DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I and species of 177Lu-HTKO1169 in the reply filed on March 26, 2026 is acknowledged.
Drawings
The drawings are objected to because object because the individual curves and data points representing different experimental groups in Figure 6 are not clearly distinguishable. Specifically, the legend lists six experimental groups but the graph displays only five distinct curves. It is unclear whether the horizontal line at the 1.0 survival level represents actual data for one of the treatment groups as there are no distinct data points or symbols visible on that line. It is unclear whether two data series may be perfectly overlapping or one series has been omitted form the plot entirely. This discrepancy creates ambiguity as to which curve corresponds to which group. To overcome this objection, the applicant is required to provide a substitute sheet for Figure 6 that ensures all six data series are clearly identifiable. The applicant may utilize distinct line patterns, varied symbol types, and/or lead lines with reference numerals/labels.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Appropriate correction is required.
Specification
The disclosure is objected to because of the following informalities:
The use of the terms Endeavor 90®, 4000 QTRAP®, Luna®, Wizard2®, GraphPad Prism®, Inveon Research Workplace®, FreeZone Plus™, and Sep-Pak® which are a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
Claims 1, 30, and 46 are objected to because of the following informalities:
In claim 1, “R2 is … NO2 or CH3;” should read “R2 is … NO2, or CH3;” (add “,” in front of “or”).
In claim 1, “R3 is … or …” should read “R3 is … , or …” (add “,” in front of “or”).
In claim 30, “SarAr … or a derivative thereof;” should read “SarAr …) or a derivative thereof;” (add “)” in front of “or”).
In claim 30, “TRAP … acid) or a derivative thereof;” should read “TRAP … acid]) or a derivative thereof;” (add “ ]” in front of “)”).
In claim 46, “R2 is I, Br or …” should read “R2 is I, Br, or …” (add “,” in front of “or”).
In claim 46, “X is absent, 225Ac or 177Lu.” should read “X is absent, 225Ac, or 177Lu.” (add “,” in front of “or”).
Appropriate correction is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-3, 12, 15, 25, 30, 31, 35, 40, 42, and 43 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Benesova et al. (WO 2018 215627; cited on IDS filed November 21, 2023).
Regarding claims 1, 2, 12, 15, 25, 30, 31, 35, and 40, Benesova discloses a compound comprising a chelating agent, a prostate specific membrane antigen (PSMA)-binding entity, and an albumin-binding entity connected via suitable linkers and spacers for use as diagnostic and/or therapeutic radiopharmaceuticals (page 1, ¶ 1). Benesova discloses a compound of General Formula (7b) shown in claim 25, which reads on the Formula I-a of instant claim 1 when R1 is I in para position; R2 is H; n is 1; V is N; D is 1,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid (DOTA); and a is 4. Benesova discloses that the amino acid residue (A) can be glutamate (claim 26). Benesova discloses that the glutamate can be bonded through Cdelta (γ -linkage) as shown in Formula (3b) when m is 2 and n is 1 (claim 27), which reads on
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(R3) of instant claims 1 and 25.
Regarding claim 3, Benesova discloses a compound of General Formula (7b) shown in claim 25, which reads on the Formula I-b of instant claims 1 and 3 when R1 is I in para position; R2 is H; n is 1; V is -CH2NH-; D is DOTA; and a is 0. Benesova discloses that the A can be glutamate (claim 26) and the glutamate residue can be bonded through Cdelta (γ -linkage) as shown in formula (3b) when m is 2 and n is 1 (claim 27), which reads on
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(R3) of instant claims 1 and 25.
Regarding claims 42 and 43, Benesova discloses that DOTA can be bound by radiometal such as 177Lu (page 33, ¶ 3).
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 1-3, 12, 15, 25, 30, 31, 35, 40, 42, 43, and 46-48 are rejected under 35 U.S.C. 103 as being unpatentable over Benesova et al. (WO 2018 215627; cited on IDS filed November 21, 2023) in view of Anderson et al. (Bioorganic and Medicinal Chemistry, 2007; cited on PTO-892).
