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 . 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.
Election/Restrictions
Applicants elected compound 2 of example 2 to treat diffuse large B cell lymphoma without traverse in the reply filed on 7 Nov, 2023.
Claims Status
Claims 80-83 are pending.
Withdrawn Rejections
The provisional rejection of claims 80-83 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 27, and 30 Application No. 19/030,299 in view of Sehn et al (J. Clin. Oncol. (2019) 38(2) p155-176) is hereby withdrawn due to the abandonment of the competing application.
Maintained/Modified Rejections
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.
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.
first rejection
Claim(s) 80-83 are rejected under 35 U.S.C. 103 as being unpatentable over Marshall et al (US 20210009719, cited by applicants) in view of Sehn et al (J. Clin. Oncol. (2019) 38(2) p155-176), with evidentiary support from Akaiwa et al (Chem. Pharm. Bull. (March 2020) 68(3) 201-211).
Marshall et al discuss peptide conjugates of cytotoxins for treating cancer (title and abstract). The structure of the peptide conjugates are simple; fitting the structure R8-Q-R7 (paragraph 28), where R7 is a peptide (paragraph 29), Q is a linker (paragraph 31), and R8 is a class of small molecule anticancer agents (paragraph 30). The peptide can be one that selectively delivers a payload to hypoxic cells or those in an acidic environment, with a pH less than 6 (paragraph 80). Among the peptides described as having these capabilities is SEQ ID 1, identical to SEQ ID 1 of the instant claims (paragraph 84). An example is given of a compound:
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(paragraph 175). Note that this is identical to applicant’s elected species
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save that the therapeutic is a camptothecin analog rather than MMAE. This compound is claimed (claim 49), and was synthesized by the authors of the paper (example 15, starts at paragraph 523), showing that the authors are clearly interested in this compound, that it appropriate as a lead compound. Among the cancers that can be treated by the invention are various lymphomas, including DLBCL, applicant’s elected disorder to be treated (paragraph 248). Pharmaceutically acceptable compositions are discussed, including pharmaceutically acceptable carriers (paragraph 275).
The difference between this reference and the instant claims is that this reference uses a different drug moiety in their construct.
Sehn et al discuss a clinical trial of polatuzumab vedotin for DLBCL (title). This is an antibody drug conjugate, with the drug being monomethyl auristatin E (p155, 2nd column, 2nd paragraph), which, as evidenced by Akaiwa et al, is the drug used in applicant’s elected species (fig 1, p202, top of page). Significantly more patients went into remission with this therapy combined with standard of care vs. standard of care alone (p163, 2nd column, 3d paragraph). This reference shows that constructs similar to that claimed by applicant, MMAE combined with a polypeptide binding agent, is effective in treating applicant’s elected disorder.
Therefore, it would be obvious to substitute the MMAE of Sehn et al for the camptothecin analogs of Marshall et al as a simple substitution of one known element (the camptothecin analogs of Marshal et al) for another (the auristatin analogs of Sehn et al) yielding expected results (tumor therapy). As Sehn et al shows a similar construct is effective in that disorder, an artisan in this field would attempt this modification with a reasonable expectation of success.
The combination of references generates a peptide of SEQ ID 1 attached to MMAE via a 1 thio 2 hydroxy cyclopentane ring, attached to the drug via a urethane bond with a nitrogen in the drug. Thus, the combination of references renders obvious claims 80 and 81.
Marshall et al discuss pharmaceutically acceptable formulations with carriers, rendering obvious claims 82 and 83.
response to applicant’s arguments
Applicants have attempted to disqualify Marshall et al as prior art with a declaration by Prof. Robert Maguire, inventor.
Applicant's arguments filed 15 May, 2026 have been fully considered but they are not persuasive.
Prof. Maguire states that the two inventors of Marshall et al that are not inventors for the examined claims worked on peptide conjugates of topoisomerase I inhibitors, rather than MMAE conjugates. As evidenced by the Boc sciences web page on exatecan (April, 2021), this is the structure of the drug used in Marshall et al relied upon in the rejection (3d page, top of page), which is a topoisomerase I inhibitor (2nd page, 1st paragraph). Mr. Maguire’s declaration does not show that the two inventors of Marshall et al who are not inventors of the examined claims did not work on the compound relied upon in the rejection, but rather state that they did not work on MMAE conjugates. Note that Marshall et al does not discuss MMAE conjugates; otherwise, the reference would have anticipated.
second rejection
Claim(s) 80-83 are rejected under 35 U.S.C. 103 as being unpatentable over Marshall et al (US 20190209580, cited by applicants) in view of Sehn et al (J. Clin. Oncol. (2019) 38(2) p155-176), with evidentiary support from Akaiwa et al (Chem. Pharm. Bull. (March 2020) 68(3) 201-211).
