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 .
Bauman Priority
This application has been filed under 35 USC 111 as a utility application as a continuation of reissue application No. 17/179,720, which is a reissue of U.S. patent No. US 10,206,875. The application was filed without any indicia that it was intended to be a reissue application itself. As a Bauman-type continuation of a reissue application, Applicant is notified that the original patent is available as prior art under 35 USC 102(a)(1) outside the grace period, and the effective filing date of the instant application does not extend beyond the actual filing date of the reissue application. See In re Bauman, 683 F.2d 405, 214 USPQ 585 (CCPA 1982).
Status of Claims
The 2/27/26 claim listing cancels claim 11 and amends claims 28, 75, and 83. Claims 1-10 and 12-109 are pending and under consideration.
The rejections under 35 U.S.C. 112 have been overcome by amendment.
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.
Claims 1-10 and 12-109 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 10,206,875.
Claims 1-10 and 12-53 are identical to the claims 1-10 and 12-53 of the ’875 Patent.
The composition of claims 54-68 are similar to the composition of the issued claims 1-16 in the ’875 Patent and further the release profile in the “wherein clause” of claim 54 is recited in claim 16 and “aqueous and oil/liquid phase” is recited in col. 16:36-41 of the ’875 patent.
Claims 69-86 reciting the method of treating cancer are similar to the method claims 17-35 and in col.11:24-29 of the ’875 patent.
Claims 87-91 reciting the method of reducing stemness are similar to the method claims 17-35 and in col.11:24-29, col.13:25 of the ’875 patent.
The specification in col.18:1-8, col.10:1-8, Example 3 and original claims in the ’875 patent include the composition of claims 92-99.
Fig.21 shows the release of the taxoid conjugate over 5, 10 and 48 hours as recited in claims 100-102.
Fig.19A shows the concentration of the conjugate over 2, 3 and 6 months as recited in claims 103-105.
The pharmaceutical composition of claims 106-108 is same as the pharmaceutical composition recited in claim 12 of the ’875 patent.
The treated cancer being resistant to 5-FU, oxaliplatin, irinotecan, docetaxel and cabazitaxel is recited in col.1:44 and col.5:50-53.
Accordingly, claims 1-10 and 12-109 are anticipated by the issued claims 1-53 and the disclosure of US 10,206,875.
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 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.
Claims 1-10, 12, 17-22, 29, 31, 36, 37, 43, 45, 54-65, 69, 71-73, 76, 78, 81, 82, 84, 86, 91-99, 106-109 remain rejected under 35 U.S.C. 103 as being unpatentable over US Patent 7,820,839 (Ojima) and US 2007/0148194 (Amiji).
Composition claims
Ojima discloses conjugates of taxoids and omega-3 fatty acids (PUFA) and pharmaceutical compositions thereof (abstract, col. 3:29-31, col.4:63-66, Examples and claims).
The claims in Ojima are drawn to several taxoid-omega-3 fatty acid (DHA, EPA, LNA) conjugates such as DHA-SBT-1214.
Ojima does not teach that the omega-3 fatty acid-taxoid conjugate is encapsulated in an oil-in-water nanoemulsion (NE) drug delivery system. However, before the claims’ effective filing date, methods of encapsulating therapeutic hydrophobic drugs in an oil-in-water nanoemulsion (NE) delivery systems were known in the art.
Amiji discloses novel NE systems comprising omega fatty acids (abstract, 0006, Fig.6). Amiji in Example 1 shows a nanoemulsion formulation of paclitaxel (0034) improved the oral delivery of the drug (0036). Amiji teaches that the pharmocokinetic studies showed that encapsulation of paclitaxel in nanoemulsions according to the invention enhanced the oral bioavailability of paclitaxel significantly (0052). Amiji shows the drug loaded nanoemulsions compared to the plain nanoemulsions (control) resulted in increased cell death (0108). Amiji further teaches that in addition to the drug delivery capabilities, the NE system can also include image contrast agents to localize and visualize the physiological effects of the drug (Example III).
Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to combine the teachings of Ojima with the teachings of Amiji in order to include a conjugate comprising a taxoid and DHA, EPA or LNA (omega-3 fatty acid) and formulate the conjugate in an oil-in-water nanoemulsion (NE) drug delivery system. A person skilled in the art would have been motivated to encapsulate the PUFA-taxoid conjugate in an oil-in-water nanoemulsion drug delivery system since Amiji showed that the NE encapsulated paclitaxel enhances the bioavailability of the drug and improve the delivery of the drug and also protection of the drug from chemical as well as enzymatic degradation (0052, 0006). One of ordinary skill in the art would have had a reasonable expectation of success to encapsulate the PUFA-taxoid conjugate in the oil-in-water nanoemulsion since Amiji showed that the NE encapsulated paclitaxel (a taxoid as in the present claim 4) has increased bioavailability. Thus, the composition of claim 1 is obvious in view of the combined teachings of Ojima and Amiji.
The composition of claim 54 is similar to claim 1. Claim 54 additionally recites that “the taxoid-conjugate is released from the NE delivery system in a formulation more slowly than the taxoid-conjugate is released from the formulation lacking the NE delivery system.” The combined teachings of Ojima and Amiji teach the composition of a PUFA-taxoid conjugate in a nanoemulsion (NE) drug delivery system. Regarding the recitation of that the NE drug delivery system comprises an aqueous phase and oil/lipid phase in claim 54, Amiji teaches novel NE delivery systems including emulsifier and aqueous phase (0007, 0023-0025). The NE delivery system can be formulated in aqueous and oil/lipid phase (0028-0029). Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to include the DHA-SBT-1214 encapsulated in NE in an aqueous phase and an oil/lipid phase to obtain a pharmaceutically active composition. The combined teachings of Ojima and Amiji teach PUFA-taxoid encapsulated in NE drug delivery system similar to the present claims, therefore the prior art composition would have the same functional property as claimed – “the taxoid-conjugate released from NE delivery system in a formulation more slowly than the taxoid-conjugate is released from the formulation lacking NE delivery system.”
Regarding claims 2 and 55’s recitation of PUFA, Ojima discloses conjugates comprising DHA-taxoid, EPA-taxoid or LNA-taxoid (col.4: 63-66, and claims 18-19).
Regarding claims 3 and 55-59’s recitation of DHA-SBT-1214, Ojima discloses DHA-SBT-1214 conjugate (Example 3 in col. 11, and claims).
