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 Objections/Rejections Status
Claims 22-50 are pending in the application. Claims 35-50 are withdrawn from consideration.
Any objections and/or rejections from previous office actions that have not been reiterated in this office action are obviated.
The Terminal Disclaimer filed 2/19/26 was approved on 2/19/26.
New Grounds of Rejection
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.
Claim(s) 22-34 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Strosberg et al. (N. Engl. J. Med. 2017; 376: 125-135 and Protocol N°
AAA-III-01) in view of Mathur et al. (Cancer Biother. Radiopharm. 2017, 32, 266-273).
Strosberg et al. (N. Engl. J. Med. 2017; 376: 125-135 and Protocol) teaches of a pharmaceutical aqueous solution of 7.4 GBq 177Lu-DOTATATE (abstract; Protocol N° AAA-III-01: [version 11/14/11 p4, treatment; p7, Duration of treatment; p25, 1.33; p41, 5.1.1; Table 3]; [version 6/5/14 p5, treatment; p11, Duration of treatment; p30, 1.3.3; p49, 5.1.1; Table 3]; [version 11/28/14 p18, 2.4.2]; [version 6/29/15, p20, 3.4.2]) that anticipates the pharmaceutical aqueous solution of 7.4 GBq 177Lu-DOTATATE of the instant claims.
The 7.4 GBq 177Lu-DOTATATE is manufactured and supplied in monodose vials (Protocol N° AAA-III-01: [version 11/14/11, p41, 5.1.1.; p160, Instructions for the use of Lutathera 7400 MBq]; [version 6/5/14, p49, 5.1.1; p191, Instructions for the use of Lutathera 7400 MBq]; [version 11/28/14, p18, 2.4.2]; [version 6/29/15, p20, 3.4.2]) that anticipate the ready-to-use single dose of the instant claims 23 and 31.
The pharmaceutical aqueous solution is provided in a formulation solution of 22 to 25 mL (Protocol N° AAA-III-01: [version 11/14/11 p41, 5.1.1.; Table 3; p159, Nature and Contents of Container]; [version 6/5/14, p49, 5.1.1; Table 3; p189, Nature and Contents of Container]; [version 11/28/14, p18, 2.4.2]; [version 6/29/15, p20, 3.4.2]) that anticipates the volume of 20.5 to 25 mL of the instant claim 25.
The pharmaceutical aqueous solution comprises a radioconcentration of 370 MBq/mL at end of production (Protocol N° AAA-III-01: [version 11/14/11 Table 3; p158, Qualitative and Quantitative Composition]; [6/5/14 Table 3; p188, Qualitative and Quantitative Composition]) that anticipates the volumetric radioactivity of 250 to 500 MBq/mL of the instant claims.
The pharmaceutical aqueous solution comprises 0.63 mg/mL of gentisic acid and 2.8 mg/mL of
ascorbic acid for a total of 3.43 mg/mL of stabilizers (Protocol N° AAA-III-01: [version 11/14/11 Table 3]; [version 6/4/14 Table 3]) that anticipates the gentisic acid and ascorbic acid stabilizers in a total
concentration of 0.7 to 15 mg/mL of the instant claims 22 and 26.
The pharmaceutical aqueous solution comprises 0.05 mg/mL of DTPA (Protocol N° AAA-III-01: [version 11/14/11 Table 3]; [version 6/4/14 Table 3]) that anticipates the DTPA sequestering agent in a concentration of about 0.01 mg/mL to about 0.10 mg/mL of the instant claims 28-30.
The pharmaceutical aqueous solution is provided in a 30 mL vial that is closed by a rubber stopper and sealed by an aluminum cap. The vial is inserted into a lead shield container protected by a plastic sealed container (Protocol N° AAA-III-01: [version 11/14/11 p159, Nature and contents of container]; [version 6/5/14 p189, Nature and contents of container]) that anticipates the unit dose container of the instant claim 31, the lead container of the instant claim 32 and stoppered vial of the instant claim 33.
The pharmaceutical aqueous solution is administered in four equally divided doses (abstract; Protocol N° AAA-III-01: [version 11/14/11 p7, treatment; p7, Duration of treatment; p25, 1.33]; [version 6/5/14 p11, Dosage; p11, Duration of treatment]) that anticipates the pharmaceutical aqueous solution is provided in numerous dose units of the instant claim 24.
The pharmaceutical aqueous solution does not comprise any ethanol (Protocol N° AAA-III-01: [version 11/14/11 p158, Pharmaceutical Components]; [version 6/5/14 p188, Pharmaceutical Components]) and therefore, anticipates less than about 2% ethanol and less than 2% ethanol of the instant claims 22 and 34.