Marshall et al discuss compounds for treating diseases with acidic or hypoxic tissues (title and abstract). The structure of the peptide conjugates is simple; fitting the structure R8-Q-R7 (paragraph 11), where R8 is a pH sensitive peptide, Q is a linker, and R7 is a therapeutic molecule (paragraph 12). The peptide can be one that selectively delivers a payload to hypoxic cells or those in an acidic environment, with a pH less than 6 (paragraph 46). Among the peptides described as having these capabilities is SEQ ID 1, identical to SEQ ID 1 of the instant claims (paragraph 48). Among the linkers used in the examples is compound 1.6, with the structure:
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. This linker reads on applicant’s claims (G1 is a bond, m=2, n=0, Rs and Rt = a spiro compound or H, G2=O, OC(O)NRG or OC(O), depending on how it is linked to the therapeutic). Note that this is identical to applicant’s elected linker species if one side of the ring is moved to the methylene carbon, which is merely a shift of substituents on a core structure and not considered a patentable distinction (MPEP 2144.09 (II)). This modification is also suggested by Marshall et al, as it is allowed by the description of the linker (paragraph 29). Note that there are three examples (compounds 24, 39, and 44, out of 61 total compounds) using this linker. Given the large number of possible linkers that meet the description given by the authors, this indicates that they were very interested in this linker, making it a reasonable structure to start modifying. Among the cancers that can be treated by the invention are various lymphomas, including DLBCL, applicant’s elected disorder to be treated (paragraph 184). Pharmaceutically acceptable compositions, with appropriate carriers, are discussed (paragraph 211).
The difference between this reference and the instant claims is that this reference uses a different drug moiety in their construct and a slightly different linker than the elected species.
Sehn et al discuss a clinical trial of polatuzumab vedotin for DLBCL (title). This is an antibody drug conjugate, with the drug being monomethyl auristatin E (p155, 2nd column, 2nd paragraph), which, as evidenced by Akaiwa et al, is the drug used in applicant’s elected species (fig 1, p202, top of page). Significantly more patients went into remission with this therapy combined with standard of care vs. standard of care alone (p163, 2nd column, 3d paragraph). This reference shows that constructs similar to that claimed by applicant, MMAE combined with a polypeptide binding agent, is effective in treating applicant’s elected disorder.
Therefore, it would be obvious to substitute the MMAE of Sehn et al for the camptothecin analogs of Marshall et al as a simple substitution of one known element for another yielding expected results. As Sehn et al shows a similar construct is effective in that disorder, an artisan in this field would attempt this modification with a reasonable expectation of success.
The combination of references generates a peptide of SEQ ID 1 attached toMMAE via a 1 thio 2 hydroxy cyclopropane ring, attached to the drug via a urethane bond with a nitrogen in the drug. Thus, the combination of references renders obvious claims 80 and 81.
Marshall et al discuss pharmaceutically acceptable formulations with a carrier, rendering obvious claim 82 and 83.
response to applicant’s arguments
Applicants argue that this is a different isomer than that the courts have approved of, that small differences in the linker can lead to large differences in properties, that a person of skill in the art would chose a different lead compound, that there is no reason to modify the compounds of Marshall et al, that the cyclobutene linker would be expected to have different properties (more rotational freedom), that a genus does not render a species obvious, that there is no reason to select the peptide of Marshall et al, and that there are a number of generic linkers to select from disclosed by the reference.
Applicant's arguments filed 15 May, 2026 have been fully considered but they are not persuasive.
Applicants argue that the courts have not stated that the modification to the linker is obvious; that it is a different type of isomer. Applicants have fixated on names; the issue is similarity – compounds of similar structure would be expected to behave similarly. The only difference between the linker of the prior art compound and the linker claimed by applicants is that one carbon has been shifted over – an analog which is specifically allowed by the reference. In other words, these have a very similar structure, and so would be expected to behave similarly.
Applicants argue that small differences in structure can lead to large differences in properties. While true, the assumption is that similar compounds have similar properties, unless proven differently. Applicants have not demonstrated that the linker of the prior art has significantly different properties than the linker they have claimed.
Applicants have spent several pages listing why they would not select the compound of Marshal et al used in the rejection as a lead compound. However, the fact that applicants can find reasons to select a different lead compound does not mean that the reason given in the rejection to select that lead compound is invalid.