Regarding the taxoids listed in claim 4, Ojima discloses several of the listed taxoids and further Amiji teaches paclitaxel. Ojima teaches that the taxoids include ortataxel, SB-T-1103, SB-T-11033, SB-T-1104, SB-T-11043, SB-T-1107, SB-T-11073, SB-T-1213, SB-T-121303, SB-T-1214, SB-T-121403, SB-T-1216, SB-T-121603, SB-T-1217, SB-T-121703, SB-T-12821, and SB-T-128221-3 (col.3:62-col.4:44 and examples). Examples of omega-3 fatty acids (PUFA) include DHA, EPA and LNA (col.4:63-66).
Regarding the PUFA-taxoid in claims 5 and 57, Ojima discloses several of the listed PUFA-taxoid conjugates (claims and examples). Examples 1-9 show DHA-taxoids, and examples 10-12 show LNA-taxoid conjugates including LNA-SB-T-1213, LNA-SBT-12303 and LNA-SBT-1103 (examples 10-12).
Regarding the requirement that the PUFA-taxoid is a DHA or LNA ester in claim 6, Ojima teaches that the PUFA (fatty acids) are coupled to the 2’-OH moiety on the taxoid via an esterification bond with the carboxylic acid moiety of the PUFA.
Regarding the NE droplet diameter ranging from 50 to 1000 nm in claims 7 and 60 and less than 200 nm in claims 8 and 61, Amiji teaches that the NE had particle size 90 nm to 119 nm (0047). This range overlaps and therefore renders the claimed range prima facie obvious.
Regarding the listed omega-3 fatty acid rich oils in claims 9, 62, and 94-96, Amiji discloses that the preferred oil in the NE delivery system includes PUFA rich oils primrose, black currant, pine nut, borage or fungal oils (0020-0021).
Regarding the recitation of “modified with a substance” in claims 10 and 63 and the “further comprising modifier” in claims 97-99, Amiji teaches that the NE delivery system further comprise surfactants, stabilizers (0026), and image contrast agents and targeting agents (0027 and Example III). Ojima teaches that the taxoid-PUFA conjugate composition can include a stabilizer, surfactant, buffering agent and/or salt (col.9: 33-36).
Regarding the surfactant is polysorbate 80 in claim 64, Ojima teaches that the taxoid-PUFA conjugate includes stabilizers such as Tween 80 (col.9:45-46).
Regarding the pharmaceutical composition comprising pharmaceutically acceptable carriers in claims 12 and 65, Ojima teaches pharmaceutical compositions comprising the PUFA-taxoid conjugates in a suitable pharmaceutical carrier (col.9:27-32), and Amiji also teaches that the NE encapsulated taxoid is combined with a pharmaceutically acceptable carrier for administration (0031-0032).
Regarding the aqueous phase comprises egg-phosphatidylcholine (E-80) or water in claims 92-93, Amiji discloses egg phosphatidylcholine (Lipoid® E80) (0048, FIG.1) or water (0025) as the emulsifier in an NE delivery system.
Regarding the pharmaceutical compositions in claims 106-108, Ojima teaches pharmaceutical compositions comprising the PUFA-taxoid conjugates in a suitable pharmaceutical carrier (col.9:27-32), and Amiji also teaches that the NE encapsulated taxoid is combined with a pharmaceutically acceptable carrier for administration (0031-0032).
Method claims
Independent Claim 17 recites a method of treating a cancer by administering an effective amount of a pharmaceutical composition comprising the PUFA-taxoid conjugate encapsulated in NE delivery system.
Claim 69 recites a method of treating cancer by administering a therapeutic amount of the composition of claim 54.
The teachings of Ojima and Amiji are as discussed above. In addition, Ojima teaches administering an effective amount of the second generation taxoid-PUFA conjugate in a pharmaceutical composition to a human patient to treat pancreatic, colon, lung and prostate cancer (col.7:60-col.9:33, claims 41-71).
Ojima does not teach that the omega-3 fatty acid-taxoid conjugate is encapsulated in an oil-in-water nanoemulsion (NE) drug delivery system. However, before the claims’ effective filing date methods of encapsulating therapeutic hydrophobic drugs in an oil-in-water nanoemulsion (NE) delivery systems were known in the art.
Amiji discloses novel NE systems comprising omega fatty acids (abstract, 0006, Fig.6). Amiji in Example 1 shows nanoemulsion formulation of paclitaxel (0034) improved the oral delivery of the drug (0036). Amiji teaches that the pharmacokinetic studies showed that encapsulation of paclitaxel in nanoemulsions according to the invention did enhance the oral bioavailability of paclitaxel significantly (0052).
Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to combine the teachings of Ojima with the teachings of Amiji in order to include a conjugate comprising a second generation taxoid and DHA, EPA or LNA (omega-3 fatty acid) and formulate the conjugate in an oil-in-water nanoemulsion (NE) drug delivery system. A person skilled in the art would have been motivated to administer the encapsulated PUFA-taxoid conjugate in a NE drug delivery system to a cancer patient since Amiji showed that the NE encapsulated paclitaxel enhances the bioavailability of the drug and improve the delivery of paclitaxel (hydrophobic drug) and also protection of the drug from chemical as well as enzymatic degradation (0052, 0006), and showed the NE delivery system has improved oral delivery of Paclitaxel. Ojima teaches administering the second generation taxoid conjugated to PUFA exhibits excellent activity against drug-resistant tumors. Thus, one of ordinary skill in the art would have had a reasonable expectation of success to treat cancer by administering the encapsulated PUFA-taxoid conjugate in oil-in-water nanoemulsion since Amiji showed that the NE encapsulated paclitaxel has increased bioavailability. Thus, claims 17 and 69 would have been obvious in view of the combined teachings of Ojima and Amiji.
Independent claim 36 recites a method of overcoming multi-drug resistance.
Ojima teaches that the second-generation taxoids exhibit excellent activity against multi-drug-resistant tumors cells (co.2:54-61) and that the disclosed improved second-generation taxoid and PUFA conjugates provide an improved method of treating a cancer in humans (col.3:1-19, Tables 1, 2, FIGS 1, 2). The second-generation taxoid-DHA conjugate (DHA-SBT-1214) exhibits antitumor effects on multi drug-resistant human colon tumor xenografts in SCID mice. Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to administer a second-generation taxoid and PUFA conjugate in NE delivery system to treat multi-drug-resistant tumors, which induces the death of the tumor cell.
Regarding claim 18’s recitation of PUFA, Ojima discloses administering conjugates comprising DHA-taxoid, EPA-taxoid or LNA-taxoid to treat cancer (col.4: 63-66, and claims 18-19).
