DETAILED ACTION
This Office action details a final action on the merits for the above referenced application No. Claims 1, and 4-16 are pending in this application.
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 .
Status of Claims
Claims 1, 4, and 10-16 are amended. Claims 2-3 are cancelled.
Response to Amendment
The claim amendments filed on 13 Jul. 2026 have been entered.
Response to Arguments
In view of Applicants amendments, the rejection of claims 1 and 4-14 under 35 USC 112(b) as being indefinite for failing to particularly point out and distinctly claims the subject matter is withdrawn.
In view of Applicants amendments, the rejection of claims 14-16 under 35 USC 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends is withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1 and 4-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Valliant et al. (WO 2015/073575 A2; published 21 May 2015), in view of Jamous et al. (Nucl. Med. Biol.; published 2014) and Price et al. (Chem. Soc. Rev.; published 2014), in further view of Fleuren et al. (Mol. Oncol.; published 2014) for the reasons cited in the Office action filed on 12 Mar. 2026.
Valliant et al. teach residualizing linkers and uses thereof (see title). Valliant et al. teach a method of treating cancer the method including administering to a subject in need thereof a foregoing conjugate. Valliant et al. teach a method of radiation treatment planning, the method including administering to a subject in need thereof any of the foregoing conjugates or pharmaceutical compositions. Valliant teach a method of treating cancer the method comprising administering to a subject in need thereof a first dose of any of the foregoing conjugates in an amount effective for treatment planning followed by administering a second dose of any of the foregoing conjugates in a therapeutically effective amount. In a certain embodiment the first dose and the second dose are either the same or different. The cancer is a solid tumor cancer for example breast cancer, etc. The method further includes administering an antiproliferative agents and any of the forgoing conjugates or compositions and the antiproliferative are administered within 28 d of each other (see pgs. 17, 27). Valliant et al. teach polypeptide-linker-detection agent conjugates where the polypeptide may be an IgG. The antibodies may be human or humanized antibodies. The antibodies may be of any type (IgG) and class (IgG1) (see pgs. 31-33). Radioisotopes and radionuclides include 111In and 225Ac. Chelating agents include edta, etc (see pg. 35). Antiproliferative agents include immunomodulators (see pg. 41). Valliant et al. teach a conjugate of formula
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wherein a metal is chelated to the structure (see pg. 11, claim 156) and conjugates of formulas
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and
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wherein iodine is 123I, 124I, 125I or 131I (see pg. 9). These compounds read in part on a compound of instant formula I A-L1-(L2)n-B wherein A is an imaging moiety such as a chelating moiety, L1 is a C8 alkyl. Valliant et al. teach residualizing linkers designed to retain the label intracellularly after lysosomal degradation of the internalized polypeptide conjugate. Valliant et al. teach linkers of formula II wherein L1, L2, and L3 may be absent/C1-C6 alkyl/heteroalkyl, R6 and R7 may be L4-B where L4 is C1-C6 alkyl/heteroalkyl. The linker portion of the module may be any length or lipophilicity to allow for enhanced physiochemical properties and biological activity (see pg. 37).
Valliant et al. do not teach administering to the subject in need thereof an effective amount of a compound having the structure of formula I wherein the compound is
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.
Jamous et al. teach PEG spacers of different length influence the biological profile of bombesin based radiolabeled antagonists (see title). The introduction of low molecular weight polyethylene glycol may lead to improved pharmacokinetics, in particular to lower kidney uptake and short retention in the kidneys without causing loss of affinity (see pg. 465). Jamous et al. teach structural formulae of four conjugates: MJ1, MJ2
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, MJ3
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, and MJ4
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(see Fig. 1). The PEG spacers do not influence the absolute tumor uptake but the pharmacokinetics of the radiopeptides resulting in impressive tumor to kidney ratios (see pg. 468). The presence of the PEG4 spacer in 177Lu-DOTA-PESIN led to an improved pharmacokinetic profile accelerating the wash out from the excretory organs such as kidney and liver when compared to bombesin having alkyl spacers (see pg. 468). The derivatives having the PEG4 as spacer showed increased tumor to kidney ratios and faster background clearance compared to the one having a Gly-aminobenzoic acid as spacer (see pg. 469).
