-binding fragment thereof and the antimitotic tetrapeptide; and a pharmaceutical composition.
The claims in the ‘926 Application are drawn to an antibody drug conjugate comprising:(i) an anti-TM4SF1 antibody or an antigen binding fragment thereof; (ii) a therapeutic molecule; and (iii) a linker conjugated with the ani-TM4SF1 antibody and the therapeutic molecule; and a pharmaceutical composition.
The claims in the ‘926 Application differ from the instant invention by not teaching that the therapeutic molecule is an antimitotic tetrapeptide or a tubulysin recited in claim 133.
The teachings of Cong et al. are outlined in the 103 rejection above. Cong et al. also teach that tubulysins are anti-mitotic naturally occurring cytotoxins, first isolated from mycobacteria cultures (e.g. see [0006]). During mitosis, a cell's microtubules reorganize to form the mitotic spindle, a process requiring the rapid assembly and disassembly of microtubules from their constituent proteins a- and β-tubulin. The cytotoxicity of the tubulysins derives from their ability to prevent the assembly of the tubulins into microtubules, causing the affected cells to accumulate in the G2/M phase and undergo apoptosis. Tubulysins have long been proposed as suitable drug candidates for ADC (e.g. see [0006]).
It would be obvious to one of ordinary skill in the art to have modify the claims in the ‘926 Application to incorporate the teachings of Cong et al. to include that the therapeutic molecule is an antimitotic tetrapeptide or a tubulysin recited in claim 133.
Given the cytotoxicity of tubulysins and their success in being incorporated into ADCs as demonstrated by Cong et al.; it would be obvious to a skilled artisan to specifically select a tubulysin or a derivative thereof as the therapeutic agent in the ‘926 Patent’s ADC with a reasonable expectation of success.
Therefore, the claims in the ‘926 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 123 and 129 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 139-155 of Co-pending U.S. Application No. 18/971,926 (the ‘926 Application) in view of Cong et al. 2017 (WO2017196598), as applied to claim 123, and further in view of Braig et al. 2017 (Cell Death Dis. 5, e1001, 1-11).
The combined teachings of the claims of the ‘926 Application. in view of Cong et al. pertaining to claim 123 and the rationale for combining them are outlined in the NSDP rejection above.
The combined reference teachings differ from the instant invention by not teaching that antimitotic tetrapeptide has the following structure:
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The teachings of Braig et al. are outlined in the 103 rejection of claims 123 and 129 above.
It would be obvious to one of ordinary skill in the art to modify the combined teachings of the claims of the ‘926 Application. in view of Cong et al. as applied to claim 123 and to incorporate the teachings of Braig et al. to include that the antimitotic tetrapeptide is the elected species above.
Given that pretubulysin is chemically accessible, is an equally potent microtubule-binding agent to tubulysin, and ultimately its promise as an anti-cancer drug; it would be obvious to a skilled artisan to specifically select pretubulysin as the antimitotic tetrapeptide for the anti-TM4SF1 ADC taught by ‘926 Application in view of Cong et al. with a reasonable expectation of success.
Furthermore, given that the acetate group in the Tuv subunit appears to be essential for biological activity; it would be obvious to a skilled artisan, with the goal of improving the biological activity of the anti-TM4SF1 ADC-pretubulysin, to experiment with putting an acetate group in the Tuv subunit of pretubulysin reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the ‘926 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 123 and 134-137 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 139-155 of Co-pending U.S. Application No. 18/971,926 (the ‘926 Application) in view of Cong et al. 2017 (WO2017196598), as applied to claim 123, and further in view of Borrok et al. 2017 (J. Pharm. Sci. 106(4), 1008-1017).
The combined teachings of the claims of the ‘926 Application. in view of Cong et al. pertaining to claim 123 and the rationale for combining them are outlined in the NSDP rejection above.
The combined reference teachings differ from the instant invention by not teaching that the Fc region of the ADC may only comprise the point mutation M252Y, S254T, and T256E. It is noted that the ‘926 Application recites a large list of anti-TM4SF1 antibody species in claim 152 which includes the instantly elected species.
The teachings of Borrok et al. are outlined in the 103 rejection of claims 123 and 134-137 above.
It would be obvious to one of ordinary skill in the art to modify the combined teachings of the claims of the ‘926 Application. in view of Cong et al. as applied to claim 123 and to incorporate the teachings of Borrok to include that the Fc region of the ADC comprises the point mutation M252Y, S254T, and T256E.
Given that the YTE mutation is known to increase the half-life of a monoclonal antibody to greater than 90 days in humans; it would be obvious to a skilled artisan to introduce the YTE mutation to the anti-TM4SF1 ADC taught by the ‘926 Application in view of Cong et al. in order to improve the half-life of the ADC with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the ‘926 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 123 and 138-140 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 139-155 of Co-pending U.S. Application No. 18/971,926 (the ‘926 Application) in view of Cong et al. 2017 (WO2017196598), as applied to claim 123, and further in view of Borrok et al. 2017 (J. Pharm. Sci. 106(4), 1008-1017) and Jaminet et al. 2018 (WO2019046338).
The combined teachings of the claims of the ‘926 Application. in view of Cong et al. pertaining to claim 123 and the rationale for combining them are outlined in the NSDP rejection above.
The combined reference teachings differ from the instant invention by not teaching that the Fc region of the ADC may only comprise the point mutation M252Y, S254T, and T256E or the anti-TM4SF1 antibody or antigen binding fragment thereof may only comprise the elected CDRs and heavy and light chain amino acid sequences set forth in claims 138-140. It is noted that the ‘926 Application recites a large list of anti-TM4SF1 antibody species in claims 152-154 which includes the instantly elected species.
The teachings of Borrok et al. are outlined in the 103 rejection of claims 123 and 134-137 above and the teachings of Jaminet et al. are outlined in the 103 rejection of claims 123-125, 128, 133, and 138-141 above.
It would be obvious to one of ordinary skill in the art to modify the combined teachings of the claims of the ‘926 Application. in view of Cong et al. as applied to claim 123 and to incorporate the teachings of Borrok et al. and Jaminet et al. to include that the Fc region of the ADC may only comprise the point mutation M252Y, S254T, and T256E and the anti-TM4SF1 antibody or antigen binding fragment thereof may only comprise the elected CDRs and heavy and light chain amino acid sequences set forth in claims 138-140.
Given that the YTE mutation is known to increase the half-life of a monoclonal antibody to greater than 90 days in humans; it would be obvious to a skilled artisan to introduce the YTE mutation to the anti-TM4SF1 ADC taught by the ‘926 Application in view of Cong et al. in order to improve the half-life of the ADC with a reasonable expectation of success.
Furthermore, given that hAGX-A07-H2L5, which comprises the instantly elected antibody amino acid sequences, displayed the strongest target binding when compared to the other anti-TM4SF1 prepared by Jaminet et al.; it would have been obvious to a skilled artisan, with the goal of selecting the strongest target binder for the anti-TM4SF1 ADC taught by the ‘926 Application in view of Cong et al., to select Jaminet et al.’s hAGX-A07-H2L5 with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the ‘926 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/GRACE H LUNDE/Examiner, Art Unit 1641
/CHUN W DAHLE/Primary Examiner, Art Unit 1641