Applicants argue that there is no reason to modify the compound of Marshal et al. While the rejection does not use a teaching, suggestion, motivation rationale to combine the reference, that is not the only rationale that can be used, and the use of a different rationale does not make the rejection invalid (MPEP 2145(X)(C)).
Applicants argue that the prior art linker will have more rotational freedom than the one they have claimed; an argument that the linkers have different properties. Applicants have not demonstrated that this makes a meaningful difference in the medicinal properties of the construct.
Applicants argue that a genus does not render a species obvious. Applicants have not shown how this applies to the rejection.
Applicants argue that Marshal et al discloses a number of peptides, with no reason given to use the same peptide as the examined claims. However, the species selected for amendment uses the same peptide. In addition, while a number of sequences are disclosed, only three appear to have been used (note table 24, starting on p66). That is a small enough genus to render any one of them obvious.
Applicants argue that there are a number of generic linkers disclosed by Marshall et al. However, as noted in the rejection, there is a reason to select the one in the rejection for further modification.
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.
first rejection
Claims 80-83 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 14 of U.S. Patent No. 12,234,212 view of Sehn et al (J. Clin. Oncol. (2019) 38(2) p155-176), with evidentiary support from Akaiwa et al (Chem. Pharm. Bull. (March 2020) 68(3) 201-211).
Competing claim 1 describes a drug-linker-peptide composition for treating cancer, while competing 5 specifies that the peptide identically as the examined claims. Competing claim 14 requires the linker to be
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, which differs from applicant’s elected linker by the number of methylene groups in the ring, which is not considered a patentable distinction absent secondary considerations (MPEP 2144.09(II)).
The difference between the competing claims and the examined claims is that the competing claims uses a different drug moiety in their construct and a slightly different linker than the elected species.
Sehn et al discuss a clinical trial of polatuzumab vedotin for DLBCL (title). This is an antibody drug conjugate, with the drug being monomethyl auristatin E (p155, 2nd column, 2nd paragraph), which, as evidenced by Akaiwa et al, is the drug used in applicant’s elected species (fig 1, p202, top of page). Significantly more patients went into remission with this therapy combined with standard of care vs. standard of care alone (p163, 2nd column, 3d paragraph). This reference shows that constructs similar to that claimed by applicant, MMAE combined with a polypeptide binding agent, is effective in treating applicant’s elected disorder.
Therefore, it would be obvious to substitute the MMAE of Sehn et al for the camptothecin analogs of the competing claims as a simple substitution of one known element for another yielding expected results. As Sehn et al shows a similar construct is effective in that disorder, an artisan in this field would attempt this modification with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants argue that there is no motivation to use the specific linker, and that a cyclopentane ring has superior therapeutic properties; an argument that the assumption of similar properties is invalid. This is supported by a pair of declarations, one by Prof Robert Maguire, inventor and one by Prof. Sophia Gayle, employee of applicant.
Applicant's arguments filed 19 May, 2026 have been fully considered but they are not persuasive.
Applicants argue that the claims allow for a large number of different linkers, so there is no reason to select the linker used in the rejection. However, applicants are ignoring that the specific linker used in the rejection was described in the claims.
Applicants further argue that the assumption used in the rejection, that a slightly smaller ring will have similar properties, is incorrect. This has not been proven. A cardinal rule of experimentation is to change only one variable at a time (Twist, sciencing.com (2022) Why Should You Only Test For One Variable At A Time In An Experiment?, entire document). The declaration of Prof. Maguire describes an experiment where different linkers using a Maytansinoid warhead gave different pharmacokinetics. However, not enough detail is given of the experiment to demonstrate that the only difference is the linker. The declaration of Prof. Gayle describes an efficacy experiment. However, there are numerous issues with the experiment. First, compound 2 uses an MMAE warhead, while compound E2 uses an exatecan warhead (compare paragraph 4 to paragraph 6). Second, a different dose schedule was used (paragraph 7). Third, the treatment was started at a different tumor size (paragraph 7). This makes it unclear if the differences are due to the linker.
This approach can be effective. For the experiments described by Prof. Gayle, applicants will have to persuasively demonstrate that the differences between the two groups would not affect the conclusions applicants are drawing. For the experiments described by Prof. Maguire, applicants will have to provide enough detail of the experiments to show that the size of the ring in the linker is the only variable, or enough detail to show all other differences between the experiments, along with persuasive evidence that these differences would not be expected to affect the conclusion.
second rejection
Claims 80-83 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 7, 14, of U.S. Patent No. 12,410,262 in view of Sehn et al (J. Clin. Oncol. (2019) 38(2) p155-176), with evidentiary support from Akaiwa et al (Chem. Pharm. Bull. (March 2020) 68(3) 201-211).
