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 .
Status of Application
Applicant’s amendments of claim(s) 1, 5-7, 12, 16, 26, 28, and 30 in the reply filed on 08/24/2026
is acknowledged.
Claims 1-30 are under examination.
Applicant's arguments, filed 08/24/2026, have been fully considered. Rejections and/or
objections not reiterated from previous office actions are hereby withdrawn. The following rejections
and/or objections are either reiterated or newly applied. They constitute the complete set presently
being applied to the instant application.
Claim Interpretation
Claim 1 recites “in the formulated composition”. The examiner notes that the specification does not define this phrase. However, the specification does provide multiple uses such as the following, “the composition are formulated as solutions for injection …” (pg 2, para [0006], lines 1-2). Therefore, for the purposes of examination, the examiner interprets any prior art containing a solution for injection as reading on this claim phrase “in the formulated composition”.
Claim 1 recites “Fe metal content is ≤ 0.05 µg/GBq”. For the purposes of examination, the examiner interprets this to mean that the iron content, regardless of radioisotope or stable isotope, is a less than 0.05 µg per the solution radioactivity measured in GBq and any prior art containing any amount of iron near this range, or in this range, or no iron content, regardless of isotope, reads on this range limitation.
Claim 15 recites PSMA I&T content is 30-110 µg/dose. The examiner notes, in view of the specification (pg 38, para [00185], pg 40, para [00187]), this should be interpreted as the unchelated PSMA I&T content is 30-110 µg/dose.
Claim 15 additionally recites the PSMA I&T content as a µg/dose. The claims do not define the concentration denominator, “dose”. The dose is interpreted to be the amount administered to the subject. More specifically, the examiner notes that the specification regularly refers to a dose as having 200mCi (pg 75, para [00324]; pg 189, para [00662]; pg 217, para [00762]; pg 219, para [00770]) and a volume between 10 and 20 mL (pg 189, para [00662]) and that an 80 µg PSMA/dose corresponds to 0.6 µg/mCi (pg 219, para [00770]) and generally there is 2.0-3.8 ug/mL in volumes of 10-20 mL (pg 290-291, Table 62). Of particular relevance, dose is “maximum volume to be administered per dose is defined as 10 mL (200 mCi )for original formulation and 20 mL for the new formulation (200 mCi)” (pg 189, para [00662]). This creates a range for a dose to be 200mCi/10-20mL. Therefore, for the purposes of examination, the examiner interprets the range of 30 µg/dose to 110 µg/dose to be about 30-110 µg/200mCi or about 30-110 µg/10-20mL. Any prior art with a composition capable of being administered at a dose that meets this limitation, reads on Claim 15.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-10, 13-14, and 16-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weineisen, M.; et al. (Weineisen, M.; et al. 68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies. J. Nucl. Med., 2015, 56, 1169-1176; cited in the IDS filed on 4/16/2025) and McCann, J. (US 11,129,912 B1; cited in the IDS filed on 4/16/2025) as evidenced by Weineisen, M.; et al. (Weineisen, M.; et al. Synthesis and preclinical evaluation of DOTAGA-conjugated PSMA ligands for functional imaging and endoradiotherapy of prostate cancer. EJNMMI Research, 2014, 4, 63-77; cited in the IDS filed on 10/6/2025).
Weineisen, M.; et al. (hereafter referred to as Weineisen 2015) is drawn to 177Lu PSMA I&T compositions (title; abstract), and their synthesis (pg 1170, col 2, synthesis and radiolabeling), optimization (title; pg 1170, col 1, para 3, lines 14-19), and use in humans (title; abstract; pg 1170, col 1, para 3, lines 22-25).
As to claim 1, Weineisen 2015 teaches a composition comprising [177Lu]Lu-PSMA I&T (pg 1171, col 1, para 6, lines 6-8) wherein the molar ratio of PSMA I&T to 177Lu is 4.5:1.0 (pg 1171, col 2, Synthesis and Radiolabeling, para 2, lines 4-7) which falls within the claimed range of 1.0:1.0 to 8.0:1.0. In such cases, even if the prior art reference discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness. See MPEP 2144.05(I). And, Weineisen 2015 teaches that the composition may be administered to humans (pg 1173, Dosimetry of 177Lu-PSMA I&T in Mice, para 1, lines 1-3; pg 1173, Table 3; pg 1174, Figure 5).
Weineisen 2015 does not teach the pH is from 3.5-4.4.
Weineisen 2015 does not teach the Fe metal content is ≤ 0.05 µg/GBq.
Weineisen 2015 does not teach suitability of the composition for at least 72 hours after formulation.
McCann, J.; et al. (hereafter referred to as McCann) is drawn to 177Lu-PSMA I&T radiopharmaceuticals (title; abstract). McCann teaches a 177Lu-PSMA I&T radiopharmaceutical in high purity possesses extended shelf life and teaches various synthetic methods, compositions, and treatments comprising 177Lu-PSMA I&T (abstract, lines 3-5).
Regarding a pH range from 3.5-4.4, McCann teaches the composition with a pH from 4.5-7.0 (col 26, lines 52-67). This range is close to the claimed range of 3.5-4.4. In such cases, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I). Additionally, pH is a measure of the concentration of hydrogen atoms. And, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Applicant is directed to MPEP 2144.05(II)(A), "Optimization of Ranges Within Prior Art Conditions or Through Routine Experimentation", which states: “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[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.’” Therefore, as routine optimization is not considered inventive, and no evidence has been presented that the pH range was other than routine, or that the results should be considered unexpected in any way as compared to the closest prior art, the limitation is prima facie obvious.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of Weineisen 2015 to include the pH range as taught by McCann because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a composition with a pH range.
A person of ordinary skill in the art would have had a reasonable expectation of success in determining the pH range of the composition because the prior art of Weineisen 2015 disclosed a solution of the 177Lu-PSMA I&T known to be ready for injection (pg 1173, Dosimetry of 177Lu-PSMA I&T in Mice, para 1, lines 1-3; pg 1173, Table 3; pg 1174, Figure 5). Additional prior art of McCann suggested a composition of 177Lu-PSMA I&T to have similar solution properties because they are prepared the same way (col 26, lines 21-26).
The skilled artisan would have been motivated to include the pH of the solution because pH is a useful quality control metric for pharmaceutical solutions. Therefore, it would have been prima facie obvious to combine the teachings of Weineisen 2015 with McCann.
