DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 20 January 2026 has been entered.
This Office Action is in response to Applicant’s Amendment and Remarks filed on 20 January 2026 in which claims 40 and 42-44 were canceled, claims 1, 29, 34, and 39 were amended to change the scope and breadth of the claims, and claims 45-54 were newly added.
Claims 1, 27, 29, 33-34, 38-39 and 45-54 are pending in the current application and are examined on the merits herein.
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 .
Response to Arguments
Applicant's arguments filed 20 January 2026 have been fully considered but they are not persuasive.
The claims as amended are not commensurate in scope with the evidence of record. There is no evidence to support the administration of a combination using 20 nCi [Ac]-FPI-1434 that “results in a decrease in tumor volume relative to the tumor volume before or at the beginning of treatment”.
Furthermore, the scope of treating the cancers presently claimed wherein “administering results in a decrease in tumor volume relative to the tumor volume before or at the beginning of treatment” is unpredictable.
A table summarizing the experiments and prior art is provided:
Evidence
Radioconjugate or Radiotherapy
ATRi OR PARP
Tumor
Dosing Schedule
Tumor volume decrease?
Cuthbertson (fig. 22)
MSLN- TTC
BAY1895344
(ATRi)
Ovarian
N/A
No
Cuthbertson
(fig. 23)
MSLN-TTC
BAY1895344
Breast
N/A
No
Senra
Radiation
Olaparib
(PPAR)
Lung
N/A
No
Burak
[Ac]-FPI-1434
Colon
N/A
Yes
Burak
[Ac]-FPI-1434
Prostate
N/A
Yes
Burak
[Ac]-FPI-1434
Lung
N/A
No
Present Example 1
[Ac]-FPI-1434
BAY1895344
Colorectal
Schedule 1, fig. 1
No
Example 1
[Ac]-FPI-1434
BAY1895344
NSLC
Schedule 1; figure 1
No
Example 2
[Ac]-FPI-1434
50 nCi
BAY1895344
40 mg/kg; 30 mg/kg; 20 mg/kg
Colorectal
Schedule 2; fig. 3
Yes
Example 4
[Ac]-FPI-1434
Olaparib
NSLC
Schedule 1; figure 7
No
Example 5
[Ac]-FPI-1434
50 nCi
Olaparib
50 mg/kg
Colorectal
Schedule 2; fig. 9
Yes
Example 6
[Ac]-FPI-1434
20 nCi
50 nCi
Olaparib:
25 mg/kg, 50 mg/kg
Colorectal
Fig. 13A, 13B
No
Example 6
[Ac]-FPI-1434
100 nCi
Olaparib
25 mg/kg, 50 mg/kg
Colorectal
Figure 13C
Yes
According to example 6, corresponding to figures 13A and 13B, when 20 nCi is administered, followed by olaparib, the tumor volume was not decreased relative to the tumor volume before or at the beginning of treatment, as required by claim 1.
Furthermore, the results are limited to the treatment of colorectal cancer. The additional teaching of Burak et al. supports the scope for also treating prostate cancer, “wherein said administering results in a decrease in tumor volume relative to the tumor volume before or at the beginning of treatment”.
The rejection below is hereby maintained.
Maintained Rejections
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 27, 29, 33, 34, 38-40 and 45-54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
With respect to the combination of radioimmunoconjugate and PARP inhibitor, the specification is enabled for decreasing tumor volume in a subject having colon cancer or prostate cancer, by administering to the mammal olaparib, wherein the mammal has received [225Ac]-FPI-1434, according to the dose and dosing schedule corresponding to figures 9 and 10; and according to the dose and dosing schedule of fig. 11 that corresponds to figure 13C, i.e. 50 nCi or 100 nCi [225Ac]-FPI-1434 and 25-50 mg/kg olaparib.
It does not reasonably provide enablement for decreasing tumor volume by following the method steps of claim 1, drawn towards decreasing tumor volume relative to the tumor volume before or at the beginning of treatment, wherein the radioimmunoconjugate is administered at a dose of 20-100 nCi and olaparib is administered at a dose of 25-50 mg/kg. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
(1) The nature of the invention: The nature of the invention is directed towards combination therapy of a radioimmunoconjugate and a PARP inhibitor. The nature of the invention was also directed towards identifying a dosage regiment and schedule that reduced tumor volume relative to the beginning of treatment.
(2) or (4) The state of the prior art/The predictability or unpredictability of the art:
Cuthbertson (WO2018153975, of record) demonstrates one of ordinary skill in the art would not have expected a decrease in tumor volume upon administration of a combination of a radioimmunoconjugate and PARP inhibitor. Figures 22 and 23 show that breast and ovarian tumor volumes of the combination therapy were significantly lower compared to each component administered alone. However, relative to the beginning of treatment, tumor volume either slightly increased or remained stable after treatment with a combination of Thorium-227 containing compound and an ATR inhibitor. In other words, tumor volumes did not decrease relative to the beginning of treatment.