Competing claim 1 describes a drug-linker-peptide composition for treating cancer, while competing 6 specifies that the peptide selectively delivers the material across a cell membrane in an acidic (<pH 6) or hypoxic mantle. Competing claim 7 lists a small number of peptides, including Pv1, identical with Pv1 of the examined claims, for use in this invention. Competing claim 14 requires the linker to be
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, which differs from applicant’s elected linker by the number of methylene groups in the ring, which is not considered a patentable distinction (MPEP 2144.09(II)). Competing claim 16 describes a small number of compounds, including
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. Note that this differs from applicant’s elected species in the size of the ring of the linker (which, as noted above, is not a patentable distinction) and the therapeutic.
The difference between the competing claims and the examined claims is that the competing claims uses a different drug moiety in their construct and a slightly different linker than the elected species.
Sehn et al discuss a clinical trial of polatuzumab vedotin for DLBCL (title). This is an antibody drug conjugate, with the drug being monomethyl auristatin E (p155, 2nd column, 2nd paragraph), which, as evidenced by Akaiwa et al, is the drug used in applicant’s elected species (fig 1, p202, top of page). Significantly more patients went into remission with this therapy combined with standard of care vs. standard of care alone (p163, 2nd column, 3d paragraph). This reference shows that constructs similar to that claimed by applicant, MMAE combined with a polypeptide binding agent, is effective in treating applicant’s elected disorder.
Therefore, it would be obvious to substitute the MMAE of Sehn et al for the camptothecin analogs of the competing claims as a simple substitution of one known element for another yielding expected results. As Sehn et al shows a similar construct is effective in that disorder, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants argue that the differences in the structure of the linker lead to differences in efficacy (i.e. the assumption of similar properties is invalid), that the claimed material is unexpectedly more potent, that there is no motivation to combine, and that there is no reason to select the compound used in the rejection to modify. These are supported by declarations by by Prof Robert Maguire, inventor and Prof. Sophia Gayle, employee of applicant.
Applicant's arguments filed 19 May, 2026 have been fully considered but they are not persuasive.
Applicants argue that the assumption in the rejection of similar structure leads to similar properties is invalid. As noted in the response to arguments to the first double patenting rejection, this has not been demonstrated.
Applicants argue that the claimed material is unexpectedly more effective, based on a declaration by Prof. Gayle. There are two issues with this argument. First, as noted in the response to the first double patenting rejection, both the dosing schedule and the patient population has changed between the two experiments; it is not clear if this plays a role in the conclusions applicants have drawn. Second, it is not clear why this would be considered unexpected. MMAE is a microtubule targeting agent (Best et al, Toxicol. Appl. Pharmacol. (2021) 421 115534, abstract). According to the Boc sciences web page on exatecan (April, 2021), exatecan is typically 10-100 times less potent than microtubule inhibitors (3d page, 2nd paragraph).
Applicants argue that there is no motivation to combine. Teaching, suggestion, motivation rationales are not the only rationales that can be used in a rejection (MPEP 2145(X)(C)).
Applicants state that there is no motivation to select the compound used in the rejection for modification. The compound was explicitly claimed in the competing claims; that gives ample reason to believe the authors believed it was important, and, hence, a reasonable starting point for modification.
third rejection
Claims 80-83 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 12 of US Patent No. 11,555,019 (reference application) in view of Sehn et al (J. Clin. Oncol. (2019) 38(2) p155-176), with evidentiary support from Akaiwa et al (Chem. Pharm. Bull. (March 2020) 68(3) 201-211).
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Competing claim 1 describes a drug-linker-peptide composition, while competing 2 specifies that the peptide selectively delivers the material across a cell membrane in an acidic (<pH 6) or hypoxic mantle. Comepting claim 3 lists a small number of peptides, including Pv1, identical with Pv1 of the examined claims, for use in this invention. Competing claim 12 requires the linker to be
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, which differs from applicant’s elected linker by the number of methylene groups in the ring, which is not considered a patentable distinction (MPEP 2144.09(II)).
The difference between the competing claims and the examined claims is that the competing claims uses a different drug moiety in their construct and a slightly different linker than the elected species.
Sehn et al discuss a clinical trial of polatuzumab vedotin for DLBCL (title). This is an antibody drug conjugate, with the drug being monomethyl auristatin E (p155, 2nd column, 2nd paragraph), which, as evidenced by Akaiwa et al, is the drug used in applicant’s elected species (fig 1, p202, top of page). Significantly more patients went into remission with this therapy combined with standard of care vs. standard of care alone (p163, 2nd column, 3d paragraph). This reference shows that constructs similar to that claimed by applicant, MMAE combined with a polypeptide binding agent, is effective in treating applicant’s elected disorder.