As discussed above, regarding claims 1, 2, 12, 15, 25, 30, 31, 35, and 40, Benesova discloses a compound comprising a chelating agent, a prostate specific membrane antigen (PSMA)-binding entity, and an albumin-binding entity connected via suitable linkers and spacers for use as diagnostic and/or therapeutic radiopharmaceuticals (page 1, ¶ 1). Benesova discloses a compound of General Formula (7b) shown in claim 25, which reads on the Formula I-a of instant claim 1 when R1 is I in para position; R2 is H; n is 1; V is N; D is 1,4,7,10-tetraazacyclododecane-1 ,4,7,10-tetraacetic acid (DOTA); and a is 4. Benesova discloses that the amino acid residue (A) can be glutamate (claim 26). Benesova discloses that the glutamate residue can be bonded through Cdelta (γ -linkage) as shown in formula (3b) when m is 2 and n is 1 (claim 27), which reads on
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(R3) of instant claims 1 and 25. Regarding claim 3, Benesova discloses a compound of General Formula (7b) shown in claim 25, which reads on the Formula I-b of instant claims 1 and 3 when R1 is I in para position; R2 is H; n is 1; V is CH2NH; D is DOTA; and a is 0. Benesova discloses that the A can be glutamate (claim 26) and the glutamate residue can be bonded through Cdelta (γ-linkage) as shown in formula (3b) when m is 2 and n is 1 (claim 27), which reads on
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(R3) of instant claims 1 and 25. Regarding claims 42 and 43, Benesova discloses that DOTA can be bound by radiometal such as 177Lu (page 33, ¶ 3).
Regarding claims 46-48, Benesova does not disclose the glutamate residue (R3) is linked through an α-peptide bond,
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as shown in instant claims 1, 25, and 46.
Anderson discloses that substrate specificity of PSMA is dependent on the chemical structure of the substrate (abstract). Anderson discloses that binding affinity and metabolic stability vary between the compounds comprising α-linked and γ-linked glutamate residues (page 6680, para 2, ¶ 1; page 6680, Figure 5).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the compound of Benesova by substituting γ -linked glutamate with α-linked glutamate to optimize binding affinity and stability of the compound. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Anderson teaches that glutamate can be linked through α-peptide bond and the pharmacokinetic properties can be different depending on the linkage type. The structural difference between Benesova and instant claims 46-48 (elected species of 177Lu-HTKO1169) is merely the point of attachment on the same glutamate residue. This is a common structural modification used in medicinal chemistry to adjust the stability, flexibility, orientation, and fit of a ligand within a binding pocket. Glutamate provides only two available carboxyl groups for peptide bonding (α and γ). Choosing between these two attachment points represents a selection from a finite number of identified, predictable solutions to investigate improved pharmacokinetic variables. Further, a person of ordinary skill in the art would have been motivated to utilize the standard synthesis method of the α-linked version in order to improve synthetic yield and reduce production cost for industrial drug development. Accordingly, Benesova in view of Anderson renders instant claims 46-48 (177Lu-HTKO1169) obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 12, 15, 25, 30, 31, 35, 40, 42, 43, and 46-48 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 13 of U.S. Patent No. US 11,504,441 (cited on IDS filed November 21, 2023) in view of Benesova et al. (WO 2018 215627; cited on IDS filed November 21, 2023).
Claim 1 of the ‘441 recites a compound of Formula II, which is structurally similar to the compounds of instant claims 1 and 46 when R2 is CH2; R6 is H; R7 is
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; R10 is
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(9-anthrylmethyl group); R12 is I in para position; and R11 is
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. Claim 13 of the ‘441 recites that Rx can be DOTA and chelated with 177Lu.
Claims of the ‘441 do not recite
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(2-naphthylmethyl group, R1 of instant claim1) at the R10 position.
As discussed above, Benesova discloses a compound comprising a chelating agent, a prostate specific membrane antigen (PSMA)-binding entity, and an albumin-binding entity connected via suitable linkers and spacers for use as diagnostic and/or therapeutic radiopharmaceuticals (page 1, ¶ 1). Benesova discloses the structure of Formula (7b), which has a 2-naphthylmethyl group at the same position (claim 25).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the compound of the ‘441 by substituting the 9-anthrylmethyl group at the R10 position with the 2-naphthylmethyl group. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Benesova teaches that 2-naphthylmethyl group can be incorporated into the compound at that exact position. The naphthalene and anthracene are members of a homologous series of polycyclic aromatic hydrocarbons and transitioning between a tricyclic (anthracene) and a bicyclic (naphthalene) system represents a routine reduction or extension of the aromatic core. Furthermore, moving a substitution from the 2-position to the 9-position is a regioisomeric variation that a person of ordinary skill in the art would employ to optimize structural interactions, modulate lipophilicity, and manage steric bulk.
Regarding the -CH2- linkers, claim 1 of the ‘441 recites that R2 can be -CH2- or -(CH2)3-, whereas instant claim recites a length of -(CH2)2-. Similarly, Formula I-b of instant claims 1 and 3 includes an additional -(CH2)1-4- connected to -R3- and no -CH2- connected to -NH-R4 compared to the Formula II of the ‘441. The length of the linker (-CH2-) is a matter of routine optimization and is therefore obvious. Compounds which are positional isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties (MPEP § 2144.09).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONG HWAN BAEK whose telephone number is (571)272-0670. The examiner can normally be reached Mon - Thu, 9 am - 3 pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
Prosecution Insights