Regarding the Fe metal content is ≤ 0.05 µg/GBq, McCann teaches the composition is free of not more than 5 wt% chemical impurities (col 30, lines 18-22). This means the composition has impurities in the range of 0-5 wt% chemical impurities reads on no iron present. The claimed range of 0-0.05 µg/GBq also reads on no Fe metal present regardless of GBq amount or total weight. Therefore, the prior art range of 0-5 wt% overlaps with the ≤ 0.05 µg/GBq range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding the suitability of the composition for at least 72 hours after formulation, McCann teaches the composition can be administered to humans (col 23, lines 31-33; col 23, lines 53-62) and that the composition maintains suitability for at least 72 hours post formulation (col 22, lines 15-29).
As to claim 2, Weineisen 2015 teaches a molar ratio of PSMA I&T to 177Lu is 4.5:1.0 (pg 1171, col 2, Synthesis and Radiolabeling, para 2, lines 4-7) which falls within the claimed range of 2.0:1.0 to 8.0:1.0. In such cases, even if the prior art reference discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 3, McCann teaches a radiochemical purity of 95% or greater for at least 120 hours after formulation (col 21, lines 15-18).
As to claim 4, McCann teaches the composition can be administered in humans (col 23, lines 31-33; col 23, lines 53-62) and that the composition maintains suitability for at least 120 hours post formulation (col 22, lines 15-29).
As to claim 5, McCann teaches the composition with a pH from 4.5-7.0 (col 26, lines 52-67). The claimed range of 4.0-4.4 is close to the prior art range of 4.5-7.0. In such cases, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I). Additionally, pH is a measure of the concentration of hydrogen atoms. And, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Applicant is directed to MPEP 2144.05(II)(A), "Optimization of Ranges Within Prior Art Conditions or Through Routine Experimentation", which states: “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[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.’” Therefore, as routine optimization is not considered inventive, and no evidence has been presented that the pH range was other than routine, or that the results should be considered unexpected in any way as compared to the closest prior art, the limitation is prima facie obvious.
As to claim 6, McCann teaches the composition with a pH from 4.5-7.0 (col 26, lines 52-67). The claimed range of 4.0-4.3 is close to the prior art range of 4.5-7.0. In such cases, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I). Additionally, pH is a measure of the concentration of hydrogen atoms. And, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Applicant is directed to MPEP 2144.05(II)(A), "Optimization of Ranges Within Prior Art Conditions or Through Routine Experimentation", which states: “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[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.’” Therefore, as routine optimization is not considered inventive, and no evidence has been presented that the pH range was other than routine, or that the results should be considered unexpected in any way as compared to the closest prior art, the limitation is prima facie obvious.
As to claim 7, McCann teaches the composition with a pH from 4.5-7.0 (col 26, lines 52-67). The claimed value of 4.2 is close to the prior art range of 4.5-7.0. In such cases, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I). Additionally, pH is a measure of the concentration of hydrogen atoms. And, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. Applicant is directed to MPEP 2144.05(II)(A), "Optimization of Ranges Within Prior Art Conditions or Through Routine Experimentation", which states: “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[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.’” Therefore, as routine optimization is not considered inventive, and no evidence has been presented that the pH range was other than routine, or that the results should be considered unexpected in any way as compared to the closest prior art, the limitation is prima facie obvious.
As to claim 8, Weineisen 2015 teaches a 4.5-fold molar excess of PSMA I&T (pg 1171, col 2, synthesis and radiolabeling, para 2, lines 4-7) which falls within the claimed range of 2.0:1.0 to 7.0:1.0. In such cases, even if the prior art reference discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 9, Weineisen 2015 teaches a 4.5-fold molar excess of PSMA I&T (pg 1171, col 2, synthesis and radiolabeling, para 2, lines 4-7) which falls within the claimed range of 2.0:1.0 to 6.0:1.0. In such cases, even if the prior art reference discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 10, Weineisen 2015 teaches a 4.5-fold molar excess of PSMA I&T (pg 1171, col 2, synthesis and radiolabeling, para 2, lines 4-7) which falls within the claimed range of 2.0:1.0 to 5.0:1.0. In such cases, even if the prior art reference discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness. See MPEP 2144.05(I).
Weineisen, M.; et al. (hereafter referred to as Weineisen 2014) is drawn to synthesis and preclinical use of 177Lu-PSMA I&T-type molecules (title; abstract; pg 3, Figure 2) including methods of chelating (pg 5, col 2, para 2-8; pg 6, col 1, para 4-5; pg 6, col 2, para 2).
As to claim 11, Weineisen 2015 teaches a 4.5-fold molar excess of PSMA I&T (pg 1171, col 2, synthesis and radiolabeling, para 2, lines 4-7) which does not overlap with the claimed ranges but it is close. In such cases, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I).
Additionally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. “[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.” As evidenced by Weineisen 2014, adjusting the molar ratio of PSMA I&T to 177Lu can be successful even if the PSMA I&T to 177Lu is adjusted to 1.0:2.5 (Weineisen 2014, pg 5, col 2, para 8, line 2). Since, a range can be disclosed in multiple prior art references instead of in a single prior art, this provides evidence that a molar range from 4.5:1.0 to 1.0:2.5 is workable. See MPEP 2144.05(I). The claimed amount of 2.0:1.0 lies inside the prior art range of 4.5:1.0 to 1.0:2.5. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. Applicant is directed to MPEP 2144.05(II)(A), "Optimization of Ranges Within Prior Art Conditions or Through Routine Experimentation", which states: “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[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.’” Therefore, as routine optimization is not considered inventive, and no evidence has been presented that the concentration of PSMA I&T was other than routine, or that the results should be considered unexpected in any way as compared to the closest prior art, the limitation is prima facie obvious.
As to claim 12, Weineisen 2015 teaches a 4.5-fold molar excess of PSMA I&T (pg 1171, col 2, synthesis and radiolabeling, para 2, lines 4-7) which does not overlap with the claimed ranges but it is close. In such cases, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I).