Price et al. teach matching chelator to radiometals for radiopharmaceuticals (see title). For therapy applications particle emitters such as 111In and 225Ac are being heavily investigated typically in conjunction with antibody vectors (immunoconjugates) or peptides (see pg. 260). Price et al. teach that DOTA is the primary workhorse chelator for radiometal chemistry, and is currently the gold standard for isotopes including 111In and 225Ac. Some common bifunctional DOTA derivatives use one of the carboxylic arms for the site of vector conjugation, effectively blocking one of the coordination arms. DOTAGA solves this problem by conjugating to vectors through the carbon backbone and side arm functionalization. This DOTA derivative retains its maximum potential denticity as well as the same thermodynamic stability and kinetic inertness as unadulterated DOTA (see pgs. 266-267).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the methods of Valliant et al. (methods of radiation treatment planning and radiation treatment wherein the method comprises administering to a subject in need thereof an effective amount a DOTA-linker-antibody complex such as a 111In or 225Ac complex) so that the compound is
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(antibody-PEG3-DOTAGA) as taught by Valliant et al., Jamous et al., and Price et al. because the PEG3 linker would have been expected to provide an equivalent antibody conjugate suitable for radiation treatment planning/radiation treatment advantageously exhibiting an accelerated excretion profile and fast background clearance and because the DOTAGA chelator would have been expected to advantageously enable chelation of radiotherapeutic metals including 111In and 225Ac such that conjugate to the targeting vector does not block one of the coordinating arms providing maximum potential denticity.
It would have been obvious to person of ordinary skill in the art to further modify the methods of Valliant et al. by further substituting the antibody of the obvious antibody-PEG3-DOTAGA complex with a human or humanized IgG antibody that does not specifically bind to IGF-1R as taught by Valliant et al.. because it would have been expected to provide an equivalent targeted antibody conjugate suitable for use in radiation treatment planning/radiation treatment. There would have been a reasonable expectation of success since Valliant et al. teach that the antibody may be a human or humanized IgG antibody of any type (IgG1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify Valliant et al. by further forming a 225Ac-DOTAGA-PEG3-human/humanized IgG antibody that does not bind specifically to IGF-1R and then administer an effective amount of that complex to a subject in need thereof optionally repeatedly (first and second doses that the same or different) as taught by Valliant et al. and Price et al. because it would have been expected to advantageously enable radiotherapy over time using a radionuclide well suited for delivering massive toxicity to target cells. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Valliant et al. by further administering an antiproliferative agent or an immunomodulatory agent optionally wherein the compound of formula I and the antiproliferative agent are administered within 28 d of each other or the compound and the immunomodulatory agent are administered within 90 d of each other as taught by Valliant et al. because it would have been expected to advantageously enable combination therapies with other agents. The time between treatments of the compound of formula I and the antiproliferative agent/immunomodulatory agent are result effective variables that a person of ordinary skill in the art would have been motivated to modify at the time of the invention. A person of ordinary skill in the art would have arrived at a time within 28 d for the antiproliferative agent and a time within 90 d for the immunomodulatory agent in order to achieve optimal combinatorial (a synergistic) effect.
Valliant et al. do not further teach that the compound of formula I in said first dose comprises 111In and the compound of formula I administered in said second dose comprises 225Ac or a progeny thereof.