Regarding claims 19, 37, and 71’s requirement for DHA-SBT-1214, Ojima discloses administering DHA-SBT-1214 (Example 3 in col. 11, and claims).
Regarding the taxoid listed in claims 20 and 72, Ojima discloses several of the listed taxoids and further Amiji teaches paclitaxel.
Regarding the PUFA-taxoid in claim 21, Ojima discloses several of the listed PUFA-taxoid conjugates (claims and examples). Examples 1-9 show DHA-taxoids, and examples 10-12 show LNA-taxoid conjugates including – LNA-SB-T-1213, LNA-SBT-12303 and LNA-SBT-1103 (examples 10-12).
Regarding the requirement that the PUFA-taxoid is a DHA or LNA ester in claims 22 and 73, Ojima teaches that the PUFA (fatty acids) are coupled to the 2’-OH moiety on the taxoid via an esterification bond with the carboxylic acid moiety of the PUFA.
Regarding claims 29, 43, 76, 81, 82, and 84’s requirement that the subject has paclitaxel-sensitive or paclitaxel-resistant tumors. Ojima teaches that paclitaxel and docetaxel result in multi-drug resistance (MDR) upon treatment (col.1:32-48). Ojima teaches that in contrast with paclitaxel and docetaxel, the second generation taxoid exhibits excellent activity against drug-resistant tumors cells (co.2:54-61). The disclosed improved second-generation taxoid and PUFA conjugates provide an improved method of treating a cancer in human (col.3:1-19, Tables 1, 2, FIGS 1, 2). The second-generation taxoid-DHA conjugates were evaluated for their antitumor activity against the drug-resistant human colon tumor xenograft and the drug sensitive human ovarian xenograft (Table 1). The second-generation taxoid DHA-SBT-1214 exhibits antitumor effect on drug-resistant human colon tumor xenografts in SCID mice. Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to administer a second-generation taxoid and PUFA conjugate in NE delivery system to treat paclitaxel-resistant tumors, which induces the death of the tumor cell.
Regarding the requirement that the cancer is breast, pancreatic, prostate, colon, or rectal in claims 86 and 91, Ojima teaches administering an effective amount of the second generation taxoid-PUFA conjugate in a pharmaceutical composition to a human patient to treat pancreatic, colon, lung and prostate cancer (col.7:60-col.9:33, claims 41-71).
Regarding claims 31, 45, and 78’s recitation that the method results in suppression of tumor growth, Ojima teaches that in the second-generation taxoid-DHA conjugate (DHA-SBT-1214) treated mice no trace of tumor was detected (alive on day 201) (col. 17:29-35). Amiji shows the drug loaded nanoemulsions compared to the plain nanoemulsions (control) resulted in increased cell death (0108).
Regarding the recitation “wherein the taxoid conjugate is DHA-SBT-1214” in claim 109, Ojima discloses administering DHA-SBT-1214 to treat cancer (Example 3 in col. 11, and claims).
Regarding the limitation “the cancer is resistant to 5-FU, oxaliplatin, irinotecan or cabazitaxel” in claim 109 – Ojima teaches that cancer treatment with first generation antitumor drugs paclitaxel and docetaxel results in multidrug resistance (MDR) upon treatment (col.1:15-37). Ojima teaches that the disclosed second-generation taxoid and PUFA conjugates are effective to treat the multi-drug resistant (MDR) tumors while diminishing the side effects and are tumor specific. Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to administer the DHA-SBT-1214 (PUFA conjugated second generation taxoid) in NE delivery system to treat multi-drug resistant tumors.
Claims 23-26, 30, 38-41, 44, 47, 49, 74, 77, 83, and 85 remain rejected under 35 U.S.C. 103 as being unpatentable over Ojima and Amiji as applied to claims 1 -10, 12, 17-22, 29, 31, 36, 37, 43, 45, 54-65, 69, 71-73, 76, 78, 81, 82, 84, 86, 91-99, and 106-109 above, and further in view of Botchkina (2010) (Botchkina et al. Molecular Cancer 2010, 9:192) and Botchkina (2013) (PLoS ONE. September 2012. Vol.8, Issue 9, pp. 1-16).
Independent claims 47 and 49 recite a method of eliminating a cancer stem cell (independent claim 47), and a method of reducing the stemness of a cancer stem cell (independent claim 49) by exposing the cancer stem cell to a pharmaceutical composition comprising PUFA-taxoid encapsulated in an NE delivery system.
The teachings of Ojima and Amiji are as discussed above. Ojima teaches administering an effective amount of the DHA-SBT-1214 (a second generation taxoid-PUFA conjugate) in a pharmaceutical composition to a human patient to treat pancreatic, colon, lung and prostate cancer (col.7:60-col.9:33, claims 41-71). Ojima and Amiji do not teach that the second generation taxoid-PUFA conjugate in a NE drug delivery system reduced stem-related genes in the tumorigenic cell population.
Botchkina (2010) teaches that the second generation taxoid SBT-1214 results in significant downregulation of the majority of stem-cell related genes, and leads to dramatic reduction in their sphere-forming capacity (second column in page 8 and conclusion). Botchkina (2010) teaches that the expression of several key regulators of pluripotency of embryonic stem cells, Oct-4, Sox-2, Nanog, Lin-28 and c-myc are also inhibited after single treatment with SBT-1214 for 48 hrs (page 8). Low concentrations of SBT-1214 induced downregulation of stem-related genes SOX1, RPL13Am, BMP33, NeuroG2, GJB1, GJA1, ASCL2, CTNNA1, GDF2, ALP1, S100B, CD8B1, ACTB, CCND1, FGF1, PARD6A, DVL1, GDF3, ISL1, CD3D, MME, FGFR1, RB1, BMP1, AIN1, ALDHIA1, CD8A, PPARD, FZD1, NUMB, ABCG1, ACAN, ALP1, CD8A, CDH2, COL2A1, COL9A1, DHH, DLL1, DLL3, DTX1, KRT15, MYOD, NCAM1, and NOTCH1 in CD133 positive cells (refers to claims 24-25, 38-41, 49, 74).
Botchkina (2013) teaches that the treatment with SBT-1214 downregulates genes PCNA, WT1, HOX family TFs in CD133 positive cells (refers to claims 30, 44, 77).
Since the SBT-1214 (a second-generation taxoid) downregulates multiple stem-cell related genes in CD133 positive cells, the DHA-SBT-1214 conjugate in the NE drug delivery system of Ojima in view of Amiji is also expected to provide the same effects regardless of whether it is encapsulated in a nanoemulsion.
