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 .
Claims and Previous Objections/Rejections Status
Claims 21-40 are pending in the application. Claims 1-20 are cancelled and claims 21-40 newly added in the amendment filed 2/11/26.
Any objections and/or rejections from previous office actions that have not been reiterated in this office action are obviated.
Response to Arguments
Applicant’s arguments, see Remarks, filed 2/11/26, with respect to the rejection(s) of claim(s) 1-20 under 35 U.S.C. 103 have been fully considered and are persuasive due to the cancellation of the claims 1-20 and to the statement that the other authors besides Dufort, Verry, Leduc and Tillement of Lux et al. (Br. J. Radiol. 2019; 92: 20180365, p1-20) are not inventors of the claimed subject matter. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of NCT02820454 (6/28/2016), Luchette et al. (Nanomed: Nanotechnol. Biol. Med. 10 (2014) 1751-1755) and Mignot et al. (Chem. Eur. J. 2013, 19, 6122-6136) and in further view of Berbeco et al. (WO2018/107057A1).
New Grounds of Rejection
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.
Claim(s) 21-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over NCT02820454 (6/28/2016) in view of Luchette et al. (Nanomed: Nanotechnol. Biol. Med. 10 (2014) 1751-1755) and Mignot et al. (Chem. Eur. J. 2013, 19, 6122-6136) and in further view of Berbeco et al. (WO2018/107057A1).
NCT02820454 (6/28/2016) discloses the method of treating brain metastases using AGuIX polysiloxane gadolinium-chelate nanoparticles via radiosensitization (Study Details, Brief title; Conditions).
The method of treating brain metastases comprises a single intravenous injection of AGuIX to a patient and subsequent whole brain radiation therapy starting 4 hours after AGuIX injection, up to 2 weeks (Study Description, Detailed Description) that encompasses the method of treating brain metastases and intravenous injection of the instant claims 21 and 25.
The whole brain radiation therapy encompasses the whole brain radiation therapy of the instant claim 33.
The radiation therapy comprises 30Gy 10 sessions of 3 Gy (Study Description, Detailed
Description; Arms and Interventions, Radiation: whole brain radiation therapy) that encompasses the
total dose of ionizing radiation and about 3 Gy per fraction in a maximum of 10 fraction of the instant
claims 34-36.
The secondary brain metastases are from histologically confirmed solid tumor (Eligibility, Criteria) that encompasses the solid tumor of instant claim 21.
An MRI scan is performed 2 hours after injection to visualize the distribution of AGuIX in brain metastases and surrounding healthy tissue (Study Description, Detailed Description) that encompasses imaging the brain metastases via MRI of the instant claim 40.
NCT02820454 (6/28/2016) does not disclose an injectable solution at a concentration between 50 and 150 mg/mL, 80 and 120 mg/mL or about 100 mg/mL of the instant claims 27-29.
NCT02820454 (6/28/2016) further discloses five does escalation cohorts include 15 mg/kg, 30 mg/kg, 50 mg/kg, 75 mg/kg and 100 mg/kg (Arms and Interventions). The patients are treated at sequentially rising dose levels of AGuIX (Study Description, Detailed Description).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare an injectable solution having concentration between 50 and 150 mg/mL, 80 and 120 mg/mL or about 100 mg/mL by varying and/or optimizing the AGuIX nanoparticles injectable solution concentration to provide the therapeutically effective doses for administration, according to the guidance provided by NCT02820454 (6/28/2016), to provide a composition having the desired concentration of therapeutically effective injected doses to determine the dose limiting toxicities and maximum tolerated dose that advantageously yields the greatest radioenhancing effect at the site of the tumor. It is noted that “[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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
NCT02820454 (6/28/2016) does not explicitly disclose that AGuIX nanoparticles comprise a
polysiloxane shell bound to Gd-DOTAGA chelating agents having a hydrodynamic diameter between 2 and 6 nm or lyophilized AGuIX nanoparticles contained in a pre-filled vial.
Luchette et al. (Nanomed: Nanotechnol. Biol. Med. 10 (2014) 1751-1755) discloses gadolinium-
based AGuIX nanoparticles (abstract). The AGuIX comprise dehydrated, spherical, sub 5-nm gadolinium particles consisting of gadolinium atoms attached to a polysiloxane shell via DOTAGA chelating agents (p1752, Gadolinium nanoparticles) that encompass the
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of the instant claims.
The sub 5-nm gadolinium particles encompass the hydrodynamic diameter comprised between 2 and 6 nm of the instant claim 21.
Luchette et al. further discloses that the AGuIX nanoparticles are rehydrated in sterile DEPC treated water (p1752, Gadolinium nanoparticles) for use in the method of treating tumor cells via radiation dose enhancement (abstract).
The dehydrated and rehydrated AGuIX nanoparticles were obtained from Nano-H and the rehydrated nanoparticles stored at 4°C (p1752, Gadolinium nanoparticles) that encompass the lyophilized powder gadolinium-chelated polysiloxane nanoparticles in a pre-filled vial to be reconstituted in an aqueous solution of the instant claim 26.