Senra et al. (Mol. Cancer Ther, October 2011, vol. 10, no. 10, pp. 1949-1958, of record) is directed towards administering radiotherapy in combination with olaparib. Senra et al. found the combination slowed the growth of tumor volume relative to the vehicle, olaparib alone and radiation alone. However, relative to the beginning of treatment, lung tumor volume remained stable before increasing. In other words, lung tumor volumes did not decrease relative to the beginning of treatment.
Burak et al. (US 10,093,741, of record) further demonstrate the decrease in tumor volume may depend on the targeted tumor. The radioimmunoconjugate of Burak et al. is the same as presently claimed (see e.g. fig. 7). The compounds were tested for their ability to reduce tumor volume against colon cancer. It appears while they were effective in reducing tumor volume against colon cancer and prostate cancer, they were not effective in reducing tumor volume in lung cancer.
The relative skill of those in the art: The relative skill of those in the art is high, given the use of radioimmunoconjugates, including [225Ac] containing compounds and PARP inhibitors, including olaparib were known before the effective filing date of the claimed invention. In addition, the use of each of these therapies as part of a combination therapy were also was known before the effective filing date of the claimed invention.
(6) and (7) The amount of direction or guidance presented/The presence or absence of working examples:
[225Ac]-FPI-1434 = radioimmunoconjugate of claim 16, also referred to as “FPI-1434”
BAY-1895344 = aka elimusertib, an ATR inhibitor (DDRi), reads on present claim 34
Example 1 – dosing schedule 1 (fig. 1), combination therapy of 50 or 200 nCi [225Ac]-FPI-1434 and BAY-1895344, tested against colorectal cancer and NSCLC models. Combination groups were dosed with BAY-1895344 2 days on, 5 days off, using a 20 mg/kg dose for 28 days. The first dose of BAY-1895344 was administered 24 hours following [225Ac]-FPI-1434.
The specification states administration of BAY-1895344 alone did not demonstrate any reduction in tumor volume over time relative to vehicle controls. Treatment with [225Ac]-FPI-1434 alone demonstrated significant reduction in tumor volume relative to vehicle controls. There did not appear to be any additional benefit when [225Ac]-FPI-1434 and BAY-1895344 were administered as a combination therapy using the dosing schedule in Fig. 1.
With respect to relative terms like “decrease”, the specification teaches it has meanings relative to a reference level. “In some embodiments, the reference level is a level in the same subject before or at the beginning of treatment. In some embodiments, the reference level is the average level in a population not being treated by said method of treatment.”
Looking at figures 2A and 2B, while the tumor volume of the [225Ac]-FPI-1434 treated group was lower compared to a vehicle control at any given point after treatment initiation, the tumor volume is not (significantly) reduced compared to the level in the “same subject before or at the beginning of treatment”. Additionally, the tumor volume of the combination therapy treated group was not reduced compared to the level in the “same subject before or at the beginning of treatment”.
Example 2 – dosing schedule 2 (fig. 3), combination therapy of 50 nCi [225Ac]-FPI-1434 and BAY-1895344, tested against colorectal cancer. Combination groups were dosed with BAY-1895344 three times a week, starting with a 40 mg/kg dose. The dose was gradually reduced to 20 mg/kg. The first dose of BAY-1895344 was administered 24 hours following FP-1434 administration (fig. 3).
The specification states each agent alone demonstrated some reduction in tumor volume over time. Animals given the combination therapy using the dosing schedule in fig. 3, they demonstrated significantly lower tumor volumes when compared to either treatment alone.
Looking at figure 4, while the tumor volume of the [225Ac]-FPI-1434 treated group and BAY-1895344 treated group was lower compared to a vehicle control at any given point after treatment initiation, the tumor volume is not (significantly) reduced compared to the level in the “same subject before or at the beginning of treatment”. The tumor volume of the combination therapy treated group was reduced compared to the level in the “same subject before or at the beginning of treatment”.
Example 4 – dosing schedule 1 (fig. 7), combination therapy of 50 or 200 nCi [225Ac]-FPI-1434 and olaparib, tested against colorectal cancer and NSLC. The specification states the relative tumor volume was reduced when treated with FPI-1434, with no additional benefit when used in combination with olaparib. Combination groups were dosed with olaparib 5 days on, 2 days off, using a 50 mg/kg dose for 28 days. Animals were pre-dosed with olaparib 3 times prior to the FPI-1434 administration.
Looking at figures 8A and 8B, while the tumor volume of the [225Ac]-FPI-1434 treated group and BAY-1895344 treated group was lower compared to a vehicle control at any given point after treatment initiation, the tumor volume is not (significantly) reduced compared to the level in the “same subject before or at the beginning of treatment”. The tumor volume of the combination therapy treated group was not reduced compared to the level in the “same subject before or at the beginning of treatment”.