Claims 83 and 85 recite that in addition to down regulating stemness-promoting genes, the method results in suppression of tumor growth. Ojima teaches that in the second-generation taxoid-DHA conjugate (DHA-SBT-1214) treated mice no trace of tumor was detected (alive on day 201) (col. 17:29-35). Amiji shows the drug loaded nanoemulsions compared to the plain nanoemulsions (control) resulted in increased tumor cell death (0108). Thus, a person skilled in the art before the claims’ effective filing date would have known that administering the second generation taxoid to the subject (or exposing the taxoid-PUFA conjugate to the stem cell related genes) would result in reduced expression of stemness promoting genes. Further, in view of the teachings in Ojima and Amiji, it would have been obvious to a person skilled in the art before the claims’ effective filing date that the conjugate comprising a second generation taxoid PUFA in NE drug delivery system would result in inhibiting the expression of stem cell related genes in vivo and result in increased tumor cell death.
Claims 1-10, 12-22, 28, 29, 31, 33-37, 43, 54-63, 65-73, 76, 78-82, 84, 86, 88-99, and 103-109 remain rejected under 35 U.S.C. 103 as being unpatentable over Ojima and Chen (US 2006/0067952).
Composition claims 1-10, 12-16, 54-63, 65-68, 92-99, and 103-109
The teachings of Ojima are as discussed above. Ojima discloses second generation taxoids conjugated to PUFA. Ojima does not teach PUFA-taxoid conjugate encapsulated in a nanoemulsion drug delivery system. However, before the claims’ effective filing date, injectable oil-in-water emulsions containing taxoid drugs were known in the prior art. For example, Chen discloses pharmaceutical oil-in-water emulsion compositions for delivering water insoluble taxoid drugs intravenously to treat cancer (0011, 039, 0037, Examples). The average size of the oil droplets in the emulsion is about 50 nm to 200 nm (0019, 0165), thus the emulsion is considered a nanoemulsion. The taxoid drug is docetaxel or paclitaxel (0033, 0046). Chen teaches that the taxoid emulsion composition is physically and chemically stable (0173, 0174), and the taxoid drug in the emulsion composition is stable in appropriate storage conditions for at least 6 months (0173). Chen teaches the drug-emulsion composition is 1) injectable, 2) stable under appropriate storage conditions, 3) contains a pharmaceutically effective amount of a taxoid drug, 4) contains components acceptable by regulatory agencies, 5) contains low oil content and thus does not cause hyperlipidemia, and 6) not hypoallergenic or vein irritating (0039).
Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to combine the teachings of Ojima with the teachings of Chen in order to include a conjugate comprising a second generation taxoid and DHA, EPA or LNA (omega-3 fatty acid) and formulate the conjugate in an oil-in-water nanoemulsion (NE) drug delivery system. A person skilled in the art would have been motivated to encapsulate the PUFA-taxoid conjugate in oil-in-water nanoemulsion drug delivery system since Chen teaches the drug-emulsion composition is 1) injectable, 2) stable under appropriate storage conditions, 3) contains a pharmaceutically effective amount of a taxoid drug, 4) contains components acceptable by regulatory agencies, 5) contains low oil content and thus does not cause hyperlipidemia, and 6) not hypoallergenic or vein irritating (0039). One of ordinary skill in the art would have had a reasonable expectation of success to encapsulate the PUFA-taxoid conjugate in an oil-in-water nanoemulsion since Chen showed that the NE-encapsulated paclitaxel or docetaxel (a taxoid as in the present claim 4) is injectable, stable and does not cause hyperlipidemia. Thus, the composition of claim 1 is obvious in view of the combined teachings of Ojima and Chen.
The composition of claim 54 is similar to that of claim 1. Claim 54 additionally recites that “the taxoid-conjugate is released from the NE delivery system in a formulation more slowly than the taxoid-conjugate is released from the formulation lacking the NE delivery system.” The combined teachings of Ojima and Chen teach the composition of PUFA-taxoid conjugate in a nanoemulsion (NE) drug delivery system. Chen teaches pharmaceutical oil-in-water emulsion compositions for delivering water insoluble taxoid drugs intravenously to treat cancer (0011, 039, 0037, Examples). In Chen, the emulsion includes the oil droplets of about 50 nm to 200 nm (0019, 0165), thus the emulsion is considered a nanoemulsion. Chen teaches that the injectable oil-in-water emulsion comprises a) a pharmaceutically effective amount of drug, 2) an oil component, c) a phospholipid component and d) water (an aqueous phase) (0012). Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to include the DHA-SBT-1214 conjugate encapsulated in NE drug delivery system comprising an oil-in-water emulsion. The combined teachings of Ojima and Chen teach PUFA-taxoid encapsulated in a NE drug delivery system as in the present claims, therefore the prior art composition would have the same functional property as claimed – “the taxoid-conjugate released from NE delivery system in a formulation more slowly than the taxoid-conjugate is released from the formulation lacking NE delivery system.”
Regarding claims 2-5 and 55-59 recitation of PUFA, Ojima discloses conjugates comprising DHA-taxoid, EPA-taxoid or LNA-taxoid (col.4: 63-66, and claims 18-19) specifically discloses DHA-SBT-1214 conjugate and LNA-taxoids (Examples 1-9, and claims), and Chen teaches the taxoid is docetaxel or paclitaxel.
Regarding the PUFA-taxoid is a DHA or LNA ester in claim 6, Ojima teaches that the PUFA (fatty acids) are coupled to the 2’-OH moiety on the taxoid via an esterification bond with the carboxylic acid moiety of the PUFA.
Regarding the NE droplet diameter ranging from 50 to 1000 nm in claims 7 and 60 and less than 200 nm in claims 8 and 61, Chen teaches that the average diameter of the emulsion droplet is within the range of about 50 to about 250 nm (0165).
Regarding the omega-3 fatty acid rich oil in claims 9, 62, and 94-96, Chen teaches that the oil component of the oil phase is a vegetable oil such as borage oil or black currant seed oil (0102).
Regarding the recitation of “modified with a substance” in claims 10 and 63 and “further comprising modifier” in claims 97-99, Chen teaches that the NE delivery system further contains modifiers, stabilizers (0161), compounds useful for modifying the osmolality of the emulsions (0162), and stabilizers (0170), and diagnostic agents such ultrasound contrast agents, radioactive agents, magnetic contrast agents (0052, 0095), stabilizers (claims). Ojima teaches that the taxoid-PUFA conjugate includes a stabilizer, surfactant, buffering agent and/or salt (col.9: 33-36).
