DETAILED ACTION
This Office action details a first action on the merits for the above referenced application No. Claims 71-99 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 .
Priority
This application is a 35 USC 111(a) filing that claims benefit under 35 USC 120 as a continuation of US application No. 17/051,037 filed on 27 Oct. 2020 (now US 12,128,115 B1) which is a 35 USC 371 National Stage filing of international application No. PCT/US2019/029102 filed on 25 Apr. 2019 and claims benefit under 35 USC 119(e) to US provisional application No. 62/663,671 filed on 27 Apr. 2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 22 Nov. 2024 has been considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 71-99 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
In claim 71, the recitation of “corresponding to formula Ib” is indefinite because corresponding generally means analogous or equivalent to form or comparable and so it is not clear if the compounds are limited to those of formula Ib or must merely be comparable to formula I. In addition, the recitation of R5 to R12 is indefinite because it is not clear if the recitation refers to a range that includes R6, R7, R8, R9, R10, and R11 or not and in the case of the latter R6, R7, R8, R9, R10, and R11 are undefined. Claims 72-99 depend to claim 71 and fall therewith. Dependent claims 73-74, 76, 78-79, 81, 85, 87, 89, 91, 93, 95, and 97-98 recite the R5 to R12.
In claims 94 and 95, the recitation of “(ALP)” is indefinite because it is not clear if it is a required limitation or merely an example. In addition, the meaning of ALP is unclear.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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) 71-89, 92-93, and 96-99 is/are rejected under 35 U.S.C. 102(a)(1),(2) as being anticipated by Johnson et al. (WO 2017/223565 A1; published 28 Dec. 2017; see IDS filed on 22 Nov. 2024).
Regarding claims 71-89, 92-93, and 96-99, Johnson et al. disclose the compound
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(Fig. 16A) and compounds PSC-C-MCR1
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(Figs 17, 22B, 22C). These compounds read on compounds of instant formula Ib
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wherein R5=R6=R7=R8=R9=R10=R11=R12=H; and Ra=L-X or H, X=MCR1 peptide, L=a hydrophobic and hydrophilic linking group comprising heteroatom substitutions in the aliphatic chain and comprises a mixture of hydrophilic and hydrophobic entities and comprises a PEGn wherein n=2 and the divalent metal is 203Pb or 212Pb.
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) 71-99 is/are rejected under 35 U.S.C. 103 as being unpatentable over Johnson et al. (WO 2017/223565 A1; published 28 Dec. 2017).
Johnson et al. teach as discussed above. Johnson et al. teach compositions and methods of treating melanoma (title). Johnson et al. melanoma targeting conjugate comprising formula I T-L-X wherein T=MCR1 ligand, L=linker, and X=anti-cancer composition wherein a suitable radionuclide is Pb-203 or Pb-212 and wherein L is a hydrophobic linker or a hydrophilic linker including heteroatom substitution optionally comprising a mixture of hydrophilic and hydrophobic entities or L is PEGn where n=2 or 4 or ALP linker of 2 to 4 carbons (see pgs. 2-3). Johnson et al. teach the following linkers
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(see Fig. 9). Johnson et al. teach that the PSC chelator improves radiolabeling of peptides and does not interfere with binding of peptides to receptors. Radiolabeling was nearly 90% in 10 min and 37oC (pg. 18). Johnson et al. teach an significant improvement in cellular internalization when the DOTA-VMT-MCR1 is modified to include PEG4 (pg. 44). This introduces Pb specific chelator combined with a click cyclized peptide (PSC-C-MCR1) to improve tumor:kidney ratio of radionuclide uptake 7-fold (pg. 46). The new Pb specific chelator improves radiolabeling efficiency for 203Pb/212Pb theranostics. The development of the PSC is based on the chemical principle that minimizing charge contributes significantly to stability and that charge neutral complex does not increase the risk of kidney retention (pgs. 50-51).
Johnson et al. do not exemplify a compound of instant formula 1b wherein L is a PEG4 and n is 4 or wherein L is aliphatic linking group of 2-4 carbons.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the conjugate compounds of Johnson et al. ([203/212Pb]PSC-C-MCR1) so the linker is a PEG4 linker or a aliphatic (ALP) linking group of 2-4 carbons as taught by Johnson et al. because those linkers would have been expected to provide equivalent linkers suitable for linking the PSC chelator and suitable use in treating cancer and optionally because the PEG linker would have been expected to advantageously enhance tumor to kidney ratios.
Claim(s) 71-99 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kruper, Jr. et al. (US 5,310,535; issued 10 May 1994; see IDS filed on 22 Nov. 2024), in view of Tworowska et al. (US 2019/0336623 A1; published 7 Nov. 2019; see IDS filed on 22 Nov. 2024) and Jamous et al. (Nucl. Med. Biol.; published 2014; see attached 892).
