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 .
Drawings
The drawings are objected to because at least one drawing submitted in file is in color without granted petition to accept color drawings.
Appropriate correction is required.
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.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The abstract of the disclosure is objected to because it is too short in length (29 words). Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally be limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Appropriate correction is required.
The disclosure is objected to because of the following informalities:
The use of the terms Matrigel® and Vivo Manager® 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.
The disclosure is objected to because of the following informalities:
On page 9, ¶ 50, the structure of Formula (ii) contains formatting errors. It appears that all non-carbon atoms depicted by letters and associated charges are in a smaller text size and shifted from their intended positions.
In FIGs 2 and 3, a prominent black rectangular box is drawn vertically at approximately Day 42. However, the specification fails to provide any explanation, reference, or definition for what this black rectangular box represents. Every feature or annotation shown in the drawings must be described in the specification.
Appropriate correction is required.
Claim Objections
Claim 8 is objected to because of the following informalities:
Claim 8 recites “tumour,” whereas claim 1, from which claim 8 depends, recites “tumor.” Additionally, dependent claim 14 recites “tumor.” It is suggested that claim 8 be amended to maintain consistency with the spelling of “tumor.”
Appropriate correction is required.
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 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Osterkamp et al. (WO 2014 086499; cited on IDS filed March 1, 2024) in view of Conroy et al. (New England Journal of Medicine, 2011; cited on PTO-892).
Regarding claims 1, 8, 9, and 14, Osterkamp discloses a method for the treatment of disease comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound (page 73, ¶ 3). Osterkamp discloses that a neurotensin receptor 1 (NTR1) binding compound can be used for targeting tumors that highly express NTR1 such as pancreatic ductal adenocarcinoma (PDAC) (page 3, ¶ 3; page 5, ¶ 1). Regarding claims 2-4, 6, and 13, Osterkamp discloses that the compound can comprise a radionuclide such as 177Lu (beta-emitting radionuclide) and 225Ac (alpha-emitting radionuclide) (page 66, ¶ 4). Regarding claim5, Osterkamp discloses that the compound can have the structure of formula (IIia)
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, which reads on formula (i) of instant claim 5 (claim 12). Regarding claim 7, Osterkamp discloses that the compound of formula (IIia) can chelate a radionuclide such as 177Lu, which reads on formula (ii) of instant claim 7 (claim 13). Regarding claims 11 and 12, Osterkamp discloses that the compound comprising a radionuclide can be administered by any conventional route such as intravenous injection (page 81, ¶¶ 4-5). Osterkamp discloses that dosages employed in practicing the methods for treatment and diagnosis can vary depending on the particular condition to be treated (page 80, ¶ 4). Osterkamp discloses that the compound comprising a nuclide can be administered once (single dose) or at several times (multiple doses) (page 80, ¶ 4). Osterkamp discloses that the dose range of the compound comprising a radionuclide can be 1 to 200 MBq, 1 to 400 MBq, or 10 to 5000 MBq (0.01 to 5 GBq) depending on the radionuclide and the subject (page 80, ¶ 4; page 81, ¶ 1). Regarding claims 1 and 10, Osterkamp discloses that the treatment method of radiotherapy using the compound can be combined with other treatment methods including chemotherapy using antimetabolites or other antitumor agents (page 73, ¶ 4; page 80, ¶ 2).
Osterkamp does not disclose a combination comprising folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) and that the neurotensin receptor binding compound is administered in simultaneous, separate, or sequential combination with FOLFIRINOX. Regarding claim 15, Osterkamp does not disclose that the subject has metastatic PDAC and has not previously received a therapy for treating pancreatic cancer.
Conroy discloses that FOLFIRINOX can be used as first-line therapy in patients with metastatic pancreatic cancer (abstract). Conroy discloses that the FOLFIRINOX showed a survival advantage in patients having previously untreated metastatic pancreatic adenocarcinoma (abstract; page 1818, column 1, ¶ 3).