Regarding the pharmaceutical composition comprising pharmaceutically acceptable carriers in claims 12 and 65, Ojima teaches pharmaceutical compositions comprising the PUFA-taxoid conjugates in a suitable pharmaceutical carrier (col.9:27-32), and Chen teaches a pharmaceutical composition comprising a NE drug delivery system for intravenous injection contains water. Thus, the pharmaceutical composition in Chen comprises a pharmaceutically acceptable carrier.
Regarding claims 13, 14, and 66’s limitation that the composition is chemically and physically stable at 4 °C for up to 6 months, Chen teaches that the nanoemulsion composition is both chemically and physically stable under appropriate storage conditions (at 2-8 °C) for about 6 months (0173, 0174, claim 17).
Regarding the functional property of the NE composition (increased retention time in the body) as in claims 15 and 67 and the requirement that the composition has release profile that is slower in the body as in claims 16 and 68, the products of identical chemical composition cannot have mutually exclusive properties. In this case, the combined teachings of Ojima and Chen teach PUFA-taxoid encapsulated in a NE drug delivery system similar to the present claims, therefore the prior art NE composition would have the same functional property as claimed.
Regarding the aqueous phase comprises egg-phosphatidylcholine (E-80) or water in claims 92-93, Chen teaches that the emulsion composition comprises egg lecithin (LIPOID® E80) and water (Examples 1, 4, Tables 1.1 and 4.1).
Regarding the NE delivery system physical stability at 4°C for up to 6 months in claims 103 and 104, Chen teaches that the nanoemulsion composition is “physically stable” under appropriate storage conditions (at 2-8 °C) for about 6 months (0174, claim 17).
Regarding the chemical stability of the taxoid in the NE delivery system in claim 105, Chen teaches that the nanoemulsion composition is both chemically and physically stable under appropriate storage conditions (at 2-8 °C) for about 6 months (0173, 0174, claim 17), and the concentration of intact taxoid drug in the composition is reduced by less than 10% under appropriate storage conditions for at least 6 months (0173).
Regarding the pharmaceutical compositions in claims 106-108, Ojima teaches pharmaceutical compositions comprising the PUFA-taxoid conjugates in a suitable pharmaceutical carrier (col.9:27-32), and Chen teaches a pharmaceutical composition comprising a NE encapsulated taxoid for injection (011, 0039, Examples 1, 4).
Method claims 17-22, 28, 29, 31, 33-37, 43, 69-73, 76, 78-82, 84, 86, 88-91, and 109
Independent Claim 17 recites a method of treating a cancer by administering an effective amount of a pharmaceutical composition comprising the PUFA-taxoid conjugate encapsulated in NE delivery system.
Claim 69 recites a method of treating cancer by administering a therapeutic amount of the composition of claim 54.
The teachings of Ojima and Chen are as discussed above. Ojima teaches administering an effective amount of the second generation taxoid-PUFA conjugate in a pharmaceutical composition to a human patient to treat pancreatic, colon, lung and prostate cancer (col.7:60-col.9:33, claims 41-71). Ojima does not teach that the omega-3 fatty acid-taxoid conjugate is encapsulated in an oil-in-water nanoemulsion (NE) drug delivery system. However, before the claims’ effective filing date, methods of encapsulating therapeutic hydrophobic drugs in an oil-in-water nanoemulsion (NE) delivery systems were known in the art. For example, see Chen.
Chen discloses pharmaceutical oil-in-water emulsion compositions for delivering water insoluble taxoid drugs intravenously to treat cancer (0011, 039, 0037, Examples). The average size of the oil droplets in the emulsion is about 50 nm to 200 nm (0019, 0165), thus the emulsion is considered a nanoemulsion. The taxoid drug is docetaxel or paclitaxel (0033, 0046). Chen teaches that the taxoid emulsion composition is physically and chemically stable (0173, 0174), and the taxoid drug in the emulsion composition is stable in appropriate storage conditions for at least 6 months (0173). Chen teaches the drug-emulsion composition is 1) injectable, 2) stable under appropriate storage conditions, 3) contains a pharmaceutically effective amount of a taxoid drug, 4) contains components acceptable by regulatory agencies, 5) contains low oil content and thus does not cause hyperlipidemia, and 6) not hypoallergenic or vein irritating (0039).
Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to combine the teachings of Ojima with the teachings of Chen in order to include a conjugate comprising a second generation taxoid and DHA, EPA or LNA (omega-3 fatty acid) and formulate the conjugate in oil-in-water nanoemulsion (NE) drug delivery system. A person skilled in the art would have been motivated to encapsulate the PUFA-taxoid conjugate in oil-in-water nanoemulsion drug delivery system since Chen teaches the drug-emulsion composition is 1) injectable, 2) stable under appropriate storage conditions, 3) contains a pharmaceutically effective amount of a taxoid drug, 4) contains components acceptable by regulatory agencies, 5) contains low oil content and thus does not cause hyperlipidemia, and 6) not hypoallergenic or vein irritating (0039). One of ordinary skill in the art would have had a reasonable expectation of success to encapsulate the PUFA-taxoid conjugate in an oil-in-water nanoemulsion since Chen showed that the NE-encapsulated paclitaxel or docetaxel (a taxoid as in the present claim 4) is injectable, stable and does not cause hyperlipidemia. Thus, claims 17 and 69 are obvious in view of the combined teachings of Ojima and Chen.
Independent claim 36 recites a method of overcoming multi-drug resistance. Ojima teaches that the second-generation taxoids exhibit excellent activity against drug-resistant tumors cells (co.2:54-61), and further teaches that the disclosed improved second-generation taxoid and PUFA conjugates provide an improved method of treating a cancer in humans (col.3:1-19, Tables 1, 2, FIGS 1, 2). The second-generation taxoid-DHA conjugate (DHA-SBT-1214) exhibits antitumor effect on drug-resistant human colon tumor xenografts in SCID mice. Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to administer a second-generation taxoid and PUFA conjugate in NE delivery system to treat paclitaxel-resistant tumors, which induces the death of the tumor cell.
Regarding claim 18’s recitation of PUFA, Ojima discloses administering conjugates comprising DHA-taxoid, EPA-taxoid or LNA-taxoid to treat cancer (col.4: 63-66, and claims 18-19).
Regarding claims 19, 37, and 71’s recitation of DHA-SBT-1214, Ojima discloses administering DHA-SBT-1214 (Example 3 in col. 11, and claims).
Regarding the taxoids listed in claims 20 and 72, Ojima discloses several of the listed taxoids, and further Chen teaches paclitaxel and docetaxel.