The method involves incubating cells with 0.5 mM AGuIX nanoparticles for one hour and the cells irradiated (6MV) on a clinical linear accelerator (Varian Medical Systems). The energy was selected because in vivo experiments are performed at the same energy (p1752, Inductively couple plasma-mass
spectroscopy and Irradiation step).
Mignot et al. (Chem. Eur. J. 2013, 19, 6122-6136) discloses 5 nm particles comprising polysiloxane matrix with DOTAGA-Gd3+ chelates on the surface (abstract) that encompass the
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of the instant claims.
The 5-nm gadolinium particles encompass the hydrodynamic diameter comprised between 2 and 6 nm of the instant claim 21.
The particles are freeze-dried for storage and can be dispersed again in water before use (p6125, right column, first full paragraph; p6134, Purification) that encompass the lyophilized powder gadolinium-chelated polysiloxane nanoparticles in a pre-filled vial to be reconstituted in an aqueous solution of the instant claim 26.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the AGuIX of NCT02820454 (6/28/2016) comprises the structure polysiloxane shell bound to Gd-DOTAGA chelating agents of Luchette et al. and/or Mignot et al. and will be of the size of 5-nm as the AGuIX of NCT02820454 is analogous to the AGuIX of Luchette et al. and/or Mignot et al.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to store the lyophilized AGuIX powder of NCT02820454 (6/28/2016) in a pre-filled vial for the advantage of storage and for further reconstitution in water prior to administration as the standard taught by Luchette et al. and/or Mignot et al.
NCT02820454 (6/28/2016) does not explicitly disclose number of Gd-DOTAGA chelates are between 5 and 50 or 5 and 20 of the instant claims 21 and 24.
Mignot et al. further discloses
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(Figure 1) wherein the polysiloxane core is surrounded by five individual Gd atoms (p6127, left column, first paragraph). The particles contain around 1.5 DOTAGA per Gd (Table 2; p6128, left column, last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the AGuIX of NCT02820454 (6/28/2016) comprises at least 5 Gd-NODAGA moieties as Mignot et al. envisioned at least 5 Gd atoms surround the polysiloxane core and 1.5 DOTAGA per Gd in the particles to yield particles with very low toxicity and efficiency as MRI agents and sensitizing agents for image-guided radiotherapy.
NCT02820454 (6/28/2016) does not disclose a second therapeutically effective amount between 50 and 150 mg/kg, 80 and 120 mg/kg or about 100 mg/kg of the instant claims 30-32, injecting the AGuIX within a period of between 2 and 7 days prior to first irradiation or injecting a second
therapeutically effective amount within period of 1 hour to 12 hours.
NCT02820454 (6/28/2016) discloses five does escalation cohorts include 15 mg/kg, 30 mg/kg, 50 mg/kg, 75 mg/kg and 100 mg/kg as that stated above.
Berbeco et al. (WO2018/107057A1) discloses the method of treating cancer (e.g. radiosensitizing a cancer in a subject) with high atomic number containing nanoparticles in combination with ionizing radiation (abstract; p13, lines 10-11 and 22; claims 19,21,22).
The nanoparticles of size from about 3 nm to about 6 nm comprise Bi/Gd-NODAGA covalently bound to a polysiloxane core (p2; p4, lines 1-3; p14; p16, lines 8-10 and 12-13; p19, lines 20-28; claims
3,5,9; Figure 1B).
The method of treating a tumor involves administering (i.e. intravenous) to the subject a therapeutically effective amount of the nanoparticles and waiting a sufficient time to allow the nanoparticles to accumulate in a cell or tissue associated with the cancer (p4, lines 4-5; p27, lines 21-30; p30, lines 20-21). The time sufficient to allow the nanoparticles to accumulate in a cell or tissue is from about 30 seconds to about 24 hours (p28, lines 1-13).
The method of treating a tumor involves administering one or more doses of radiation to the subject (p4, lines 4-10; p20, lines 1-5; p25, lines 14-18; claim 19) after the accumulation of the nanoparticles in a cell or tissue associated with the cancer. The cells are irradiated with a 6MV Varian
Truebeam® machine (p34, lines 22-23; p36, lines 7-9).
The individual steps of administering a therapeutically effective amount of the nanoparticles and/or administering one or more doses of radiation may be repeated multiple times (e.g. two times, three times, etc.) (p26, lines 9-13).
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to allow the first injection of AGuIX nanoparticles to accumulate in a cell or tissue for about 2 days as Berbeco et al. teaches that that time sufficient to allow the nanoparticles to accumulate in a cell or tissue is from about 30 seconds to about 24 hours and therefore, it would have been predictable to one of ordinary skill in the art to examine the extended incubation of the first injection of AGuIX nanoparticles for at least 2 days for determining the greatest accumulation of the radiosensitizer in the tumor cells or tissue prior to irradiation.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to allow the second injection of AGuIX nanoparticles to accumulate in a cell or tissue between 1 hour to 12 hours as Berbeco et al. teaches multiple administrations of the nanoparticles prior to irradiation and to allow a sufficient amount of time to allow the nanoparticles to accumulate in a cell or tissue is from about 30 seconds to about 24 hours and therefore, it would have been predictable to one of ordinary skill in the art to examine the incubation of the second injection of AGuIX nanoparticles for between 1-12 hours for determining the greatest accumulation of the radiosensitizer in the tumor cells or tissue prior to irradiation.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to examine the doses of NCT02820454 (6/28/2016) for the second injection of the AGuIX nanoparticle to determine the dose limiting toxicities and maximum tolerated dose that advantageously yields the greatest radioenhancing effect at the site of the tumor.