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 method of Osterkamp by utilizing FOLFIRINOX as first-line chemotherapy before radiotherapy using a radiolabeled NTR1 binding compound in order to treat a subject with untreated metastatic PDAC more effectively. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Conroy teaches that the FOLFIRINOX can be used for first-line chemotherapy in a patient with previously untreated metastatic pancreatic adenocarcinoma. Further, a person of ordinary skill in the art would have been motivated to utilize combined chemoradiotherapy in order to achieve synergistic tumor destruction, and systemic and local control. The radiation dose range in Osterkamp overlaps with that of instant claims. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. A dosing regimen including dose range and frequency is a clearly result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine a dosing regimen including dose range and frequency in order to achieve an optimal therapeutic dose for the patients. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See MPEP § 2144. Accordingly, applying the teachings of Conroy to the method of Osterkamp constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering instant claims 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 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/541,534 (US 2024 0216550; cited on PTO-892) in view of Conroy et al. (New England Journal of Medicine, 2011; cited on PTO-892).
Regarding claim 1, claim 1 of the ‘534 recites a method of treating a neurotensin receptor overexpressing tumor, comprising administering to a subject in need thereof a therapeutically effective amount of a combination comprising a neurotensin receptor binding compound, folinic acid, fluorouracil, and liposomal irinotecan. Regarding claims 2-4, 6 and 13, claim 6 of the ‘534 recites that the neurotensin receptor binding compound is radiolabeled with 225Ac. Regarding claim 5, claim 5 of the ‘534 recites that the neurotensin receptor binding compound comprises a molecule of formula (i)
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or a complex thereof. Regarding claim 7, Regarding claim 6, claim 7 of the ‘534 recites that he neurotensin receptor binding compound is a complex of formula (ii)
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. Regarding claims 8 and 14, claim 8 of the ‘534 recites that the neurotensin receptor overexpressing tumor can be PDAC. Regarding claim 9, claim 9 of the ‘534 recites that the neurotensin receptor binding compound is an NTR1 binding compound. Regarding claim 10, claim 10 of the ‘534 recites that the neurotensin receptor binding compound is administered in simultaneous, separate, or sequential combination with folinic acid, fluorouracil, and liposomal irinotecan. Regarding claim 11, claim 11 of the ‘534 recites that the radiolabeled neurotensin receptor binding compound is administered by injection IV at a dose of about 2 to 7 GBq per injection. Regarding claim 12, claim 12 of the ‘534 recites that the radiolabeled neurotensin receptor binding compound is administered as a unitary dosage of less than 40 MBq. Regarding claim 15, claim 15 of the ‘534 recites that the subject has metastatic PDAC and has not previously received a therapy for treating pancreatic cancer.
Claims of the ‘534 do not recite an irinotecan and oxaliplatin.
As discussed above, Conroy discloses that FOLFIRINOX comprising irinotecan and oxaliplatin can be used as first-line therapy in patients with metastatic pancreatic cancer (abstract). Conroy discloses that the FOLFIRINOX showed a survival advantage in patients having previously untreated metastatic pancreatic adenocarcinoma (abstract; page 1818, column 1, ¶ 3).
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 method of the ‘534 by utilizing irinotecan and oxaliplatin in order to treat patients more effectively. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Conroy teaches that FOLFIRINOX which comprises irinotecan and oxaliplatin can be used for first-line chemotherapy in a patient with previously untreated metastatic pancreatic adenocarcinoma. Further, a person of ordinary skill in the art would have been motivated to utilize a combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin in instead of a combination of folinic acid, fluorouracil, and liposomal irinotecan in order to achieve a greater synergistic antitumor effect by pairing a variety of drugs from different classes. A person of ordinary skill in the art would have been motivated to optimize such drug combinations of drugs based on specific cancer types and clinical conditions. Accordingly, applying the teachings of Conroy to the method of the ‘534 constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/541,604 (US 2024 0197927; cited on PTO-892) in view of Conroy et al. (New England Journal of Medicine, 2011; cited on PTO-892).