Regarding the PUFA-taxoid in claim 21, Ojima discloses several of the listed PUFA-taxoid conjugates (claims and examples). Examples 1-9 showed DHA-taxoids, and examples 10-12 showed LNA-taxoid conjugates including LNA-SB-T-1213, LNA-SBT-12303 and LNA-SBT-1103 (examples 10-12).
Regarding the requirement that the PUFA-taxoid is a DHA or LNA ester in claims 22 and 73, Ojima teaches that the PUFA (fatty acids) are coupled to the 2’-OH moiety on the taxoid via an esterification bond with the carboxylic acid moiety of the PUFA.
Regarding claims 29, 43, 76, 81, 82, 84’s recitation that the subject has paclitaxel-sensitive or paclitaxel-resistant tumors, Ojima teaches that paclitaxel and docetaxel result in multi-drug resistance (MDR) upon treatment (col.1:32-48). Ojima teaches that in contrast with paclitaxel and docetaxel, the second generation taxoid exhibits excellent activity against drug-resistant tumors cells (co.2:54-61). The disclosed improved second-generation taxoid and PUFA conjugates provide an improved method of treating a cancer in human (col.3:1-19, Tables 1, 2, FIGS 1, 2). The second-generation taxoid-DHA conjugates were evaluated for their antitumor activity against the drug-resistant human colon tumor xenograft and the drug sensitive human ovarian xenograft (Table 1). The second-generation taxoid DHA-SBT-1214 exhibits antitumor effect on drug-resistant human colon tumor xenografts in SCID mice. Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to administer a second-generation taxoid and PUFA conjugate in a NE delivery system to treat paclitaxel-resistant tumors, which induces the death of the tumor cell.
Regarding the requirement that the cancer is breast, pancreatic, prostate, colon, or rectal in claims 86 and 91, Ojima teaches administering an effective amount of the second generation taxoid-PUFA conjugate in a pharmaceutical composition to a human patient to treat pancreatic, colon, lung and prostate cancer (col.7:60-col.9:33, claims 41-71).
Regarding claims 31, 45, and 78’s recitation that the method results in suppression of tumor growth, Ojima teaches that in the second-generation taxoid-DHA conjugate (DHA-SBT-1214) treated mice no trace of tumor was detected (alive on day 201) (col. 17:29-35).
Regarding the recitation “wherein the taxoid conjugate is DHA-SBT-1214” in claim 109, Ojima discloses administering DHA-SBT-1214 conjugate to treat cancer (Example 3 in col. 11, and claims).
Regarding the limitation “the cancer is resistant to 5-FU, oxaliplatin, irinotecan or cabazitaxel” in claim 109, Ojima teaches that cancer treatment with first generation antitumor drugs paclitaxel and docetaxel result in multidrug resistance (MDR) upon treatment (col.1:15-37). Ojima teaches that the disclosed second-generation taxoids and PUFA conjugates are effective to treat the multi-drug resistant (MDR) tumors while diminishing the side effects and are tumor specific. Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to administer the DHA-SBT-1214 (PUFA conjugated second generation taxoid) in a NE delivery system to treat multi-drug resistant tumors.
Claims 23-26, 30, 38-41, 44, 47, 49, 74, 77, 83, and 85 remain rejected under 35 U.S.C. 103 as being unpatentable over Ojima and Chen as applied to claims 1-10, 12-22, 28, 29, 31, 33-37, 43, 54-63, 65-73, 76, 78-82, 84, 86, 88-99, and 103-109 above, and further in view of Botchkina (2010) (Molecular Cancer 2010, 9:192) and Botchkina (2013) (PLoS ONE September 2013. Vol. 8, Issue 9, pp1-16).
Independent claims 47 and 49 recite a method of eliminating a cancer stem cell (independent claim 47), and a method of reducing the stemness of a cancer stem cell (independent claim 49) by exposing the cancer stem cell to a pharmaceutical composition comprising PUFA-taxoid encapsulated in NE delivery system.
The teachings of Ojima and Chen are as discussed above. Ojima teaches administering an effective amount of DHA-SBT-1214 (second generation taxoid-PUFA conjugate) in a pharmaceutical composition to a human patient to treat pancreatic, colon, lung and prostate cancer (col.7:60-col.9:33, claims 41-71). Chen teaches a pharmaceutical composition comprising a taxoid encapsulated in a nanoemulsion. Ojima and Chen do not teach that the second generation taxoid-PUFA conjugate in NE drug delivery system reduces stem-related genes in the tumorigenic cell population.
Botchkina (2010) teaches that the second generation taxoid SBT-1214 results in significant down regulation of the majority of stem-cell related genes, and led to dramatic reduction in their sphere-forming capacity (second column in page 8 and conclusion). Botchkina teaches that the expression of several key regulators of pluripotency of embryonic stem cells, Oct-4, Sox-2, Nanog, Lin-28 and c-myc are also inhibited after single treatment with SBT-1214 for 48 hrs (page 8). Low concentrations of SBT-1214 induced down regulation of stem-related genes SOX1, RPL13Am BMP33, NeuroG2, GJB1, GJA1, ASCL2, CTNNA1, GDF2, ALP1, S100B, CD8B1, ACTB, CCND1, FGF1, PARD6A, DVL1, GDF3, ISL1, CD3D, MME, FGFR1, RB1, BMP1, AIN1, ALDHIA1, CD8A, PPARD, FZD1, NUMB, ABCG1, ACAN, ALP1, CD8A, CDH2, COL2A1, COL9A1, DHH, DLL1, DLL3, DTX1, KRT15, MYOD, NCAM1, and NOTCH1 in CD133 positive cells (refers to claims 24-25, 38-41, 49, 74).
Botchkina (2013) teaches that the treatment with SBT-1214 down regulates genes PCNA, WT1, and HOX family TFs in CD133 positive cells (refers to claims 30, 44, 77). Since the SBT-1214 (second generation of taxoid) downregulates multiple stem-cell related genes in CD133 positive cells, the DHA-SBT-1214 conjugate in NE drug delivery system is also expected to provide the same effects regardless of encapsulation in a nanoemulsion.
Claims 83 and 85 recite that in addition to downregulating stemness-promoting genes, the method results in suppression of tumor growth. Ojima teaches that in the second-generation taxoid-DHA conjugate (DHA-SBT-1214) treated mice no trace of tumor was detected (alive on day 201) (col. 17:29-35). Thus, a person skilled in the art before the claims’ effective filing date would have known that administering the second generation taxoid to the subject (or exposing the taxoid-PUFA conjugate to the stem cell related genes) would result in reduced expression of stemness promoting genes. Further, in view of the teachings in Ojima and Chen, it would have been obvious to a person skilled in the art before the claims’ effective filing date that the conjugate comprising a second generation taxoid PUFA in a NE drug delivery system would result in inhibiting the expression of stem cell related genes in vivo and result in increased tumor cell death.