NCT02820454 (6/28/2016) does not disclose injecting a third therapeutically effective amount within 5 to 10 days or within 7 days after the first injection.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to inject a third dose of AGuIX nanoparticles to accumulate in a cell or tissue within 5 to 10 or 7 days after the first injection as Berbeco et al. teaches multiple administrations of the nanoparticles prior to irradiation and to allow a sufficient amount of time to allow the nanoparticles to accumulate in a cell or tissue prior to and/or after irradiation. Therefore, it would have been predictable to one of ordinary skill in the art to examine the incubation of a third injection of AGuIX nanoparticles to determine the greatest accumulation of the radiosensitizer in the tumor cells or tissue prior to irradiation for the advantage of providing the greatest radioenhancing effect at the site of the tumor.
NCT02820454 (6/28/2016) does not disclose that the solid primary cancer is a primary melanoma, lung cancer, breast cancer, kidney cancer or colon cancer.
Berbeco et al. further discloses that the cancer is a solid tumor wherein the tumors comprise brain cancer, head and neck cancer, prostate cancer, liver cancer, colon cancer, lung cancer, breast
cancer, melanoma, etc. (p5, lines 3-9; claim 26,27) or metastatic cancer (p27, lines 5-9).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the primary solid tumor of NCT02820454 (6/28/2016) comprises those of liver cancer, colon cancer, lung cancer, breast cancer, melanoma, etc. as Berbeco et al. teaches of the treatment of solid tumors with the nanoparticles, such as of liver cancer, colon cancer, lung cancer, breast cancer, melanoma and also metastases, not excluding metastases caused by colon cancer, lung cancer, breast cancer, melanoma, etc.
Products of identical chemical composition can not have mutually exclusive properties. A chemical composition and its properties are inseparable. Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable and does not render the old composition patentably new to the discoverer. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
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 21,25,27-36 and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,3 and 9-13 of U.S. Patent No. 11,497,818B2 in view of NCT02820454
(6/28/2016) and Berbeco et al. (WO2018/107057A1).
The nanoparticles of U.S. Patent No. 11,497,818B2 comprise a polyorganosiloxane matrix, Gd and a chelating moiety wherein the polyorganosiloxane matrix is functionalized with the chelating moiety that encompass the gadolinium-chelated polysiloxane nanoparticles of the instant claims.
The nanoparticles of U.S. Patent No. 11,497,818B2 have a diameter from 1 to 5 nm that encompasses the hydrodynamic diameter of between 2 and 6 nm of the instant claims.
U.S. Patent No. 11,497,818B2 does not disclose the method of treating a brain metastases or imaging via MRI.
NCT02820454 (6/28/2016) discloses that stated above.
It would have been obvious to one of ordinary skill in the art to utilize the nanoparticles of U.S. Patent No. 11,497,818B2 for the method of treating a brain metastases form a primary solid tumor as NCT02820454 (6/28/2016) teaches that the AGuIX nanoparticles in doses of 15 mg/kg, 30 mg/kg, 50 mg/kg, 75 mg/kg and 100 mg/kg are advantageously used for treating brain metastases in combination with whole brain radiation therapy and imaging via MRI for the advantage of visualizing the distribution of AGuIX in brain metastases and surrounding healthy tissue
It would have been obvious to vary and/or optimize the AGuIX nanoparticle injectable solution concentration to provide the therapeutically effective doses for administration, according to the guidance provided by NCT02820454 (6/28/2016), to provide a composition having the desired concentration of therapeutically effective injected doses to determine the dose limiting toxicities and maximum tolerated dose that advantageously yields the greatest radioenhancing effect at the site of the tumor. It is noted that “[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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
The composition of U.S. Patent No. 11,497,818B2 has the same properties and is capable of the
same functions, such as being used for the method of treating a brain metastases.
U.S. Patent No. 11,497,818B2 does not disclose the method steps of injecting a first, second and third therapeutically effective amount prior to irradiation.
Berbeco et al. (WO2018/107057A1) discloses that stated above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer multiple injections of the AGuIX nanoparticles as Berbeco et al. teaches multiple administrations of the nanoparticles prior to irradiation and to allow a sufficient amount of time to allow the nanoparticles to accumulate in a cell or tissue prior to irradiation for the greatest accumulation of the radiosensitizer in the tumor cells or tissue prior to irradiation.
Conclusion
No claims are allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA JEAN PERREIRA whose telephone number is (571)272-1354. The examiner can normally be reached M9-3, T9-3, W9-3, Th9-2, F9-2.
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/MELISSA J PERREIRA/ Examiner, Art Unit 1618
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