Fleuren et al. teach theranostic applications of antibodies in oncology (see title). Fleuren et al. teach that antibody theranostics combine the diagnostic and therapeutic potential of an antibody thereby selecting those patients who are most likely to benefit from antibody treatment (see abstract). Fleuren et al. teach 111In-labeled antibodies for theranostic tests (see table 2). Fleuren et al. teach 111In-trastuzumab SPECT (IgG antibody that does not bind IGF-1R; see pg. 805). For 177-J591 and 90Y-J591 RIT selection, 111In-J591 imaging can be performed since distribution patterns are generally comparable (see pg. 808). 111In-girentuximab was used for diagnostic imaging, and only patients with visible CAAIX-targeting received high dose 177Lu-girentuximab (see pg. 808).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify the methods of Valliant et al. by further forming a 111In-DOTAGA-PEG3-IgG antibody complex that does not bind specifically to IGF-1R and then administer a first dose of that complex prior to administering the obvious 225Ac-DOTAGA-PEG3-IgG antibody complex that dose not bind specifically to IGF-1R for radiation treatment as taught by Fleuren et al. because it would have been expected to advantageously enable therapeutic applications wherein the first dose of the 111In-DOTAGA-PEG3 IgG antibody complex enables patient selection and monitoring.
Applicants Arguments
Applicants assert that Valliant is merely directed to conjugates including a residualizing linker. The structures described in Valliant differ significantly to the specific compounds of formula I recited in independent claim 1. The person of ordinary skill would have no reason to deviate from the explicit requirements of the genus structure of formula I of Valliant. Even if the person of ordinary skill in the art would have looked to Valliant’s formula I, they would have had to select either R6 or R7 to be L4-B and further select L4 to be absent. Applicants assert impermissible hindsight because it improperly deviates from the explicit requirement in Valliant to use compounds of genus formula I. Such modification would render Valliant unsatisfactory for its intended purpose by relying on a different structure beyond the scope defined by formula I. None of Jamous, Price, and/or Fleuren cure the deficiencies of Valliant. It is further submitted that Jamous does not teach a PEG3 linker at all. The skilled artisan would have only been led to add a PEG4 spacer group into the compounds of Valliant, which differ significantly in structure from the claimed compounds. Applicants assert unexpected results. None of the cited art documents disclose or suggest the technical effect of the claimed method which is to effectively eliminate radioactivity from the body after catabolism and/or metabolism. The claimed methods require radioimmunoconjugates including a combination of specific linkers and antibodies that unexpectedly reduces total radioactivity by increasing the excretion of the catabolic/metabolic products while maintaining the pharmacokinetics of the intact molecule which compared to known chelated conjugates. At instant example 7, compounds B and C resulted in distinctly different excretion routes and increased the amount of total excretion of radioactivity over a 7 d period. The improved excretion profile of compound B and C when conjugated to antibodies was general and reproducible effect. Applicants submit that the technical effect arises from the coordination properties of the DOTAGA chelator and its ability to form stable metal complexes rather than from any unique property of the specific radionuclide exemplified.
Applicant's arguments filed 13 Jul. 2026 have been fully considered but they are not persuasive. Valliant teaches and motivates all of a method of radiation treatment planning or radiation treatment comprising administering to a subject in need thereof an effective amount of an antibody conjugate wherein the antibody is a human or humanized IgG antibody or an antigen binding fragment thereof wherein the human or humanized IgG antibody does not specifically bind to IGF-1R and wherein the antibody conjugate is conjugated to a chelator and a radiometal such as 225Ac and 111In. Regarding the chelator, Valliant contemplates a wide range of chelating groups including but not limited to those listed on pg. 35. Regarding the linker, Valliant contemplates thousands of different linker moieties and Valliant teaches that the linkers should lead to conjugates having better target to non-target ratios. Regarding the claimed PEG3 linker, at pg. 9 Valliant teaches and motivates an antibody conjugate comprising the claimed PEG3 linker. Regarding the Valliant’s principle of operation, Valliant’s method operates to provide radiation treatment planning or radiation treatment by delivering a diagnostic and/or therapeutic radionuclide to target tissue by using an antibody targeting moiety wherein the antibody does not bind to IGF-1R. Regarding Applicants arguments that the claimed linkers differ structurally from the linkers of formula I in Valliant, the obviousness of the claimed linkers of the claimed antibody conjugates does not require that the linkers should be of the same general formula in Valliant or a primary reference. Instead, obviousness merely