Kruper, Jr. et al. teach carboxamide modified polyamine chelators and radioactive complexes thereof for conjugation to antibodies (see title). The complexes can be used for therapeutic and/or diagnostic purposes (see abstract). Kruper Jr., et al. teach cancer (col. 1). The biological molecule refers to any protein, antibody, antibody fragment, etc (col. 3). Kruper, Jr et al. teach a linker spacer moiety covalently bonded to the chelator moiety (col. 3) and synthetic routes to add linker (col. 7). Metals include 212Pb and 67Cu (col. 4). Kruper, Jr. et al. compound 10a
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(col. 10). Kruper, Jr et al. teach radioactive neutral complexes (col. 3). The invention provides for tetraazomacrocycles wherein one or two of the carboxylates are replaced with carboxamides. These chelating agents form complexes that are kinetically inert. These chelates exhibit rapid whole-body clearance and in certain cases have lower propensity for uptake in the bode (col. 2). Kruper, Jr et al. teach the preparation of PA-DODADA-177Lu labeled Fa(ab’)2CC49 (examples 9-11).
Kruper Jr. et al. do not teach or exemplify a compound of instant formula Ib where Ra or one of R5-R12 is -L-X and L is absent or a linker is a PEG2-4 or C1-4 alkyl such that linker is hydrophilic or hydrophobic comprising a mixture of hydrophobic and hydrophilic entities and there is a heteroatom substitution in the aliphatic chain. Kruper Jr. et al. do not further exemplify a 203Pb, 212Pb, 64Cu, or 67Cu complex.
Tworowska et al. teach the treatment of cancer cells overexpressing somatostatin receptors using octreotide derivatives chelated to radioisotopes (see title). Tworowska et al. teach PEG
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(Fig. 4a) and alkyl
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(Fig. 4b) linkers. Tworowska et al. teach TCMC monoacid
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([0012]) and the compound
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(Fig. 6A). The linker may comprises a straight- or branched chain C1-C6 alkyl or a polyethylene glycol ([0023]). The cancer treating composition may be used in combination with radioisotopes such as 212Pb, 203Pb, and 64Cu and have high linear energy transfer and short path lengths ([0198], [0201], [0204]-[0206]). Tworowska et al. teach 203Pb labeling high radiochemical yields ([0240]) and stable chelation of 203Pb and 64Cu ([0247]). Kidney retention can be reduced by co-administration of positively charged amino acids ([0258]).
Jamous et al. teach PEG spacers of different length influence the biologic profile of bombesin-based radiolabeled antagonists (see title). Jamous et al. teach that the introduction of low molecular weight PET spacers leads to improved pharmacokinetics in particular to lower kidney uptake and short retention in the kidneys without causing loss of affinity (pg. 465]). Jamous et al. teach DOTA-PEG2-JMV594, DOTA-PEG4-JMC594, DOTA-PEG6-JMV594 and DOTA-PEG12-JMV594 (see Fig. 1). The presence of the PEG4 spacer in 177Lu-DOTA-PESIN led to an improved pharmacokinetic profiled accelerating washout from excretory organs such as the kidney (pg. 468). Important parameters such as hydrophilicity and length of the spacer may play an important role in pharmacokinetics of small molecules (pg. 469).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify compounds of Kruper et al. (10a, and PA-DODADA-177Lu labeled Fa(ab’)2CC49 and derivatives thereof for imaging and treating cancer) by replacing the NH2-Ph-Et attached to the acetate arm with a PEG2, PEG4, or C1-4 alkyl (hydrophilic or hydrophobic linkers having heteroatom substitutions in the aliphatic chain and comprising hydrophobic and hydrophilic entities) attached to the acetamide N or to the macrocycle C as taught by Kruper Jr., et al., Tworowska et al., or Jamous et al. because those linkers would have been expected to advantageously enable conjugates having an enhanced pharmacokinetic profile and/or optimize the distance between the peptide targeting agent and the chelator. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Kruper Jr. et al. so that the compound 10a further complexes 203Pb, 212Pb, 64Cu, or 67Cu as taught by Kruper Jr. et al., and Tworowska et al. because those radiometal complexes would have been expected to advantageously enable charge neutral complexes exhibiting low non-specific uptake and fast clearance while providing radiotherapy and diagnostic (theranostic) pairs.
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 71-99 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12,128,115 B2, in view of Tworowska et al. (US 2019/0336623 A1; published 7 Nov. 2019; see IDS filed on 22 Nov. 2024) and Jamous et al. (Nucl. Med. Biol.; published 2014; see attached 892).
Claims 1-7 of U.S. Patent No. 12,128,115 B2 claim methods of performing a chelation reaction and diagnosing and treating a disease such as cancer using a compound of formula Ia
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that gets chelated with a divalent metal wherein R5-R12 is H or L-X and Ra is H or -L-X wherein each L is a polyethylene glycol, an aliphatic chain or a peptide chain and wherein X is a peptide.