Additionally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. “[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.” See MPEP 2144.05(II)(A). As evidenced by Weineisen 2014, adjusting the molar ratio of PSMA I&T to 177Lu can be successful even if the PSMA I&T to 177Lu is adjusted to 1.0:2.5 (Weineisen 2014, pg 5, col 2, para 8, line 2). Since, a range can be disclosed in multiple prior art references instead of in a single prior art, this provides evidence that a molar range from 4.5:1.0 to 1.0:2.5 is workable. See MPEP 2144.05(I). The claimed amount of 2.0:1.0 lies inside the prior art range of 4.5:1.0 to 1.0:2.5. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Additionally, applicant is directed to MPEP 2144.05(II)(A), "Optimization of Ranges Within Prior Art Conditions or Through Routine Experimentation", which states: “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[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.’” Therefore, as routine optimization is not considered inventive, and no evidence has been presented that the concentration of PSMA I&T was other than routine, or that the results should be considered
As to claim 13, Weineisen 2015 teaches a 4.5-fold molar excess of PSMA I&T (pg 1171, col 2, synthesis and radiolabeling, para 2, lines 4-7) which falls within the claimed range of 3.0:1.0 to 8.0:1.0. In such cases, even if the prior art reference discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 14, Weineisen 2015 teaches a 4.5-fold molar excess of PSMA I&T (pg 1171, col 2, synthesis and radiolabeling, para 2, lines 4-7) which falls within the claimed range of 3.0:1.0 to 6.0:1.0. In such cases, even if the prior art reference discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 16, McCann teaches the composition is free of not more than 5 wt% chemical impurities (col 30, lines 18-22). This means the composition has impurities in the range of 0-5 wt% chemical impurities reads on no iron present. The claimed range of Fe metal content ≤ 0.03 µg/GBq also reads on no Fe metal present regardless of GBq amount or total weight. Therefore, the prior art range of 0-5 wt% overlaps with the ≤ 0.05 µg/GBq range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
As to claim 17, McCann teaches the composition is free of not more than 5 wt% chemical impurities (col 30, lines 18-22). This means the composition has impurities in the range of 0-5 wt% chemical impurities reads on no copper metal present. The claimed range of Cu metal content ≤ 0.05 µg/GBq also reads on no Cu metal present regardless of GBq amount or total weight. Therefore, the prior art range of 0-5 wt% overlaps with the ≤ 0.05 µg/GBq range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
As to claim 18, McCann teaches the composition is free of not more than 5 wt% chemical impurities (col 30, lines 18-22). This means the composition has impurities in the range of 0-5 wt% chemical impurities reads on no Zn metal present. The claimed range of Zn metal content ≤ 0.05 µg/GBq also reads on no Zn metal present regardless of GBq amount or total weight. Therefore, the prior art range of 0-5 wt% overlaps with the ≤ 0.05 µg/GBq range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
As to claim 19, McCann teaches the composition is free of not more than 5 wt% chemical impurities (col 30, lines 18-22). This means the composition has impurities in the range of 0-5 wt% chemical impurities reads on no Pb metal present. The claimed range of Pb metal content ≤ 0.05 µg/GBq also reads on no Pb metal present regardless of GBq amount or total weight. Therefore, the prior art range of 0-5 wt% overlaps with the ≤ 0.05 µg/GBq range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
As to claim 20, McCann teaches a radiochemical purity of 97.5% or greater at 72 hours after production (col 10, lines 1-3).
As to claim 21, McCann teaches a radiochemical purity of 98.0% or greater at 72 hours after production (col 10, lines 1-3).
As to claim 22, McCann teaches the composition is suitable for human administration for 7 or more cycles of treatment (col 24, lines 25-27).
As to claim 23, McCann teaches the composition further comprises about 5-120 mg/mL ascorbic acid (col 9, lines 23-29). The claimed range of 10-50mg/mL lies fully within this range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
As to claim 24, McCann teaches the composition further comprises about 5-120 mg/mL ascorbic acid (col 9, lines 23-29). The claimed range of 10-50mg/mL lies fully within this range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
As to claim 25, McCann teaches a composition further comprising DTPA (col 23, lines 10-14).
As to claim 26, McCann teaches the composition is free of not more than 5 wt% chemical impurities (col 30, lines 18-22). This means the composition has impurities in the range of 0-5 wt% chemical impurities reads on no Cu, Zn, and Pb metal present. The claimed range of Cu metal content ≤ 0.05 µg/GBq, Zn metal content ≤ 0.05 µg/GBq, and Pb metal content ≤ 0.05 µg/GBq also reads on no 0 µg/GBq metal present, which is equivalent to 0 wt%. Therefore, the prior art range of 0-5 wt% overlaps with the ≤ 0.05 µg/GBq range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
As to claim 27, McCann teaches a radiopharmaceutical kit (col 25, lines 37-49).
As to claim 28, Weineisen 2015 teaches a composition comprising [177Lu]Lu-PSMA I&T (pg 1171, col 1, para 6, lines 6-8) wherein the molar ratio of PSMA I&T to 177Lu is 4.5:1.0 (pg 1171, col 2, Synthesis and Radiolabeling, para 2, lines 4-7) which falls within the claimed range of 2.0:1.0 to 6.0:1.0. In such cases, even if the prior art reference discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness. See MPEP 2144.05(I). And, Weineisen 2015 teaches that the composition may be administered to humans (pg 1173, Dosimetry of 177Lu-PSMA I&T in Mice, para 1, lines 1-3; pg 1173, Table 3; pg 1174, Figure 5).
Weineisen 2015 does not teach suitability of the composition for administration to a human patient for at least 72 hours after formulation.
Weineisen 2015 does not teach the radiochemical purity (RCP) of 95% or greater for at least 72 hours after formulation.
Regarding the suitability of the composition for at least 72 hours after formulation, McCann teaches the composition can be administered to humans (col 23, lines 31-33; col 23, lines 53-62) and that the composition maintains suitability for at least 72 hours post formulation (col 22, lines 15-29).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of Weineisen 2015 to include suitability for administration to human patients as taught by McCann because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a composition suitable for administration to humans in a timeframe.
A person of ordinary skill in the art would have had a reasonable expectation of success in administering a 177Lu-PSMA I&T composition to a human patient in need thereof for at least 72 hours after formulation because the prior art of Weineisen 2015 disclosed a composition known to have 177Lu and PSMA I&T useful for in vivo application (pg 1171, col 1, para 6, lines 6-8). Additional prior art of McCann suggested a similar composition of 177Lu and PSMA I&T to have similar properties because of the same synthetic methods between them involves known chemistry and formulation (McCann, col 26, lines 21-29).
The skilled artisan would have been motivated to have a composition suitable for administration to a human patient in need therefore for at least 72 hours after formulation because clinics may need to formulate more material than needed for a single patient or may want to perform quality control after formulation but before use. In both cases, longer stability of the product is advantageous. Therefore, it would have been prima facie obvious to combine the teachings of Weineisen 2015 with McCann.
Regarding radiochemical purity (RCP) of 95% or greater for at least 72 hours after formulation, McCann teaches the composition maintains suitability with a radiochemical purity of 95% or greater for at least 72 hours post formulation (col 10, lines 1-3).
As to claim 29, McCann teaches a radiochemical purity of 95% or greater for at least 120 hours after formulation (col 10, lines 1-3).