Double Patenting
Statutory Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-10 and 12-53 remain rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-10 and 12-53 of prior U.S. Patent No. 10,206,875. This is a statutory double patenting rejection.
Nonstatutory 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 1-10 and 12-109 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-10, 12-17, 23-36, 38, 47, 49, and 51-90 of U.S. Patent No. RE50,096 E. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of the RE50096 E recites “a composition comprising an omega-3 polyunsaturated fatty acid (PUFA)-taxoid conjugate of DHA-SBT-1214 encapsulated in an oil-water emulsion (NE) drug delivery system, wherein the oil comprises one or more omega fatty acids and wherein said composition is formulated for parental administration.”
The reference patent’s claimed PUFA-taxoid conjugate of DHA-SBT-1214 (species) falls within the scope of the examined claim PUFA-taxoid conjugate (genus). Thus, composition claims 1-10, 12-16, 54-68, and 92-108 are anticipated by the reference ’096 composition claims 1, 9-16, 54-63, and 79-89. See MPEP 804.II.B.2.
The reference claims 17 and 64 recite “a method of treating cancer, including the steps of: administering parenterally an effective amount of a pharmaceutical composition including an omega-3 polyunsaturated fatty acid (PUFA)-taxoid conjugate of DHA-SBT-1214 encapsulated in an oil-water emulsion NE drug delivery system, wherein the oil comprises one or more omega fatty acids and wherein said composition is formulated for parental administration to a subject in need of treatment; and treating cancer chosen from the group consisting of colon, pancreatic, non-small cell lung, and prostate.” The reference method claims 17-35 recite the same method of treating cancer by administering PUFA-taxoid conjugate. Thus, claims 17-35, 69-86 and 109 are anticipated by the reference claims 17, 23-35, 64-77.
Reference claim 36 and dependent claims 38-46 recite “a method of overcoming multi-drug resistance, including the steps of: exposing a multi drug-resistant cell selected from the group consisting of colon cancer cells and prostate cancer cells to an effective amount of a pharmaceutical composition including an omega-3 polyunsaturated fatty acid (PUFA)-taxoid conjugate of DHA-SBT-1214 encapsulated in an oil-water emulsion NE drug delivery system, wherein the oil comprises one or more omega fatty acids and wherein said composition is formulated for parental administration; and inducing the death of the multi-drug resistant cell.”
The present method claims 36-46 recite the same method of overcoming multi-drug resistance by administering PUFA-taxoid conjugate. Thus, claims 36-46 are anticipated by the reference claims 36 and 38-46.
Reference Claim 47 recites a method of eliminating a cancer stem cell, and claims 49 and 78 recite a method of reducing the stemness of cancer stem cell recite exposing a cancer stem cell to a pharmaceutical composition comprising PUFA-taxoid conjugate as in the present claims 47-50, 83, 87-88. Thus, claims 47-50, 83, 87-88 are anticipated by the reference claims 47, 49, and 78.
Reference claims 51-52 recite a method of increasing retention times of an omega-3 polyunsaturated fatty acid PUFA-taxoid conjugate in the body of a subject; and claim 53 recites a method of providing a slower profile of an omega-3 polyunsaturated fatty acid PUFA-taxoid conjugate in the body of a subject as in the present claims 51-53. Thus, claims 51-53 are anticipated by the reference claims 51-53.
Claims 1-10, 12-17, 23-35, 54-86, and 92-109 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12,186,428. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of the reference ’428 recites “a pharmaceutical composition comprising an omega-3 polyunsaturated fatty acid (PUFA)-taxoid conjugate of DHA-SBT-1214 formulated in an oil-water emulsion (NE) drug delivery system in combination with an immune-oncology (10) agent of anti-PD-L1 antibody, wherein said PUFA-taxoid conjugate is NE-DHA-SBT-1214.”
The reference claim pharmaceutical composition NE-DHA-SBT-1214 (species) falls within the scope of the examined claim PUFA-taxoid conjugate (genus). Thus, the composition claims 1-16, 54-68, 92-108 are anticipated by the reference ’428 composition claims 1-5. See MPEP 804.II.B.2.
Claim 6 of the reference ’428 recites a method of treating a cancer by administering an effective amount of a pharmaceutical composition comprising NE-DHA-SBT-1214. The reference method claims 6-16 recite the same method of treating cancer by administering PUFA-taxoid conjugate as in present claims 17-35, 69-86 and 109. Thus, claims 17-35, 69-86 and 109 are anticipated by the reference claims 17, 23-35 and 64-77.
Claims 1-4, 9-10, and 17 remain rejected on the ground of nonstatutory double patenting (anticipation) as being unpatentable over claims 1, 4-9 of U.S. Patent No. 11,497,713. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 is drawn to a composition comprising an omega-3 polyunsaturated fatty acid (PUFA) -taxoid conjugate encapsulated in an oil-in-water emulsion (NE) drug delivery systems.
Claim 1 of the reference ’713 patent (by the same Applicants as the present patent) recites a method of treating a cancer by administering an effective amount of a pharmaceutical composition comprising PUFA-taxoid conjugate encapsulated in an oil-in-water nanoemulsion (NE) drug delivery system in combination with an anti-PD-L1 antibody to a subject in need thereof.
The composition of the present claim 1 is identical to the NE drug delivery system of the reference claim 1, thus reference claim 1 anticipates the present claim 1.
The composition of the present claim 2 recites that PUFA is chosen from DHA, EPA and LNA. The reference ’713 patent claim 4 recites the same PUFA, thus anticipates claim 2.
The composition of the present claim 3 recites the PUFA-taxoid conjugate is DHA-SBT-1214. The reference ’713 patent claim 5 recites the same taxoid conjugate, thus anticipates claim 3.
The composition of the present claim 4 recites the taxoid in the PUFA-taxoid and lists several known taxoids. The reference ’713 patent claim 6 recites the same taxoids as in the present claim 4 and therefore anticipates claim 4.
The composition of the present claim 9 recites that the NE is an omega-3 fatty acid rich edible oil chosen from fish oil, pine nut oil, flax-seed oil, safflower oil, primrose oil, black currant oil, borage oil, wheat germ oil, chia oil, hemp oil, perilla oil, grape oil, squalene oil and fungal oil. The reference claim 8 recites that the NE is omega-3 fatty acid rich edible oil and lists the omega-3 fatty acid rich edible oils and thus anticipates the present claim 9.