requires some teaching, suggestion or motivation in the prior art that would have led one of ordinary skill in the art to arrive at the claimed method of radiation treatment planning or radiation treating using the claimed linkers attached to DOTAGA with a reasonable expectation of success. Valliant was already in possession of the claimed PEG3 linker. Jamous teaches that pegylation effectively enhances the radiotherapeutic efficacy improving tumor targeting and prolonging tumor retention. In Jamous, the use of only a PEG linker resulted in higher tumor to kidney ratio and tumor to liver ratios, resulting in better candidates for therapeutic applications. Jamous teaches that the length of the PEG linker is important since the length can have an adverse effect on receptor-ligand complex stability. Price teaches that the DOTAGA chelating agent is advantageous in comparison to the DOTA chelating agent exemplified in Valliant since the DOTAGA chelating agent retains its maximum potential denticity while chelating the same radiometals including 111In and 225Ac. A recognized advantage is the strongest reason to combine. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify to method of radiation treatment planning and radiation treatment in Valliant so that the antibody conjugate uses only the PEG3 linker attached to DOTAGA chelator to arrive at the claimed compound because that method of radiation treatment planning or radiation treatment would have been expected to advantageously enable improved tumor targeting, prolonged tumor retention, optimal tumor to non-target ratios and optimal complex stability owing to maximal denticity. The modification of Valliant would not change the principle of operation of Valliant since the modification would have been expected to enable equivalent or better radiation treatment planning and radiation treatment. Regarding Applicants assertions of unexpected results, allegations of unexpected results must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. See In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). Jamous provides a method of radiation treatment planning wherein the method comprises administering to a subject in need thereof an effective amount of a compound comprising a peptide targeting moiety that does not bind to IGF-1R, a PEG2/4 linker, and a metal complex of a DOTA chelator and 177Lu. Regarding the claimed IgG antibody that does not bind to IGF-1R, applicant’s themselves assert that the alleged results are generalizable across targeting moieties. The examples in the specification do not comprise a comparison with the prior art of Jamous. Instead, the examples of the specification and declarations comprise a comparison with a conjugate attached to a DOTAGA chelator without a linker moiety but that is not what is taught in the cited prior art. Regarding the 40+ radiometals listed in claim 1, the examples in the specification and declarations only use the 177Lu radiometal with the DOTAGA chelator. While instant examples 8-10 describe the synthesis of 225Ac labeled compounds, none of those examples provide a radiochemical purity, radiochemical yield or specific activity suggesting that those examples are prophetic. The cited prior art of Price teaches that the chelator needs to be matched for the radiometal as some chelators are unsuitable for some metals due to at least stability issues. None of the specification examples or declarations suggest that all 40+ radiometals listed in claim 1 would enable unexpected results over the closest prior art.
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 and 4-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,093,741 B1, in view of Valliant et al. (WO 2015/073575 A2; published 21 May 2015), and Fleuren et al. (Mol. Oncol.; published 2014) for the reasons cited in the Office action filed on 12 Mar. 2026.
Claims 1-18 of U.S. Patent No. 10,093,741 B1 claim a compound comprising a structure
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wherein B is an antibody (AVE1642) and a method of treating cancer, the method comprising administering to a subject in need thereof an effective amount of the above compound in a pharmaceutically acceptable carrier wherein the cancer is a solid cancer or the cancer is breast cancer and wherein the method further comprises an antiproliferative agent, or radiation sensitizer or immunomodulatory agent and wherein the radionuclide is 225Ac or 111In.
Claims 1-18 of U.S. Patent No. 10,093,741 B1 do not claim a method wherein the antibody is a human/humanized antibody the does not specifically bind to IGF-1R. Claims 1-18 of U.S. Patent No. 10,093,741 B1 do not claim a method wherein the method comprises administering to a subject having cancer a first dose of the compound of formula I, followed by administering a second dose of the compound of formula I optionally wherein the first and second doses are the same or different optionally wherein the first dose is in an amount effective for treatment planning and the second is effective for radiation treatment optionally wherein the first dose comprises 111In or 225Ac and the second dose comprises 225Ac and optionally wherein the compound of formula I and the antiproliferative agent or immunomodulatory agent are administered within 28/90 d of each other.