As to claim 30, Weineisen 2015 teaches a composition comprising [177Lu]Lu-PSMA I&T (pg 1171, col 1, para 6, lines 6-8) wherein the molar ratio of PSMA I&T to 177Lu is 4.5:1.0 (pg 1171, col 2, Synthesis and Radiolabeling, para 2, lines 4-7) which is close to the claimed range of 2.0:1.0 to 4.0:1.0. In such cases, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Additionally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144.05(II)(A). And, Weineisen 2015 teaches that the composition may be administered to humans (pg 1173, Dosimetry of 177Lu-PSMA I&T in Mice, para 1, lines 1-3; pg 1173, Table 3; pg 1174, Figure 5).
Weineisen 2015 does not teach the pH is from 3.5-4.4.
Weineisen 2015 does not teach the Fe metal content is ≤ 0.05 µg/GBq, Cu metal content is ≤ 0.05 µg/GBq, Zn metal content is ≤ 0.05 µg/GBq, and Pb metal content is ≤ 0.05 µg/GBq.
Weineisen 2015 does not teach suitability of the composition for at least 72 hours after formulation.
Weineisen 2015 does not teach the composition has a radiochemical purity (RCP) of 97.5% or greater for at least 72 hours after formulation.
Regarding a pH range from 3.5-4.4, McCann teaches the composition with a pH from 4.5-7.0 (col 26, lines 52-67). This range is close to the claimed range of 3.5-4.4. In such cases, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I). Additionally, pH is a measure of the concentration of hydrogen atoms. And, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05(II)(A). Applicant is directed to MPEP 2144.05(II)(A), "Optimization of Ranges Within Prior Art Conditions or Through Routine Experimentation", which states: “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[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.’” Therefore, as routine optimization is not considered inventive, and no evidence has been presented that the pH range of 3.5-4.4 was other than routine, or that the results should be considered unexpected in any way as compared to the closest prior art, the limitation is prima facie obvious.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of Weineisen 2015 to include the pH range as taught by McCann because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a composition with a pH range.
A person of ordinary skill in the art would have had a reasonable expectation of success in determining the pH range of the composition because the prior art of Weineisen 2015 disclosed a solution of the 177Lu-PSMA I&T known to be ready for injection (pg 1173, Dosimetry of 177Lu-PSMA I&T in Mice, para 1, lines 1-3; pg 1173, Table 3; pg 1174, Figure 5). Additional prior art of McCann suggested a composition of 177Lu-PSMA I&T to have similar solution properties because of they are prepared the same way (col 26, lines 21-26).
The skilled artisan would have been motivated to include the pH of the solution because pH is a useful quality control metric for pharmaceutical solutions and is helpful in determining compatibility with the subject. Therefore, it would have been prima facie obvious to combine the teachings of Weineisen 2015 with McCann.
Regarding the Fe metal content is ≤ 0.05 µg/GBq, Cu metal content is ≤ 0.05 µg/GBq, Zn metal content is ≤ 0.05 µg/GBq, and Pb metal content is ≤ 0.05 µg/GBq, McCann teaches the composition is free of not more than 5 wt% chemical impurities (col 30, lines 18-22). This means the composition has impurities in the range of 0-5 wt% chemical impurities reads on no Fe, Cu, Zn, and Pb metal present. The claimed range of Fe metal content is ≤ 0.05 µg/GBq, Cu metal content ≤ 0.05 µg/GBq, Zn metal content ≤ 0.05 µg/GBq, and Pb metal content ≤ 0.05 µg/GBq also reads on no 0 µg/GBq metal present, which is equivalent to 0 wt%. Therefore, the prior art range of 0-5 wt% overlaps with the ≤ 0.05 µg/GBq range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding the suitability of the composition for at least 72 hours after formulation, McCann teaches the composition can be administered to humans (col 23, lines 31-33; col 23, lines 53-62) and that the composition maintains suitability for at least 72 hours post formulation (col 22, lines 15-29).
Regarding the composition has a radiochemical purity (RCP) of 97.5% or greater for at least 72 hours after formulation, McCann teaches the composition maintains suitability with a radiochemical purity of at least 95% for at least 72 hours post formulation (col 10, lines 1-3). The claimed range of 97.5 or greater lies inside the prior art range of at least 95%. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weineisen 2015 and McCann as applied to claims s 1-10, 13-14, and 16-30 above, and further in view of Weineisen, M.; et al. (Weineisen, M.; et al. 68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies. Supplementary Information. J. Nucl. Med., 2015, 56, 1169-1176; cited in the IDS filed on 4/25/2025). The teachings of Weineisen 2015 and McCann and Weineisen 2014 as applied in the previous rejections are incorporated in this rejection.
As to claim 15, McCann teaches a dose for a human within the range of 1 GBq to 30 GBq (col 24, lines 1-7)
McCann does not expressly teach the amount of PSMA I&T in each dose.
Weineisen, M.; et al (hereafter referred to as Weineisen Supplementary) is drawn to the materials and methods of making the materials and tabulations of results of Weineisen 2015 (title; body of document; supplementary figure 1; supplementary table 1; supplementary table 2).
Regarding the amount of PSMA I&T in each dose, Weineisen Supplementary teaches 150-200 µg PSMA I&T for a 6-8 GBq (about 160-216 mCi) (pg 2, para 3, lines 1-2) formulation. This gives a range of 18.75-33.3 µg/GBq (0.69-1.25 µg/mCi) suitable for use in human. McCann gives a dose of 1-30 GBq (col 24, lines 1-7) which corresponds to a 18.75-999 ug/dose. The claimed range of 30-120 ug/dose PSMA I&T lies fully within this range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of the combined teachings of Weineisen 2015 and McCann to include the dose as taught by Weineisen Supplementary because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a PSMA I&T content.
A person of ordinary skill in the art would have had a reasonable expectation of success in having a composition with a PSMA I&T content of 30-110 µg/dose because the prior art of McCann disclosed doses for compositions for human patients (McCann, col 24, lines 1-7) known to be made according to a method by Weineisen 2015 (McCann, col 26, lines 21-29). Additional prior art of Weineisen Supplementary, which is the supplementary information of Weineisen 2015, suggested similar 177Lu-PSMA I&T compositions to have similar doses because of the overlap of the composition between them involves known chemistry and preparation.
The skilled artisan would have been motivated to use the PSMA I&T content of 30-110 µg/dose because the concentration needs to be at a level to cause therapeutic benefit and the prior art taught that an amount of PSMA I&T around these values could be effective for 177Lu. Therefore, it would have been prima facie obvious to combine the teachings of Weineisen 2015 and McCann with Weineisen Supplementary.
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.
Copending Application No. 18/681,264 and Copending Application No. 18/798,723
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 20 of copending Application No. 18/681,264 in view of Weineisen 2015, McCann, Weineisen 2014, and Weineisen Supplementary.
This is a provisional nonstatutory double patenting rejection.