Example 5 – dosing schedule 2 (fig. 9), combination therapy of 50 nCi [225Ac]-FPI-1434 and Olaparib, tested against colorectal cancer. FPI-1434 was given as a single agent at 50 nCi. Combination groups were dosed with olaparib (i.p.) 5 days on, 2 days off, using a 50 mg/kg dose for 28 days. The first dose of olaparib was administered 24 hours following FPI-1434 administration.
The specification states the relative tumor volume was reduced when treated with either agent, with significantly lower tumor volumes for the combination therapy when compared to either treatment alone.
Looking at figure 10, while the tumor volume of the [225Ac]-FPI-1434 treated group and olaparib treated group was lower compared to a vehicle control at any given point after treatment initiation, the tumor volume is not (significantly) reduced compared to the level in the “same subject before or at the beginning of treatment”. The tumor volume of the combination therapy treated group was reduced compared to the level in the “same subject before or at the beginning of treatment”.
Example 6 – multiple dose levels of [225Ac]-FPI-1434 in combination with olaparib (fig. 11), tested against colorectal cancer. FPI-1434 was administered at a dose of 20 nCi, 50 nCi, or 100 nCi. Olaparib was administered at 25 mg/kg or 50 mg/kg. In combination groups, animals were dosed with olaparib starting at 24 hours after FPI-1434 administration according to a 5 days on, 2 days off schedule until day 30.
The specification states no therapeutic effect was observed with either agent alone. Animals that received the combination therapy demonstrated significantly lower tumor volumes when compared with animals that received either treatment alone.
Looking at fig. 13A and 13B, while the tumor volume of the [225Ac]-FPI-1434 treated group and olaparib treated group was lower compared to a vehicle control at any given point after treatment initiation, the tumor volume is not (significantly) reduced compared to the level in the “same subject before or at the beginning of treatment”.
Looking at fig. 13C, the tumor volume of the combination therapy treated group was reduced compared to the level in the “same subject before or at the beginning of treatment”.
The breadth of the claims:
The breadth of the claims includes treating any cancer, and wherein the radioimmunoconjugate is administered at a dose known not to result in a decrease in tumor volume relative to the tumor volume before or at the beginning of treatment.
(8) The quantity of experimentation necessary: The examples in the present Application, the teachings of Cuthbertson, and Senra all demonstrate the unpredictability in treating different tumors (colon cancer, prostate cancer, breast cancer, lung cancer, and ovarian cancer), decreasing tumor volume relative to the beginning of treatment using the combination of agents claimed.
In order to practice the invention with the full range of all possible treatment methods beyond those known in the art, one skilled in the art would undertake a novel and extensive research program to show that the current dosing regimen could be used to treat any cancer, wherein said administering results in a decrease in tumor volume relative to the tumor volume before or at the beginning of treatment.
There’s no evidence that 20 nCi [225Ac]-FPI-1434 in combination with olaparib, at the exemplified dosing schedule, and dose would decrease tumor volume relative to the beginning of treatment.
In order to determine the efficacy of the claimed therapies in the absence of any existing in vivo data, one skilled in the art would undertake animal testing in order to practice the invention. Animal experiments include, induction of the disease state, administration of the potential pharmaceutical combination and dosing schedules, and collection and analysis of data, additional burdens associated with compliance with animal welfare regulations, care, feeding and other maintenance of the animals, dissection of dead animals to collect data, and dispose of the dead animals after the research is finished. These trials would need to be run separately and repeatedly for each disorder to be treated, and success in treating each and every disorder would still not be definitive. The experimentation involved would therefore be significant, undue and unpredictable.
Genentech, 108 F.3d at 1366, sates that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the breadth of the claims, Applicants fail to provide information sufficient to practice the claimed invention for decreasing tumor volume by following the method steps of claims 1 and 34.
The above rejection can be overcome by amending claims 1 and 34 to a dose of radioimmunoconjugate to 50-100 nCi, and limiting the cancer to those recited in claims 29 and 39.
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, 27, 29, 33, 34, 38-40 and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 34-48 of copending Application No. 17/337,358 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are similarly directed towards a method of treating or ameliorating cancer, the method comprising administering to a mammal a DDRi, wherein the mammal has received or is receiving a radioimmunoconjugate. The radioimmunoconjugate of claim 34 of the reference application is the same as the structure in present claim 16.
The DDRi of the reference application is a PARP inhibitor, and includes olaparib (see claim 39 of the reference application).
The present claims are prima facie obvious over the claims of the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 11 June 2025 have been fully considered but they are not persuasive.
Applicant has requested that the provisional rejections be held in abeyance until patentable subject matter is identified.
No patentable subject matter has been identified.
The obviousness double patenting rejections are hereby maintained.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699