Regarding claim 1, claim 1 of the ‘604 recites a method of treating a neurotensin receptor overexpressing tumor, comprising administering to a subject in need thereof a therapeutically effective amount of a combination comprising a neurotensin receptor binding compound, gemcitabine and nab-paclitaxel. Regarding claims 2-4, 6, and 13, claim 6 of the ‘604 recites that the neurotensin receptor binding compound is radiolabeled with 225Ac. Regarding claim 5, claim 5 of the ‘534 recites that the neurotensin receptor binding compound comprises a molecule of formula (i)
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or a complex thereof. Regarding claim 7, Regarding claim 6, claim 7 of the ‘604 recites that he neurotensin receptor binding compound is a complex of formula (ii)
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. Regarding claims 8 and 14, claim 8 of the ‘604 recites that the neurotensin receptor overexpressing tumor can be PDAC. Regarding claim 9, claim 9 of the ‘604 recites that the neurotensin receptor binding compound is an NTR1 binding compound. Regarding claim 10, claim 10 of the ‘604 recites that the neurotensin receptor binding compound is administered in simultaneous, separate, or sequential combination with gemcitabine and nab-paclitaxel. Regarding claim 11, claim 14 of the ‘604 recites that the radiolabeled neurotensin receptor binding compound is administered by injection IV at a dose of about 2 to 7 GBq per injection. Regarding claim 12, claim 16 of the ‘604 recites that the radiolabeled neurotensin receptor binding compound is administered as a unitary dosage of less than 40 MBq.
Claims of the ‘604 do not recite FOLFIRINOX and the subject having metastatic PDAC and not having previously received a therapy for treating pancreatic cancer.
As discussed above, Conroy discloses that FOLFIRINOX can be used as first-line therapy in patients with metastatic pancreatic cancer (abstract). Conroy discloses that the FOLFIRINOX showed a survival advantage in patients having previously untreated metastatic pancreatic adenocarcinoma (abstract; page 1818, column 1, ¶ 3).
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 method of the ‘534 by utilizing FOLFIRINOX in order to treat patients having previously untreated metastatic PDAC more effectively. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Conroy teaches that FOLFIRINOX can be used for first-line chemotherapy in a patient with previously untreated metastatic pancreatic adenocarcinoma. Further, a person of ordinary skill in the art would have been motivated to utilize a combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin in instead of (or in addition to) a combination of gemcitabine and nab-paclitaxel in order to achieve a greater synergistic antitumor effect by pairing a variety of drugs from different classes. A person of ordinary skill in the art would have been motivated to optimize such drug combinations of drugs based on specific cancer types and patient conditions. Accordingly, applying the teachings of Conroy to the method of the ‘604 constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/541,618 (US 2024 0207455; cited on PTO-892) in view of Conroy et al. (New England Journal of Medicine, 2011; cited on PTO-892).
Regarding claim 1, claim 1 of the ‘618 recites a method of treating a neurotensin receptor overexpressing tumor, comprising administering to a subject in need thereof a therapeutically effective amount of a combination comprising a neurotensin receptor binding compound, folinic acid, fluorouracil, liposomal irinotecan, and oxaliplatin. Regarding claims 2-4, 6 and 13, claim 6 of the ‘618 recites that the neurotensin receptor binding compound is radiolabeled with 225Ac. Regarding claim 5, claim 5 of the ‘618 recites that the neurotensin receptor binding compound comprises a molecule of formula (i)
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or a complex thereof. Regarding claim 7, Regarding claim 6, claim 7 of the ‘618 recites that he neurotensin receptor binding compound is a complex of formula (ii)
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. Regarding claims 8 and 14, claim 8 of the ‘618 recites that the neurotensin receptor overexpressing tumor can be PDAC. Regarding claim 9, claim 9 of the ‘618 recites that the neurotensin receptor binding compound is an NTR1 binding compound. Regarding claim 10, claim 10 of the ‘618 recites that the neurotensin receptor binding compound is administered in simultaneous, separate, or sequential combination with folinic acid, fluorouracil, liposomal irinotecan, and oxaliplatin. Regarding claim 11, claim 11 of the ‘618 recites that the radiolabeled neurotensin receptor binding compound is administered by injection IV at a dose of about 2 to 7 GBq per injection. Regarding claim 12, claim 12 of the ‘618 recites that the radiolabeled neurotensin receptor binding compound is administered as a unitary dosage of less than 40 MBq. Regarding claim 15, claim 15 of the ‘618 recites that the subject has metastatic PDAC and has not previously received a therapy for treating pancreatic cancer.
Claims of the ‘618 do not recite an irinotecan.
As discussed above, Conroy discloses that FOLFIRINOX comprising irinotecan can be used as first-line therapy in patients with metastatic pancreatic cancer (abstract). Conroy discloses that the FOLFIRINOX showed a survival advantage in patients having previously untreated metastatic pancreatic adenocarcinoma (abstract; page 1818, column 1, ¶ 3).