Claims 1-30 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/798,723 in view of Weineisen 2015, McCann, Weineisen 2014, and Weineisen Supplementary.
This is a provisional nonstatutory double patenting rejection.
Instant claims require a composition of 177Lu-PSMA I&T with a molar ratio between 1.0:1.0 to 8.0:1.0 of PSMA I&T to 177Lu, suitable for use in humans, and stable for at least 72 hours and in some case stability of up to 120 hours, and a pH range between 3.5 and 4.4, and trace metal impurities of Fe, Cu, Zn, and, Pb less than or equal to 0.05 ug/GBq, ascorbic acid, and DTPA.
Conflicting claims of copending application no. 18/681,264 (hereafter referred to as ‘264) and copending application no. 18/798,723 (hereafter referred to as ‘723) teach a lanthanide metal chelated to PSMA I&T.
Conflicting claims of ‘264 and ‘723 do not teach stability with a radiochemical purity of 95-99% or higher up to 120hrs after formulation.
Conflicting claims of ‘264 and ‘723 do not teach molar ratios of 1.0:1.0 to 8.0:1.0 of PSMA I&T to 177Lu.
Conflicting claims of ‘264 and ‘723 do not teach pH ranges 3.5-4.4.
Conflicting claims of ‘264 and ‘723 do not teach trace metal impurities of Fe, Cu, Zn, and, Pb less than or equal to 0.05 ug/GBq.
Conflicting claims of ‘264 and ‘723 do not teach ascorbic acid from 10-50 mg/mL.
Conflicting claims of ‘264 and ‘723 do not teach DTPA.
McCann is drawn to 177Lu-PSMA I&T radiopharmaceuticals (title; abstract). McCann teaches a 177Lu-PSMA I&T radiopharmaceutical in high purity possesses extended shelf life and teaches various synthetic methods, compositions, and treatments comprising 177Lu-PSMA I&T (abstract, lines 3-5).
Regarding molar ratios of 1.0:1.0 to 8.0:1.0, Weineisen 2015 teaches a molar ratio of PSMA I&T to 177Lu is 4.5:1.0 (pg 1171, col 2, Synthesis and Radiolabeling, para 2, lines 4-7) which falls within the claimed range of 2.0:1.0 to 8.0:1.0. In such cases, even if the prior art reference discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness. See MPEP 2144.05(I). Additionally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05(II)(A).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of the conflicting claims of ‘264 and ‘723 to include molar ratios as taught by Weineisen 2015 because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a composition made from molar ratios of PSMA I&T and 177Lu.
A person of ordinary skill in the art would have had a reasonable expectation of success in using the molar ratios of Weinesen 2015 to make compositions similar to the conflicting claims of ‘264 and ‘723 because the prior art of conflicting claims disclosed compositions of 177Lu and PSMA I&T known to be made by complexing 177Lu with PSMA I&T. Additional prior art of Weineisen 2015 suggested specific ratios for the complexation to have similar result of a composition comprising 177Lu PSMA I&T because of the overlap of structure between them involves known chemistry.
The skilled artisan would have been motivated to use the molar ratios because it had been shown successful for the synthesis of 177Lu PSMA I&T. Therefore, it would have been prima facie obvious to combine the teachings of the conflicting claims of ‘264 and ‘723 with Weineisen 2015.
Regarding pH ranges of 3.5-4.4, McCann teaches the composition with a pH from 4.5-7.0 (col 26, lines 52-67). This range is close to the claimed range of 3.5-4.4. In such cases, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I). Additionally, pH is a measure of the concentration of hydrogen atoms. And, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05(II)(A).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of the conflicting claims of ‘264 and ‘723 and Weineisen 2015 to include the pH range as taught by McCann because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a composition with a pH range.
A person of ordinary skill in the art would have had a reasonable expectation of success in determining the pH range of the composition because the conflicting claims of ‘264 and ‘723 and the prior art of Weineisen 2015 disclosed a solution of the 177Lu-PSMA I&T known to be ready for injection (pg 1173, Dosimetry of 177Lu-PSMA I&T in Mice, para 1, lines 1-3; pg 1173, Table 3; pg 1174, Figure 5). Additional prior art of McCann suggested a composition of 177Lu-PSMA I&T to have similar solution properties because of they are prepared the same way (col 26, lines 21-26).
The skilled artisan would have been motivated to include the pH of the solution because pH is a useful quality control metric for pharmaceutical solutions and is helpful in determining compatibility with the subject. Therefore, it would have been prima facie obvious to combine the teachings of the conflicting claims of ‘264 and ‘723 and Weineisen 2015 with McCann.
Regarding stability with a radiochemical purity of 95-99% or higher up to 120hrs after formulation, McCann teaches a radiochemical purity of 99% or greater for at least 120 hours after formulation (col 10, lines 1-3).
Regarding trace metal impurities of Fe, Cu, Zn, and, Pb less than or equal to 0.05 ug/GBq, McCann teaches the composition is free of not more than 5 wt% chemical impurities (col 30, lines 18-22). This means the composition has impurities in the range of 0-5 wt% chemical impurities reads on no Fe, Cu, Zn, and Pb metal present. The claimed range of Fe metal content is ≤ 0.05 µg/GBq, Cu metal content ≤ 0.05 µg/GBq, Zn metal content ≤ 0.05 µg/GBq, and Pb metal content ≤ 0.05 µg/GBq also reads on no 0 µg/GBq metal present, which is equivalent to 0 wt%. Therefore, the prior art range of 0-5 wt% overlaps with the ≤ 0.05 µg/GBq range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding ascorbic acid from 10-50mg/mL, McCann teaches the composition further comprises about 5-120 mg/mL ascorbic acid (col 9, lines 23-29). The claimed range of 10-50mg/mL lies fully within this range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding DTPA, McCann teaches a composition further comprising DTPA (col 23, lines 10-14).
Copending Application No. 18/791,256 and Copending Application No. 18/791,270
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 15, 23-27 of copending Application No. 18/791,256 in view of Weineisen 2015 and McCann.
This is a provisional nonstatutory double patenting rejection.
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 15-18, 25-29 of copending Application No. 18/791,270 in view of Weineisen 2015 and McCann.
This is a provisional nonstatutory double patenting rejection.
Instant claims require a composition of 177Lu-PSMA I&T with a molar ratio between 1.0:1.0 to 8.0:1.0 of 177Lu to PSMA I&T, suitable for use in humans, and stable for at least 72 hours and in some case stability of up to 120 hours, and a pH range between 3.5 and 4.4, and trace metal impurities of Fe, Cu, Zn, and, Pb less than or equal to 0.05 ug/GBq, and DTPA and ascorbic acid.