Valliant et al. teach as discussed above.
Fleuren et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-18 of U.S. Patent No. 10,093,741 B1 so that B is a human or humanized antibody not binding specifically to IGF-1R as taught by Valliant et al. and Fleuren et al. because the antibody that does not bind specifically to IGF-1R would have been expected to provide an equivalent antibody conjugate suitable for use in radiation treatment planning/radiation treatment of cancers such as HER2 expressing cancers. There would have been a reasonable expectation of success since Valliant et al. teach that the antibody may be a human or humanized IgG antibody of any type (IgG1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-18 of U.S. Patent No. 10,093,741 B1 by administering a first dose of the obvious compound and a second dose of the obvious compound which is the same or different from dose optionally wherein the first dose is effective for treatment planning and the second dose is effective for radiation treatment and optionally wherein the first dose comprises 111In or 225Ac and the second dose comprises 225Ac as taught by Valliant et al. and Fleuren et al. because it would have been expected to advantageously enable treatment over time by repeated administration and/or treatment planning by imaging prior to radiation treatment. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-18 of U.S. Patent No. 10,093,741 B1 so that the compound and the antiproliferative agent are administered within 28 d of each other or so that the compound and the immunomodulator agent are administered within 90 d of each other as taught by Valliant et al. because it would have been expected to provide an equivalent method of treatment and/or advantageously enhanced treatment by a combinatorial effect.
Claims 1 and 4-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 11,433,148 B1, in view of Valliant et al. (WO 2015/073575 A2; published 21 May 2015), and Fleuren et al. (Mol. Oncol.; published 2014) for the reasons cited in the Office action filed on 12 Mar. 2026.
Claims 1-40 of U.S. Patent No. 11,433,148 B2 claim a compound of formula
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wherein the radionuclide is 225Ac or 111In and B is an antibody (AVE1642) and methods of treatment planning and/or radiation treatment comprising administering to a subject a diagnostically effective amount of the compound and/or administering a therapeutically effective amount of the compound optionally wherein the first dose and second dose are the same or different and wherein the cancer is solid and the cancer is a breast cancer optionally wherein the method comprises administering the compound and an antiproliferative agent within 28 d of each other or the compound and immunomodulatory agent within 90 d of each other.
Claims 1-40 of U.S. Patent No. 11,433,148 B2 do not claim a method wherein the antibody is a human/humanized IgG antibody that does not specifically bind to IGF-1R. Claims 1-40 of U.S. Patent No. 11,433,148 B2 do not claim a method wherein the compound of formula I administered in the first dose comprises 111In or 225Ac and the compound administered in the second dose comprises 225Ac.
Valliant et al. teach as discussed above.
Fleuren et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-40 of U.S. Patent No. 11,433,148 B2 so that the antibody is a human or humanized IgG antibody that does not specifically bind to IGF-1R as taught by Valliant et al. and Fleuren et al. because it would have been expected to provide an equivalent conjugate and method suitable for use in radiation treatment planning/radiation treatment including HER2 expressing cancers. There would have been a reasonable expectation of success since Valliant et al. teach that the antibody may be a human or humanized IgG antibody of any type (IgG1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-40 of U.S. Patent No. 11,433,148 B2 so that the obvious compound of formula (I) administered in the first dose comprises 111In or 225Ac and the obvious compound administered in the second dose comprises 225Ac as taught by Valliant et al. and Fleuren et al. because it would have been expected to advantageously enable radiotherapy over time (repeated doses) using a radionuclide well-suited for delivering massive toxicity to target cells and/or radiation treatment planning by imaging followed by radiotherapy (theranostic applications).
Claims 1 and 4-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,191,854 B1, in view of Valliant et al. (WO 2015/073575 A2; published 21 May 2015), and Fleuren et al. (Mol. Oncol.; published 2014) for the reasons cited in the Office action filed on 12 Mar. 2026.