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 method of the ‘618 by utilizing irinotecan in order to treat patients more effectively. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Conroy teaches that FOLFIRINOX which comprises irinotecan can be used for first-line chemotherapy in a patient with previously untreated metastatic pancreatic adenocarcinoma. Further, a person of ordinary skill in the art would have been motivated to utilize irinotecan in instead of liposomal irinotecan in order to achieve lower cost, simpler administration, and efficacy without carrier delays. A person of ordinary skill in the art would have been motivated to optimize such drug combinations of drugs based on specific cancer types and clinical conditions. Accordingly, applying the teachings of Conroy to the method of the ‘618 constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, and 6 of copending Application No. 18/833,848 (US 2025 0099633; cited on PTO-892) in view Osterkamp et al. (WO 2014 086499; cited on IDS filed March 1, 2024) and Conroy et al. (New England Journal of Medicine, 2011; cited on PTO-892).
Regarding claim 1, claim 1 of the ‘848 recites a method of treating cancer comprising administering to a mammal a radiopharmaceutical. Regarding claims 2-6 and 13, claim 3 of the ‘848 recites that radiopharmaceutical is an 225Ac-radiopharmaceutical comprising 225Ac chelated with the following structure
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. Regarding claim 7, claim 1 of the ‘848 recites that radiopharmaceutical comprises a radionuclide such as 177Lu chelated with a compound. Regarding claims 8 and 14, claim 16 of the ‘848 recites that the cancer can be PDAC. Regarding claim 12, claim 13 of the ‘848 recites that the 225Ac-radiopharmaceutical is administered as a unitary dosage of less than 15 MBq.
Claims of the ‘848 do not recite a neurotensin receptor overexpressing tumor, neurotensin receptor (or NTR1) binding compound, combination comprising FOLFIRINOX, and that the neurotensin receptor binding compound is administered in simultaneous, separate, or sequential combination with FOLFIRINOX. Claims of the ‘848 do not recite that administration by injection IV at a dose of about 2 to 7 GBq per injection, and that the subject having metastatic PDAC and not having previously received a therapy for treating pancreatic cancer.
As discussed above, Osterkamp discloses that the compound can have the structure of formula (IIia)
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, which is identical to the structure of compounds of instant claims and the ‘848. Osterkamp discloses that this compound is a NTR1 binding compound which can be used for targeting tumors that highly express NTR1 such as PDAC (page 3, ¶ 3; page 5, ¶ 1). Osterkamp discloses that the compound comprising a nuclide can be administered once or at several times with dose range of 10 to 5000 MBq (0.01 to 5 GBq) (page 80, ¶ 4; page 81, ¶ 1). Osterkamp discloses that the compound comprising a radionuclide can be administered by any conventional route such as intravenous injection (page 81, ¶¶ 4-5). Osterkamp discloses that the treatment method of radiotherapy using the compound can be combined with other treatment methods including chemotherapy using antimetabolites or other antitumor agents (page 73, ¶ 4; page 80, ¶ 2).
As discussed above, Conroy discloses that FOLFIRINOX can be used as first-line therapy in patients with metastatic pancreatic cancer (abstract). Conroy discloses that the FOLFIRINOX showed a survival advantage in patients having previously untreated metastatic pancreatic adenocarcinoma (abstract; page 1818, column 1, ¶ 3).
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 method of the ‘848 by utilizing FOLFIRINOX as first-line chemotherapy prior to radiotherapy utilizing a radiolabeled (177Lu) NTR1 binding compound by injection IV at a dose of 5 GBq in order to treat a patient with previously untreated metastatic PDAC more effectively. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Osterkamp teaches that the compound can be used as a NTR1 binding compound for targeting tumors that highly express NTR1 such as PDAC, and that the compound comprising a radionuclide can be administered once by injection IV at a dose of 5 GBq. Osterkamp also teaches that the treatment method of radiotherapy using the compound can be combined with chemotherapy and Conroy teaches that FOLFIRINOX can be used for first-line chemotherapy in a patient with previously untreated metastatic pancreatic adenocarcinoma. Further, a person of ordinary skill in the art would have been motivated to utilize combined chemoradiotherapy in order to achieve synergistic tumor destruction, and systemic and local control. The radiation dose range in Osterkamp overlaps with that of instant claims. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. A dosing regimen including dose range and frequency is a clearly result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine a dosing regimen including dose range and frequency in order to achieve an optimal therapeutic dose for the patients. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See MPEP § 2144. Accordingly, applying the teachings of Osterkamp and Conroy to the method of the ‘848 constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, and 6 of copending Application No. 18/833,849 (US 2025 0177581; cited on PTO-892) in view Osterkamp et al. (WO 2014 086499; cited on IDS filed March 1, 2024) and Conroy et al. (New England Journal of Medicine, 2011; cited on PTO-892).
