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 Claims 35-50 are withdrawn from consideration.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.
Applicant’s arguments, see REMARKS, filed 6/30/26, with respect to the rejection(s) of claim(s) 22-34 under 35 U.S.C. 102 and 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Maus et al. (Int. J. Diagnost. Imaging, 2014, Vol. 1, No.1 p5-12) and Chen et al. (US 2007/0269375A1).
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) 22-34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Maus et al. (Int. J. Diagnost. Imaging, 2014, Vol. 1, No.1 p5-12) in view of Chen et al. (US 2007/0269375A1).
Maus et al. (Int. J. Diagnost. Imaging, 2014, Vol. 1, No.1 p5-12) discloses 7.4 GBq 177Lu-DOTA-TATE wherein the peptide is subject to radiolysis (abstract; Introduction, especially p6, first paragraph).
The 7.4 GBq 177Lu-DOTA-TATE encompasses the 7.4 GBq 177Lu-DOTA-TATE of the instant claims.
The 177Lu-DOTA-TATE composition comprises ascorbic acid (AA) and/or gentisic acid (GA) as the addition of GA and AA quenchers was examined during and after (manual and cassette-based automated) radiolabeling of 177Lu-DOTA-TATE (1 Introduction, see p6, second paragraph; 2.2 Manual radiolabeling procedure).
The GA and AA encompass the gentisic acid and ascorbic acid of the instant claims.
The 7.4 GBq per PRRT administration and is a single patient dose (p5, 1 Introduction; 3. Studies on RCP of 177Lu-DOTA-TATE) encompasses the single dose of the instant claim 23.
A 0.25mL DTPA-solution (4 mg/mL) is added to the 177Lu-DOTA-TATE composition to complex any non-incorporated 177Lu (2.2 Manual radiolabeling procedure).
The DTPA-solution encompasses the DTPA sequestering agent of the instant claims 28 and 29.
RCP of 177Lu-DOTA-TATE without tC18 purification was ≥ 95% at 72h post radiolabeling (5.2 Radiolabeling without tC18 purification).
The degree of radiolysis of the peptide is influenced by several factors like the amount of DOTA-TATE, temperature, time, total activity, the volumic activity, quencher(s), relative amount of quencher(s), etc. (p6, first paragraph; 6 Discussion).
The manual synthesis of 177Lu-DOTA-TATE pharmaceutical aqueous solution does not include
ethanol and therefore, encompasses less than about 2% ethanol or less than 2% ethanol of the instant claims.
Maus et al. does not explicitly disclose 0.7 to 15 mg/mL of gentisic or ascorbic acid.
Maus et al. further discloses the re-addition of AA or GA after tC18 purification is 100 mmol/L (Table 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the re-addition of the quenchers GA and/or AA (100 mmol/L [Symbol font/0x7E] 15.4 mg/mL) is analogous to the initial addition of GA and/or AA and therefore, it would have been predictable to one of ordinary skill in the art that the initial additions of GA and/or AA in the manual synthesis procedure is 100 mmol/L [Symbol font/0x7E] 15.4 mg/mL with a reasonable expectation of success.
Furthermore, it is obvious to vary and/or optimize the amount of quenches GA or AA provided in the composition, according to the guidance provided by Maus, to provide a composition having the desired properties such as the desired radiolytic protection depending on the quencher(s) used and relative amount of quencher(s) added to the pharmaceutical aqueous solution. 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).
Maus et al. does not explicitly disclose a volume of 20.5 to 25 mL or a volumetric radioactivity of 250 to 500 MBq/mL.
Maus et al. further discloses that the 177Lu-DOTA-TATE composition was contained in a vial and
was diluted to a final volume of 20 mL (2.2 Manual radiolabeling procedure).
The vial encompasses the dose unit container of the instant claim 31.
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention to dilute the 177Lu-DOTA-TATE composition with saline solution to yield an injectable pharmaceutical aqueous solution having a desired volume, not excluding 20.5 to 25 mL for numerous dose units and a desired volumetric radioactivity, such as 370 MBq/mL (7.4 MBq diluted to 20 mL = 370 MBq/mL) that encompasses the 250 to 500 MBq/mL of the instant claims with a reasonable expectation.
Furthermore, it is obvious to vary and/or optimize the amount of saline solution provided in the pharmaceutical aqueous solution, according to the guidance provided by Maus, to provide a composition having the desired properties such as the desired volume of the pharmaceutical aqueous solution for the desired volumetric radioactivity. 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).
Maus et al. does not explicitly disclose about 0.01 mg/mL to about 0.10 mg/mL of DTPA.
It would have been obvious to one ordinarily skilled in the art before the effective filing date of the claimed invention to provide DTPA in a concentration, not excluding from 0.01 to 0.10 mg/mL as to rapidly capture any non-incorporated 177Lu depending on the concentrations of 177Lu and DOTA-TATE in the resulting pharmaceutical aqueous solution as Maus et al. teaches of DTPA-solution to complex any non-incorporated 177Lu and therefore, DTPA is added in a sufficient amount to completely capture any non-incorporated 177Lu.
Furthermore, it is obvious to vary and/or optimize the amount of DTPA provided in the composition, according to the guidance provided by Maus, to provide a composition having the desired properties such as the capture of non-incorporated 177Lu in the pharmaceutical aqueous solution. 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).
Maus et al. does not disclose a lead container or stoppered vial.
Chen et al. (US 2007/0269375A1) discloses stabilized radiopharmaceutical formulations
comprising stabilizers to improve the radiostability of the formulations by protecting against radiolytic damage (abstract; p1, [0026]; p2, [0018-0021]; p3, [0035]). The formulations comprises a metal radionuclide (177Lu), a metal chelator (DOTA), and the stabilizers gentisic acid, ascorbic acid, etc. (p3, [0026]; p4, [0048],[0051]; p5, [0052]; p6, [0058]).
The metal chelator (DOTA) may be linked to a targeting molecule (e.g. peptide, etc.) (p8, [0117]). The peptide comprises somatostatin (e.g. octreotide), etc. (p9, [0120]).
Stabilized radiopharmaceutical formulations are stored in sealed individual lead-shielded vials (examples 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 store the 177Lu-DOTA-TATE of Maus et al. in sealed individual lead-shielded vials to reduce exposure to the 177Lu, as Chen et al. teaches of storing stabilized 177Lu-DOTA-somatostatin radiopharmaceutical formulations in sealed lead-shielded vials.
The manually synthesized 177Lu-DOTA-TATE pharmaceutical aqueous solution of Maus et al. comprising AA or GA encompasses the 177Lu-DOTA-TATE pharmaceutical aqueous solution comprising AA or GA of the instant claims, has the same properties and is capable of the same functions, such as an RCP of ≥ 95% for at least 72 hours when stored at 25°C as determined by HPLC.
Also, 2144.04 Legal Precedent as Source of Supporting Rationale [R-07.2022]
VII. PURIFYING AN OLD PRODUCT
In re Bergstrom, 427 F.2d 1394, 166 USPQ 256 (CCPA 1970). Purer forms of known products may be
patentable, but the mere purity of a product, by itself, does not render the product nonobvious.
Conclusion
No claims are allowed at this time.
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/MELISSA J PERREIRA/Examiner, Art Unit 1618
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