Claims 1-16 of U.S. Patent No. 11,191,854 B2 claim a compound of formula A-L1-(L2)n-B wherein the compound is selected from
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and wherein B is a human or humanized IgG antibody or an antigen binding fragment thereof and wherein the metal of the metal complex is 177Lu or 225Ac and a pharmaceutical composition comprising a compound thereof.
Claims 1-16 of U.S. Patent No. 11,191,854 B2 do not claim the instant method of radiation treatment planning or radiation treatment comprising administering to a subject in need thereof an effective amount of the formula I wherein B is a human or humanized IgG antibody that does not specifically bind to IGF-1R optionally wherein the method comprises administering to a subject a first dose of formula I followed by a second dose of formula I optionally wherein the first and second dose are the same or different and effective for radiation treatment and wherein the cancer is a solid tumor such as a breast cancer and optionally the method further comprising administering an antiproliferative agent within 28 d of each other or an immunomodulatory agent within 90 d of each other and optionally wherein the first dose is 111In or 225Ac and the second dose is 225Ac.
Valliant et al. teach as discussed above.
Fleuren et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-16 of U.S. Patent No. 11,191,854 B2 so that B is a human or humanized antibody not binding specifically to IGF-1R as taught by Valliant et al. and Fleuren et al. because the antibody that does not bind specifically to IGF-1R would have been expected to provide an equivalent antibody conjugate suitable for use in radiation treatment planning/radiation treatment of cancers such as HER2 expressing cancers. There would have been a reasonable expectation of success since Valliant et al. teach that the antibody may be a human or humanized IgG antibody of any type (IgG1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-16 of U.S. Patent No. 11,191,854 B2 by administering a first dose of the obvious compound and a second dose of the obvious compound which is the same or different from dose optionally wherein the first dose is effective for treatment planning and the second dose is effective for radiation treatment and optionally wherein the first dose comprises 111In or 225Ac and the second dose comprises 225Ac as taught by Valliant et al. and Fleuren et al. because it would have been expected to advantageously enable treatment over time by repeated administration and/or treatment planning by imaging prior to radiation treatment. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-16 of U.S. Patent No. 11,191,854 B2 so that the compound and the antiproliferative agent are administered within 28 d of each other or so that the compound and the immunomodulator agent are administered within 90 d of each other as taught by Valliant et al. because it would have been expected to provide an equivalent method of treatment and/or advantageously enhanced treatment by a combinatorial effect.
Applicants Arguments
Applicants assert that the ‘741 and ‘148 patents require antibodies that bind to IGF-1R specifically and with high affinity. In contrast the claimed method specifies compounds where the human or humanized IgG antibody does not specifically bind to IGF-1R. There can be no permissible reason to modify those patents to have an antibody that does not bind to IGF-1R. Regarding the ‘854 patent, the instant application is a divisional application drawn to claims of a method of radiation treatment. In contrast the claims of the ‘854 patent, the claimed methods specify a human or humanized IgG antibody that does not specifically bind to IGF-1R. Valliant and Fleuren provide
Applicant's arguments filed 13 Jul. 2026 have been fully considered but they are not persuasive. Regarding Applicants arguments that the instant application is a divisional of the ‘854 patent, it is noted that the claims of instant application differ from the claims of the ‘854 patent mainly because the claims of instant application require that the IgG antibody does not bind to IGF-1R. In other words, the claims of the instant application are not consonant with restriction requirement made by the Examiner. Regarding the substitution of targeting moieties from an IgG antibody that binds to IGF-1R to an IgG antibody that does not bind to IGF-1R, Applicants own arguments assert that the alleged unexpected results are generalizable across targeting moieties. Valliant and Fleuren provide adequate reason and motivation to modify the claims of the ‘741, ‘148, and ‘854 patents so that the IgG antibody that binds to IGF-1R is substituted to an IgG antibody that does not bind to IGF-1R. A person of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to provide an equivalent antibody conjugate suitable for treating cancers such as HER2 expressing cancers and method of radiation treatment (planning) of cancer such as HER2 expressing cancers.
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.
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/SEAN R. DONOHUE/
Examiner, Art Unit 1618
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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