The pharmaceutical aqueous solution has a radiochemical purity of ≥97% and a shelf life of 72 hours at a temperature below 25°C Protocol N° AAA-III-01: ([version 11/14/11 p42, Table 3; p162, Lutathera storage requirements]; [version 6/4/14 p50, Table 3]).
The 7.4 GBq 177Lu-DOTATATE pharmaceutical aqueous solution of Strosberg et al. comprises
analogous composition components in analogous concentrations that yields an analogous volumetric radioactivity to that of the instant claims. Therefore, the 7.4 GBq 177Lu-DOTATATE pharmaceutical aqueous solution of Strosberg et al. has the same properties and is capable of the same functions, such
as a radiochemical purity as determined by HPLC of ≥95% for at least 72 hours when stored at 25°C.
Mathur et al. (Cancer Biother. Radiopharm. 2017, 32, 266-273) discloses a bulk scale “ready-to-use” 9.25 GBq 177Lu-DOTA-TATE formulation that is safe for human use for more than 1 week (radiochemical purity [Symbol font/0x3E]98%) (abstract).
The protocol for synthesis of a single patient dose comprises direct heating of 177LuCl3 with DOTA-TATE solution (0.25 mL) in ammonium acetate buffer (2.2 mL) containing gentisic acid (33 mg) (p267, Synthesis).
The reaction mixture was loaded onto a Sep-Pak® C18 cartridge to remove unreacted free 177Lu
and the column washed with 0.6 mL ethanol (p267, Synthesis).
The 177Lu-DOTA-TATE product was diluted with acetate buffer containing gentisic acid (1.5% w/v) to final radioactive concentration of 740 MBq/mL (ethanol content <10%)(abstract; p267, Synthesis).
The radiochemical purity was [Symbol font/0x3E]97.0 ± 0.5% 3 days post formulation at room temperature (Table 3) that encompasses the radiochemical purity of ≥ 95% for at least 72 h when stored at 25[Symbol font/0xB0]C of the instant claims.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the 7.4 GBq 177Lu-DOTATATE pharmaceutical aqueous solution of Strosberg et al. comprises a radiochemical purity of ≥ 95% for at least 72 h when stored at 25[Symbol font/0xB0]C as Strosberg et al. teaches that the pharmaceutical aqueous solution has a radiochemical purity of ≥97% and a shelf life of 72 hours at a temperature below 25°C but does not indicate that the temperature has to be significantly lower than 25°C and any chemist could logically assume a minor modification to radiochemical purity of ≥97% might be obtained by experimentally varying the conditions of temperature, such as a slight increase in temperature to 25°C as taught by Mathur et al.
The 370 MBq/mL 177Lu-DOTA-TATE pharmaceutical aqueous solution of Strosberg et al.
comprises a lower concentration of stabilizers and no ethanol than that of the 740 MBq/mL 177Lu-DOTA-TATE comprising a higher concentration of stabilizers and ethanol of Mathur et al. and therefore, it would have been predictable to vary and/or optimize the amount of stabilizers provided in the composition to maintain the high radiochemical purity of [Symbol font/0x3E]97.0 ± 0.5% 3 days for storage and transportation and provide a composition having the desired radiochemical purity. 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).
Response to Arguments
Applicant's arguments filed 2/24/26 have been fully considered but they are not persuasive.
Applicant asserts that Mathur et al. does not explicitly disclose less than 5% ethanol in the pharmaceutical aqueous solution wherein the lowest ethanol concentration is 6.67% v/v (or approximately 5.34% w/w) and the highest ethanol concentrations are 10% v/v (approximately 8.07% w/w) or 8% v/v (approximately 6.43% w/w).
The reference of Mathur et al. was not used to teach of the ethanol concentration but was used to teach that 740 MBq/mL 177Lu-DOTA-TATE has a radiochemical purity of [Symbol font/0x3E]97.0 ± 0.5% 3 days post formulation at room temperature as well as that stated above.
The 370 MBq/mL 177Lu-DOTA-TATE pharmaceutical aqueous solution of Strosberg et al. comprises a lower concentration of stabilizers and no ethanol than that of the 740 MBq/mL 177Lu-DOTA-TATE comprising a higher concentration of stabilizers and ethanol and therefore, it would have been predictable to vary and/or optimize the amount of stabilizers provided in the composition to maintain the high radiochemical purity of [Symbol font/0x3E]97.0 ± 0.5% 3 days for storage and transportation and provide a composition having the desired radiochemical purity. 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).
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