Claims 1-7 of U.S. Patent No. 12,128,115 B2 do not claim a divalent metal that is 203Pb, 212Pb, 64Cu, or 67Cu or claim PEG2, PEG4, or a C1-4 aliphatic linker such that the linker is hydrophilic or hydrophobic and comprising heteroatoms substitution in the aliphatic chain and a mixture of hydrophilic and hydrophobic entities.
Tworowska et al. teach as discussed above.
Jamous et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective to modify the compounds of claims 1-7 of U.S. Patent No. 12,128,115 B2 so that the divalent metal is one of 203Pb, 212Pb, 64Cu, or 67Cu as taught by Tworowska et al. because those radiometal complexes would have been expected to advantageously charge neutral complexes exhibit low non-specific uptake and fast clearance while providing radiotherapy and diagnostic (theranostic) pairs.
It would have been obvious to a person of ordinary skill in the art before the effective to further modify the compounds of claims 1-7 of U.S. Patent No. 12,128,115 B2 so that the linker is a PEG2, PEG4, or a C1-4 aliphatic linker such that the linker is hydrophilic or hydrophobic and comprising heteroatoms substitution in the aliphatic chain and a mixture of hydrophilic and hydrophobic entities as taught by Tworowska et al. and Jamous et al. because those linkers would have been expected to advantageously enable conjugates having an enhanced pharmacokinetic profile and/or optimize the distance between the peptide targeting agent and the chelator.
Claims 71-99 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,179,484 B2, in view of Tworowska et al. (US 2019/0336623 A1; published 7 Nov. 2019; see IDS filed on 22 Nov. 2024) and Jamous et al. (Nucl. Med. Biol.; published 2014; see attached 892).
Claims 1-4 of U.S. Patent No. 11,179,484 B2 claim 1 melanoma targeting conjugate of formula I
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wherein the radiolabel is Pb-212 or Pb-203.
Claims 1-4 of U.S. Patent No. 11,179,484 B2 claim PEG2, PEG4, or a C1-4 aliphatic linker such that the linker is hydrophilic or hydrophobic and comprising heteroatoms substitution in the aliphatic chain and a mixture of hydrophilic and hydrophobic entities.
Tworowska et al. teach as discussed above.
Jamous et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective to further modify the compounds of claims 1-4 of U.S. Patent No. 11,179,484 B2 so that the linker is a PEG2, PEG4, or a C1-4 aliphatic linker such that the linker is hydrophilic or hydrophobic and comprising heteroatoms substitution in the aliphatic chain and a mixture of hydrophilic and hydrophobic entities as taught by Tworowska et al. and Jamous et al. because those linkers would have been expected to advantageously enable conjugates having an enhanced pharmacokinetic profile and/or optimize the distance between the peptide targeting agent and the chelator.
Claims 71-99 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,576,987 B2, in view of Tworowska et al. (US 2019/0336623 A1; published 7 Nov. 2019; see IDS filed on 22 Nov. 2024) and Jamous et al. (Nucl. Med. Biol.; published 2014; see attached 892).
Claims 1-4 of U.S. Patent No. 11,576,987 B2 claim a conjugate comprising a MCR1 ligand, a PEG2 linker and Pb-chelator PSC wherein the conjugate has the formula
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and
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.
Claims 1-4 of U.S. Patent No. 11,576,987 B2 do not claim a divalent metal that is 203Pb, 212Pb, 64Cu, or 67Cu or claim PEG2, PEG4, or a C1-4 aliphatic linker such that the linker is hydrophilic or hydrophobic and comprising heteroatoms substitution in the aliphatic chain and a mixture of hydrophilic and hydrophobic entities.
Tworowska et al. teach as discussed above.
Jamous et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective to modify the compounds of claims 1-4 of U.S. Patent No. 11,576,987 B2 so that the divalent metal is one of 203Pb, 212Pb, 64Cu, or 67Cu as taught by Tworowska et al. because those radiometal complexes would have been expected to advantageously enable charge neutral complexes exhibiting low non-specific uptake and fast clearance while providing radiotherapy and diagnostic (theranostic) pairs.
It would have been obvious to a person of ordinary skill in the art before the effective to further modify the compounds of claims 1-4 of U.S. Patent No. 11,576,987 B2 so that the linker is a PEG2, PEG4, or a C1-4 aliphatic linker such that the linker is hydrophilic or hydrophobic and comprises heteroatoms substitution in the aliphatic chain and/or a mixture of hydrophilic and hydrophobic entities as taught by Tworowska et al. and Jamous et al. because those linkers would have been expected to advantageously enable conjugates having an enhanced pharmacokinetic profile and/or optimize the distance between the peptide targeting agent and the chelator.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST.
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618
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