The composition of the present claim 10 recites that the oil is modified with a substance chosen from the group consisting of surfactants and targeting agents. The reference claim 9 recites that the oil is modified with surfactants and targeting agents and thus anticipates the present claim 10.
Claim 17 recites a method of treating cancer by administering a pharmaceutical composition comprising the PUFA-taxoid conjugate in NE drug delivery system comprising one or more omega fatty acids. Claim 7 of the reference depends from the method of claim 1 and recites the method of treating cancer by administering PUFA-taxoid conjugate in NE delivery system comprising omega-3 fatty acid rich edible oil. Thus, the reference claim 17 anticipates the present claim 17.
Claims 12, 54-58, 65, 69-73, 91-99 and 106-108 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5 of U.S. Patent No. 11,497,713 in view of US 2007/0148194.
The present claim 12 recites a pharmaceutical composition including a pharmaceutically acceptable carrier. The reference `713 patent claim 1 recites a pharmaceutical composition comprising a PUFA-taxoid conjugate encapsulated in a NE. The reference claim 1 does not recite the pharmaceutical composition with a pharmaceutically acceptable carrier. However, it would have been obvious to include a pharmaceutically acceptable carrier such as buffers, saline or water with the pharmaceutical compositions as shown in US 2007/0148194 (0007, 0025). Thus, claim 12 would have been obvious in view of claim 1 and US 2007/0148194.
The present claim 54 recites a composition comprising a PUFA-taxoid conjugate encapsulated in a NE drug delivery system in an aqueous phase. The reference claim 5 depends from claim 1 and recites a method of treating a cancer by administering a pharmaceutical composition comprising DHA-SBT-1214 conjugate encapsulated in NE. The reference claim 5 does not recite that the composition is in an aqueous phase as in claim 54. NE delivery system further including at least one aqueous phase was known in the art before the claims’ effective filing date. US 2007/0148194 teaches novel NE delivery systems including aqueous phase (0007, 0025). Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to include the DHA-SBT-1214 encapsulated in a NE in an aqueous phase to obtain a pharmaceutically active composition.
The present claims 55-58 recite the type of PUFA is DHA in the conjugate. The reference claim 5 recites that the PUFA-taxoid conjugate is NE-DHA-SBT-1214.
The present claim 65 depends from claim 54 and recite a pharmaceutical composition including pharmaceutically acceptable carrier. The reference claim 5 recites a pharmaceutical composition comprising NE-DHA-SBT-1214. The reference claim 5 does not recite the composition with a pharmaceutically acceptable carrier. However, it would have been obvious to include a pharmaceutically acceptable carrier such as buffer, saline or water with the pharmaceutical compositions as shown in US 2007/0148194 (0007, 0025). Thus, claim 65 would have been obvious in view of claim 5 and US 2007/0148194.
The present claims 69-73 recite a method of treating a cancer by administering to the subject a therapeutically effective amount of the composition of claim 54. The reference claim 5 recites a method of treating a cancer by administering a pharmaceutical composition comprising DHA-SBT-1214 conjugate encapsulated in a NE. US 2007/0148194 teaches novel NE delivery systems including aqueous phase (0007, 0025). Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to administer the DHA-SBT-1214 encapsulated in NE with a pharmaceutically acceptable carrier to a subject in the method of treating cancer.
The present claims 91-93 recite the aqueous phase comprises water. The reference claim 5 does not recite that the composition is in an aqueous phase as in claims 91-93. US 2007/0148194 teaches novel NE delivery systems that include water as aqueous phase (0025). Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to include the DHA-SBT-1214 encapsulated in NE in water (aqueous phase) to obtain a pharmaceutically active composition.
The present claims 94-96 recite that the oil/lipid phase comprises an omega-3 fatty acid rich oil. The reference claim 8 recites that the oil-in-water NE includes omega-3 fatty acid rich oil selected from the group consisting of primrose oil, flax-seed oil, fish oil, pine nut oil, safflower oil, black current oil, borage oil, wheat germ oil, chia oil, hemp oil, perilla oil, grape oil, squalene oil, or fungal oil. Thus, it would have been obvious to include the DHA-SBT-1214 in omega-3 fatty acid rich oil including primrose oil, flax-seed oil, fish oil, pine nut oil, safflower oil, black current oil, borage oil, wheat germ oil, chia oil, hemp oil, perilla oil, grape oil, squalene oil, or fungal oil.
The present claims 97-99 recite the NE delivery system further comprises a modifier selected from the group consisting of surfactants and targeting agents. The reference claim 9 recites that the composition includes surfactants and targeting agents as modifiers. Thus, it would have been obvious to include modifiers with the NE delivery systems.
The present claims 106-109 recite a pharmaceutical composition comprising a PUFA-taxoid conjugate encapsulated in a NE drug delivery system. The reference claim 5 depends from claim 1 and recites a method of treating a cancer by administering a pharmaceutical composition comprising DHA-SBT-1214 conjugate encapsulated in NE. US 2007/0148194 teaches novel NE delivery systems including aqueous phase (0007, 0025). Thus, it would have been obvious to a person skilled in the art before the claims’ effective filing date to include the DHA-SBT-1214 encapsulated in NE in a pharmaceutically composition.
Response to Arguments
Regarding the anticipation rejection, applicant states without explanation that “Egan, et al. does not disclose or suggest the invention as claimed.” (Reply at 1.) Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Regarding the obviousness rejections, applicant states without explanation that the cited references do not disclose or suggest the composition or methods as claimed. (Reply at 2-4.) Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Regarding the rejection under 35 U.S.C. 101 for statutory double patenting, applicant states without explanation that “the claims are not the same as” those of the ’875 patent. (Reply at 4.) Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Regarding the rejections for nonstatutory double patenting, applicant states that “these rejections can be readily overcome by the filing of a terminal disclaimer” and avers, “Applicant stands ready to provide the appropriate terminal disclaimer upon the indication of the allowance of the pending claims.” (Reply at 4.”) Until the rejections are overcome by an approved terminal disclaimer or by convincing amendment or argument, however, they must stand.
Conclusion
No claims are allowed. No claims are free of the art.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LORA E BARNHART DRISCOLL, whose telephone number is (571)272-1928. The examiner can normally be reached M-F 7:00-4:00 p.m. ET.
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/Lora E Barnhart Driscoll/Patent Reexamination Specialist, Art Unit 3991
Conferees:
/KSO/Patent Reexamination Specialist, Art Unit 3991
/Patricia L Engle/SPRS, Art Unit 3991