Conflicting claims of copending application no. 18/791,256 (hereafter referred to as ‘256) and copending application no. 18/791,270 (hereafter referred to as ‘270) teach the composition of 177Lu-PSMA I&T. And ‘256 teaches a molar ratio of 8.0:1.0 to 11.0:1.0 and ‘270 teaches a molar ratio of 3.0:1 to 8.0:1.0. In each case, the molar ratio ranges overlap. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). And ‘256 and ‘270 teach a radiochemical purity of at least 95% for at least 72 hours post production.
The claims of ‘256 and ‘270 do not teach a pH range between 3.5 and 4.4.
The claims of ‘256 and ‘270 do not teach stability up to 120 hours.
The claims of ‘256 and ‘270 do not teach do not teach trace metal impurities of Fe, Cu, Zn, and, Pb less than or equal to 0.05 ug/GBq.
The claims of ‘256 and ‘270 do not teach ascorbic acid in a range of 10-50mg/mL.
The claims of ‘256 and ‘270 do not teach DTPA
Regarding pH ranges of 3.5-4.4, McCann teaches the composition with a pH from 4.5-7.0 (col 26, lines 52-67). This range is close to the claimed range of 3.5-4.4. In such cases, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I). Additionally, pH is a measure of the concentration of hydrogen atoms. And, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05(II)(A).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of the conflicting claims of ‘256 and ‘270 to include the pH range as taught by McCann because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a composition with a pH range.
A person of ordinary skill in the art would have had a reasonable expectation of success in determining the pH range of the composition because the conflicting claims of ‘256 and ‘270 disclosed a solution of the 177Lu-PSMA I&T known to be ready for injection. Additional prior art of McCann suggested a composition of 177Lu-PSMA I&T to have similar solution properties because of the overlap of the 177Lu and PSMA I&T.
The skilled artisan would have been motivated to include the pH of the solution because pH is a useful quality control metric for pharmaceutical solutions and is helpful in determining compatibility with the subject. Therefore, it would have been prima facie obvious to combine the teachings of the conflicting claims of ‘256 and ‘270 with McCann.
Regarding stability with a radiochemical purity of 95-99% or higher up to 120hrs after formulation, McCann teaches a radiochemical purity of 99% or greater for at least 120 hours after formulation (col 10, lines 1-3).
Regarding trace metal impurities of Fe, Cu, Zn, and, Pb less than or equal to 0.05 ug/GBq, McCann teaches the composition is free of not more than 5 wt% chemical impurities (col 30, lines 18-22). This means the composition has impurities in the range of 0-5 wt% chemical impurities reads on no Fe, Cu, Zn, and Pb metal present. The claimed range of Fe metal content is ≤ 0.05 µg/GBq, Cu metal content ≤ 0.05 µg/GBq, Zn metal content ≤ 0.05 µg/GBq, and Pb metal content ≤ 0.05 µg/GBq also reads on no 0 µg/GBq metal present, which is equivalent to 0 wt%. Therefore, the prior art range of 0-5 wt% overlaps with the ≤ 0.05 µg/GBq range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding ascorbic acid from 10-50mg/mL, McCann teaches the composition further comprises about 5-120 mg/mL ascorbic acid (col 9, lines 23-29). The claimed range of 10-50mg/mL lies fully within this range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding DTPA, McCann teaches a composition further comprising DTPA (col 23, lines 10-14).
Copending Application No. 18/228,510 and Copending Application No. 18/354,581
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 7, 35, 39, 44, and 45 of copending Application No. 18/228,510 in view of Weineisen 2015 and McCann.
This is a provisional nonstatutory double patenting rejection.
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 10-11, 13, 17-22, 28-30 of copending Application No. 18/354,581 in view of Weineisen 2015 and McCann.
This is a provisional nonstatutory double patenting rejection.
Instant claims require a composition of 177Lu-PSMA I&T with a molar ratio between 1.0:1.0 to 8.0:1.0 of PSMA I&T 177Lu, suitable for use in humans, and stable for at least 72 hours and in some case stability of up to 120 hours, and a pH range between 3.5 and 4.4, and trace metal impurities of Fe, Cu, Zn, and, Pb less than or equal to 0.05 ug/GBq, and DTPA and ascorbic acid.
Conflicting claims of copending application no. 18/228,510 (hereafter referred to as ‘510) and copending application no. 18/354,581 (hereafter referred to as ‘581) teach lanthanide PSMA I&T compositions for use in humans with pH ranges for ‘510 from 3.5-4.2 and for ‘581 from 5.5-7.5. In the case of ‘510, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05(I). In the case of ‘581, the claimed ranges "overlap or lie inside ranges disclosed by the prior art", so a prima facie case of obviousness exists. See MPEP 2144.05(I). ‘510 and ‘581 teach ascorbic acid. ‘510 teaches a radiochemical purity of at least 95% for at least 90 hours and ‘581 teaches a radiochemical purity of at least 96%.
The conflicting claims of ‘510 and ‘581 do not teach molar ratios of 1.0:1.0 to 8.0:1.0 of PSMA I&T to 177Lu.
The conflicting claims of ‘510 and ‘581 do not teach trace metal impurities.
The conflicting claims of ‘510 and ‘581 do not teach ascorbic acid.
The conflicting claims of ‘510 and ‘581 do not teach DTPA.
Regarding the molar ratios, Weineisen 2015 teaches a molar ratio of PSMA I&T to 177Lu is 4.5:1.0 (pg 1171, col 2, Synthesis and Radiolabeling, para 2, lines 4-7) which falls within the claimed range of 2.0:1.0 to 8.0:1.0. In such cases, even if the prior art reference discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness. See MPEP 2144.05(I). Additionally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05(II)(A).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of the conflicting claims of ‘510 and ‘581 to include molar ratios as taught by Weineisen 2015 because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a composition made from molar ratios of PSMA I&T and 177Lu.
A person of ordinary skill in the art would have had a reasonable expectation of success in using the molar ratios of Weineisen 2015 to make compositions similar to the conflicting claims of ‘510 and ‘581 because the prior art of conflicting claims disclosed compositions of 177Lu and PSMA I&T known to be made by complexing 177Lu with PSMA I&T. Additional prior art of Weineisen 2015 suggested specific ratios for the complexation to have similar result of a composition comprising 177Lu PSMA I&T because of the overlap of structure between them involves known chemistry.
The skilled artisan would have been motivated to use the molar ratios because it had been shown successful for the synthesis of 177Lu PSMA I&T. Therefore, it would have been prima facie obvious to combine the teachings of the conflicting claims of ‘510 and ‘581 with Weineisen 2015.