Regarding claim 1, claim 1 of the ‘849 recites a method of treating cancer comprising administering to a mammal a radiopharmaceutical. Regarding claims 2-6 and 13, claim 3 of the ‘849 recites that radiopharmaceutical is an 225Ac-radiopharmaceutical comprising 225Ac chelated with the following structure
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. Regarding claim 7, claim 1 of the ‘849 recites that radiopharmaceutical comprises a radionuclide such as 177Lu chelated with a compound. Regarding claims 8 and 14, claim 22 of the ‘849 recites that the cancer can be PDAC. Regarding claim 12, claim 19 of the ‘849 recites that the 225Ac-radiopharmaceutical is administered as a unitary dosage of less than 15 MBq.
Claims of the ‘849 do not recite a neurotensin receptor overexpressing tumor, neurotensin receptor (or NTR1) binding compound, combination comprising FOLFIRINOX, and that the neurotensin receptor binding compound is administered in simultaneous, separate, or sequential combination with FOLFIRINOX. Claims of the ‘849 do not recite that administration by injection IV at a dose of about 2 to 7 GBq per injection, and that the subject having metastatic PDAC and not having previously received a therapy for treating pancreatic cancer.
As discussed above, Osterkamp discloses that the compound can have the structure of formula (IIia)
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, which is identical to the structure of compounds of instant claims and the ‘849. Osterkamp discloses that this compound is a NTR1 binding compound which can be used for targeting tumors that highly express NTR1 such as PDAC (page 3, ¶ 3; page 5, ¶ 1). Osterkamp discloses that the compound comprising a nuclide can be administered once or at several times with dose range of 10 to 5000 MBq (0.01 to 5 GBq) (page 80, ¶ 4; page 81, ¶ 1). Osterkamp discloses that the compound comprising a radionuclide can be administered by any conventional route such as intravenous injection (page 81, ¶¶ 4-5). Osterkamp discloses that the treatment method of radiotherapy using the compound can be combined with other treatment methods including chemotherapy using antimetabolites or other antitumor agents (page 73, ¶ 4; page 80, ¶ 2).
As discussed above, Conroy discloses that FOLFIRINOX can be used as first-line therapy in patients with metastatic pancreatic cancer (abstract). Conroy discloses that the FOLFIRINOX showed a survival advantage in patients having previously untreated metastatic pancreatic adenocarcinoma (abstract; page 1818, column 1, ¶ 3).
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 method of the ‘849 by utilizing FOLFIRINOX as first-line chemotherapy prior to radiotherapy utilizing a radiolabeled (177Lu) NTR1 binding compound by injection IV at a dose of 5 GBq in order to treat a patient with previously untreated metastatic PDAC more effectively. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Osterkamp teaches that the compound can be used as a NTR1 binding compound for targeting tumors that highly express NTR1 such as PDAC and that the compound comprising a radionuclide can be administered once by injection IV at a dose of 5 GBq. Conroy teaches that FOLFIRINOX can be used for first-line chemotherapy in a patient with previously untreated metastatic pancreatic adenocarcinoma. Further, a person of ordinary skill in the art would have been motivated to utilize combined chemoradiotherapy in order to achieve synergistic tumor destruction, and systemic and local control. The radiation dose range in Osterkamp overlaps with that of instant claim. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. A dosing regimen including dose range and frequency is a clearly result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine a dosing regimen including dose range and frequency in order to achieve an optimal therapeutic dose for the patients. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See MPEP § 2144. Accordingly, applying the teachings of Osterkamp and Conroy to the method of the ‘849 constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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