Therefore, it would be obvious to substitute the MMAE of Sehn et al for the camptothecin analogs of the competing claims as a simple substitution of one known element for another yielding expected results. As Sehn et al shows a similar construct is effective in that disorder, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants have repeated the same arguments used with respect to the first double patenting rejection. Those arguments were answered there.
fourth rejection
Claims 80-83 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 10 of US Patent No. 11,634,508 (reference application) in view of Sehn et al (J. Clin. Oncol. (2019) 38(2) p155-176), with evidentiary support from Akaiwa et al (Chem. Pharm. Bull. (March 2020) 68(3) 201-211).
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Competing claim 1 describes a drug-linker-peptide composition, while competing 2 specifies that the peptide selectively delivers the material across a cell membrane in an acidic (<pH 6) or hypoxic mantle. Comepting claim 3 lists a small number of peptides, including Pv1, identical with Pv1 of the examined claims, for use in this invention. Competing claim 10 requires the linker to be
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, which differs from applicant’s elected linker by the number of methylene groups in the ring, which is not considered a patentable distinction (MPEP 2144.09(II)). While the competing claims do not specify the utility of the invention, the disclosure states its for treatment of cancer (column 66, line 63). Note that the utility of the competing claims is one of the few areas that a competing disclosure can be used in a double patenting rejection (MPEP 804 (II)(B)(1)).
The difference between the competing claims and the examined claims is that the competing claims uses a different drug moiety in their construct and a slightly different linker than the elected species.
Sehn et al discuss a clinical trial of polatuzumab vedotin for DLBCL (title). This is an antibody drug conjugate, with the drug being monomethyl auristatin E (p155, 2nd column, 2nd paragraph), which, as evidenced by Akaiwa et al, is the drug used in applicant’s elected species (fig 1, p202, top of page). Significantly more patients went into remission with this therapy combined with standard of care vs. standard of care alone (p163, 2nd column, 3d paragraph). This reference shows that constructs similar to that claimed by applicant, MMAE combined with a polypeptide binding agent, is effective in treating applicant’s elected disorder.
Therefore, it would be obvious to substitute the MMAE of Sehn et al for the camptothecin analogs of the competing claims as a simple substitution of one known element for another yielding expected results. As Sehn et al shows a similar construct is effective in that disorder, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants repeat the arguments used with respect to the second double patenting rejection, which were answered there.
fifth rejection
Claims 80-83 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 51 of copending Application No. 19/281,226 in view of Sehn et al (J. Clin. Oncol. (2019) 38(2) p155-176), with evidentiary support from Akaiwa et al (Chem. Pharm. Bull. (March 2020) 68(3) 201-211).
Competing claim 51 describes a method using the compound
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. Note that this is identical with applicant’s elected species save for a slightly larger ring, which is not a patentable distinction (MPEP 2144.09) and different therapeutic moiety.
The difference between the competing claims and the examined claims is that the competing claims uses a different drug moiety in their construct, in addition to a non-patentable difference in the linker.
Sehn et al discuss a clinical trial of polatuzumab vedotin for DLBCL (title). This is an antibody drug conjugate, with the drug being monomethyl auristatin E (p155, 2nd column, 2nd paragraph), which, as evidenced by Akaiwa et al, is the drug used in applicant’s elected species (fig 1, p202, top of page). Significantly more patients went into remission with this therapy combined with standard of care vs. standard of care alone (p163, 2nd column, 3d paragraph). This reference shows that constructs similar to that claimed by applicant, MMAE combined with a polypeptide binding agent, is effective in treating applicant’s elected disorder.
Therefore, it would be obvious to substitute the MMAE of Sehn et al for the camptothecin analogs of the competing claims as a simple substitution of one known element for another yielding expected results. As Sehn et al shows a similar construct is effective in that disorder, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants argue that the competing claims have been amended so the species used in the rejection is no longer claimed.
Applicant's arguments filed 19 May, 2026 have been fully considered but they are not persuasive.
The rejection has been modified to account for the changes in the competing claims.
Examiner’s Note
The application list Cybrexa 4 as the applicant and assignee. However, the various declarations filed with the last response refer to the company this application is assigned to as Cybrexa. It is noted that there is a Cybrexa, Cybrexa 1, Cybrexa 2, Cybrexa 3, and Cybrexa 4 as applicants describing similar inventions having overlapping inventors. It is assumed that these are all the same company.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
Examiner interviews are available via telephone and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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