Regarding trace metal impurities of Fe, Cu, Zn, and, Pb less than or equal to 0.05 ug/GBq, McCann teaches the composition is free of not more than 0.5% radiochemical impurities (col 10, lines 18-22). This means the composition has impurities in the range of 0-0.5%. The claimed range of 0.05 ug/GBq fully lies within this range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
A person of ordinary skill in the art could have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately. Therefore, a person of ordinary skill in the art would have recognized that the results of the combination were predictable. See MPEP 2143(I)(A).
Regarding ascorbic acid from 10-50mg/mL, McCann teaches the composition further comprises about 5-120 mg/mL ascorbic acid (col 9, lines 23-29). The claimed range of 10-50mg/mL lies fully within this range. In such cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding DTPA, McCann teaches a composition further comprising DTPA (col 23, lines 10-14).
Copending Application No. 18/791,300
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/791,300 (reference application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to 177Lu-PSMA I&T with a molar ratio between 1.0:1.0 to 8.0:1.0 of PSMA I&T 177Lu, suitable for use in humans, and stable for at least 72 hours and in some case stability of up to 120 hours, and a pH range between 3.5 and 6.0, and trace metal impurities of Fe, Cu, Zn, and, Pb less than or equal to 0.05 ug/GBq, and DTPA and ascorbic acid.
Conflicting claims teach the composition of 177Lu-PSMA I&T with a radiochemical purity of 95% for up to 120 hours after formulation and a molar ratio range of PSMA I&T to 177Lu from 8.0:1.0 to 11.0:1.0, a pH range from 3.5 to 6.0, DTPA, ascorbic acid, 7 or more cycles of administration in a human, and trace metal impurities of Fe, Cu, Zn, and Pb at or below 0.05 ug/GBq. As to the molar ratios and pH ranges, in cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Copending Application No. 18/204,235
Claims 1-30 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 9, 11-14, 16-20 of copending Application No. 19/204,235 (reference application).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to 177Lu-PSMA I&T with a molar ratio between 1.0:1.0 to 8.0:1.0 of PSMA I&T 177Lu, suitable for use in humans, and stable for at least 72 hours and in some case stability of up to 120 hours, and a pH range between 3.5 and 6.0, and trace metal impurities of Fe, Cu, Zn, and, Pb less than or equal to 0.05 ug/GBq, and DTPA and ascorbic acid.
Conflicting claims teach the composition of 177Lu-PSMA I&T with a radiochemical purity of 95% or higher for up to 120 hours, and a molar ratio of PSMA I&T to 177Lu of 1.0:1.0 to 5.0:1.0, and a pH range of 5.5-7.5, and trace metal impurities of Fe, Cu, Zn, and Pb at or below 0.05 ug/GBq. As to the molar ratio range and the pH range, in cases where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Response to Arguments
Applicants state that claim 1 recites a PSMA I&T to 177Lu molar ratio in the formulated composition of 1.0:1.0 to 8.0:1.0, a final pH of 3.5 to 4.4, Fe metal content of ≤ 0.05 µg/GBq, and suitability for human administration for at least 72 hours after formulation. And, that claims 28 and 30 include similar limitations.
Applicants state Weineisen 2015 does not disclose claimed molar ratio in a formulated composition. And, applicants state Weineisen 2015 has 24.5 MBq of 177Lu reacted with a 4.5-fold molar excess of PSMA I&T (Weineisen 2015, pg 1171, col 2). Applicants state that Weineisen 2015 does not report how much PSMA I&T remains after complexation, processing, purification, recovery, and formulation. Applicants state that this is not a measurement of residual PSMA I&T relative to total 177Lu in the formulated dose. Applicants argue that the construction of the ratio as unchelated PSMA I&T to total 177Lu does not disclose the claimed final-composition ratio.
Respectfully, the applicants’ arguments are not persuasive. The phrase, “formulated composition” that is added to the claim is not defined in the specification. Therefore, any formulation composition, purified or otherwise, reads on the phrase in the claim, as such broadest reasonable interpretation suggests that any prior art have a formulated composition, regardless of degree of complexation, processing, purification, recovery, and formulation conditions, reads on this phrase. Therefore, Weineisen 2015 has the condition of a 4.5-fold molar excess of PSMA I&T to 177Lu need not report how much PSMA I&T remains after complexation, processing, purification, recovery, and formulation. Additionally, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “measurement of residual PSMA I&T relative to total 177Lu”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicants state McCann does not cure these deficiencies in that McCann separately identifies reaction compositions containing ascorbate at pH 4.5-6 and formulation compositions at pH 6-7 (McCann, col 26, lines 52-67). Applicants argue that since the pH 4.5 endpoint argued in the office action is the pH of the intermediate reaction composition, and not the final formulation, McCann does not disclose a formulated composition having the claimed pH of 3.5-4.4. Additionally, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “final formulation”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicants state that McCann does not disclose Fe content in µg/MBq. Additionally, applicants state that 0.5 weight percent radiochemical impurities concerns radiolabeled or degradation species measured as a percentage, not the mass of elemental Fe normalized to radioactivity (McCann, col 10 ,lines 18-22). Applicant argues that these chemically and dimensionally different parameters do not form overlapping ranges, and McCann provides no conversion to the claimed Fe, Cu, Zn, or Pb limits.
Respectfully, the applicants’ arguments are not persuasive. While McCann does not disclose the metal content for Fe, Cu, Zn, or Pb, in µg/MBq it does disclose that there can be 0 µg of the metal in the sample, normalized to the radioactivity. McCann also teaches that the impurities (radioisotopic or chemical) can be 0 in weight percent. In this case, the different parameters form overlapping ranges. In the case where McCann is 0 and there is 0 µg of the metals, the ranges overlap, regardless of the units used to describe that there are no impurities. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). Additionally, the claim does not specify the isotope of the metals. BRI allows for any isotope of the metals (radioisotopic or stable). Therefore, McCann amount of radioisotopic impurities reads on the metal amounts.
The applicant argues the rationale for combining Weineisen 2015 with McCann recites each element would perform the same function after combination does not explain why a person of ordinary skill would have selected Weineisen’s precursor charge, assumed it to be the final-composition ratio, reduced McCann’s final-formulation pH below its evaluated range, controlled elemental Fe to the claimed activity-normalized limit, and reasonably expected the resulting composition to remain suitable for administration for 72 hours since the variables are not independent, interchangeable components.
Respectfully, the applicants’ arguments are not persuasive. While the components may not be independent, interchangeable components, the supreme court KSR rationale A teaches that a finding that the prior art included each element claimed although not necessarily in a single embodiment or reference, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements in a single prior art reference is considered obvious. See MPEP 2143(I)(A). Additionally, the final-composition ratio is not explicitly claimed. The phrase formulated composition does not require that the composition be in final form. However, purely arguendo, Weineisen 2015 teaches the formulated composition is used in humans (pg 1173, col 1, para 1-2). Additionally, In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “final-composition ratio”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant argues neither reference identifies the claimed final-composition ratio, pH range, or elemental Fe level for the claimed 72-hour composition.
Respectfully, the applicants’ arguments are not persuasive. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Additionally, In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., final-composition ratio) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicants’ argue that claim 28 is patentable for the same reasons as claim 1 in that Weineisen 2015 and McCann fail to teach or suggest a formulated composition having the claimed ratio together with RCP of at least 95% at 72 hours.
Respectifully, applicants’ arguments are not persuasive. In that the combined teachings of Weineisen 2015 and McCann teach the formulation composition (Weineisen 2015, pg 1171, col 2, Synthesis and Radiolabeling, para 2, lines 4-7) and a RCP of at least 95% at 72 hours (McCann, col 10, lines 1-3).
Applicants’ argue claim 30 molar ratio of the claimed final-composition range is outside the prior art 4.5:1.0 range and that the prior art of McCann does not disclose the final pH nor the elemental-metal limits.
Respectfully, the applicants’ arguments are not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “final-composition” and “final pH”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). With respect to the elemental metal limits, McCann teaches radio and chemical impurities (col 30, lines 18-22). This reads on any radio or any chemical impurity. Therefore, when McCann says the chemical impurities can be 0 wt% this reads on the amount of the elemental metal impurities, Fe, Cu, Zn, and Pb.
Applicants argue that claims 2-27 and 29 are patentable since the depend on claims not overcome by the deficiencies of Weineisen 2015 and McCann.
Respectfully, the applicants’ argument is not persuasive. Please see above for the reasons why claims 1, 28, and 30 are rejected.
Applicant states that claims 11-12 are rejected further in view of Weineisen 2014. Applicant argues that claims 11-12 are patentable for the same reasons as claim 1 and that Weineisen fails to overcome the deficiencies of Weineisen 2015 and McCann.
Respectfully, applicants’ arguments are not persuasive. As evidenced by Weineisen 2014, adjusting the molar ratio of PSMA I&T to 177Lu can be successful even if the PSMA I&T to 177Lu is adjusted to 1.0:2.5 (Weineisen 2014, pg 5, col 2, para 8, line 2). Furthermore, ranges can be disclosed in multiple prior art references instead of in a single prior art, this provides evidence that a molar range from 4.5:1.0 to 1.0:2.5 is workable. See MPEP 2144.05(I). With respect to a difference in isotope causing a difference in teaching, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. In the present case, formulation of compounds with the same structures but different isotopes can have the same utility in terms of serving as a composition for analysis. Additionally, Weineisen 2014 suggests 177Lu (Weineisen 2014, pg 2, col 1, para 3, lines 6-13). The claimed amount of 2.0:1.0 lies inside the prior art range of 4.5:1.0 to 1.0:2.5. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Applicant argues that since Weineisen 2014 does not claim 177Lu and a composition having a 72 hour suitability, it does not cure the deficiencies of the references.
Respectfully, the appicants’ arguments are not persuasive. Weineisen 2014 suggests 177Lu (Weineisen 2014, pg 2, col 1, para 3, lines 6-13; pg 10, col 2, para 2, lines 1-4). And McCann teaches a 72 hour suitability. However, Weineisen suggests a period of time longer than 48 hours for 177Lu bearing compositions (pg 10, col 2, para 2, lines 1-6). Additionally, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicants state claim 15 is rejected in view of Weineisen 2015 supplementary information. Applicants argue that Weineisen Supplementary do not overcome the deficiencies of Weineisen 2015 and McCann.
Respectfully, the applicants’ arguments are unpersuasive. Please see above for the reasons why claims 1, 28, and 30 are rejected.
The Applicants acknowledge Weineisen Supplementary discloses 150-200 µg PSMA I&T for a 6-8 GBq preparation. Applicants state the amount is precursor used in preparation, not an amount of unchelated PSMA I&T remaining in the final dose. Applicants argue neither reference teaches the resulting endpoint combinations, and Weineisen Supplementary does not cure the deficiencies of the rejection of claim 1.
Respectfully, the applicants’ arguments are not persuasive. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “unchelated PSMA I&T remaining in the final dose”, “endpoint combinations”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant states that the office action does not provide a limitation-by-limitation comparison for each amended claim, and instead relies on broad summaries of the conflicting claims together with Weineisen and McCann. The applicants argue the secondary references do not supply the missing limitations pointed out in the office action, particularly because Weiensen does not disclose the ratio in the formulation composition and McCann’s radiochemical-impurity percentage does not disclose element-metal content in µg/GBq.
Respecfully, the applicants’ arguments are unpersuasive. Please see above for why the 103 rejections based on the combined teachings of Weineisen 2015, McCann, and Weineisen Supplementary, and Weineisen 2014 are sustained. With respect to Weineisen does not disclose the ratio in the formulated composition, Weineisen 2015 teaches teaches a composition comprising [177Lu]Lu-PSMA I&T (pg 1171, col 1, para 6, lines 6-8) wherein the molar ratio of PSMA I&T to 177Lu is 4.5:1.0 (pg 1171, col 2, Synthesis and Radiolabeling, para 2, lines 4-7). With respect to McCann, McCann teaches the composition is has 0-5 wt% chemical impurities (col 30, lines 18-22). This means the composition has impurities in the range of 0-5 wt% chemical impurities reads on no Fe, Cu, Zn, and Pb metal present.
The applicants argue that the ratios are sufficiently distinct because the ranges of 8.0:1.0 to 11.0:1.0 of 18/791,300 does not overlap with the instant claimed range of 2.0:1.0 to 6.0:1.0 in instant claim 28 or 2.0:1.0 to 4.0:1.0 range of instant claim 30 and only shares the endpoint of instant claim 1. The applicants argue that because a reason to select a value within the range with the Fe limitation, the rejection is insufficient.
Respectfully, the applicants’ arguments are not persuasive. Molar ratios are ratios of concentrations. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05(II)(A).
The applicants argue that 18/204,235 have a pH range that is outside the amended final pH range of 3.5-4.4 and the rejection should be withdrawn.
Respectfully, the applicants’ arguments are not persuasive. The pH is a measurement of hydrogen ion concentration. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05(II)(A).
The rejections are maintained.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Evan M Lewoczko whose telephone number is (571)272-9830. The examiner can normally be reached Monday-Friday 9-5PM.
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/EVAN M LEWOCZKO/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
