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 1-29, filed 10/4/2022, are acknowledged. Claims 1-29 are pending and considered on the merits below.
Information Disclosure Statement
The Information Disclosure Statements filed on 5/3/2023 and 10/23/2025 are in compliance with the provisions of 37 CFR 1.97 and have been considered. An initialed copy of the Form 1449 is enclosed herewith.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, the limitation “Yb” (line 8) has lack of antecedent basis. For examination purposes the examiner interprets that it takes antecedent basis from Yb2O3.
Further regarding claim 1, the limitation “collecting Lu-177 having passed through the first resin cartridge… onto a first collection column..” (lines 11-13) is indefinite because there is lack of antecedent basis for “Lu-177” and the phrasing makes it unclear as to which piece of the device is positioned where. For examination purposes the examiner interprets that the limitation reads:
“collecting the Lu-177, that was passed through the first resin cartridge containing dipentyl pentylphosphonate, by capturing it onto a first collection column having a resin containing tetraoctyl diglycolamide (DGA) “
Lines 20-23 and 26-28 of claim 1 the same issues.
Regarding claim 12, the limitation “loading” is indefinite because it is unclear which loading step of claim 1 it is referring to. For examination purposes the examiner interprets it is either step.
Dependent claims follow the same reasoning.
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) 1-8, 10-22, 24-29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Horowitz et al. (Applied Radiation and Isotopes 63 (2005) 23–36, provided on the IDS on 5/3/2023).
Regarding claim 1, Horowitz describes a method of making Lu-177 (abstract), the method comprising:
dissolving an enriched Yb2O3 (figure 10 “Dissolve Irradiated Yb2O3 Target”),
optionally processing the dissolved enriched Yb2O3 in a pre-coarse column containing resin prepared from (2-ethyl-1-hexyl)phosphonic acid mono(2-ethyl-1- hexyl)ester (HEH[EHP]) (OPTIONAL LIMITATION);
loading the dissolved enriched Yb2O3 on a first chromatographic guard column containing resin prepared from (2-ethyl-1-hexyl)phosphonic acid mono(2-ethyl-1- hexyl)ester (HEH[EHP]) to separate Lu-177 from Yb (figure 10 “LN2” and page 25 “LN2 resin, was prepared from (2-ethyl-1-hexyl)phosphonic acid mono (2-ethyl-1-hexyl) ester (HEH[EHP])”);
collecting Lu-177 having passed through the first resin cartridge containing dipentyl pentylphosphonate onto a first collection column having resin containing tetraoctyl diglycolamide (DGA) (figure 10 “DGA #1”));
loading an exiting stream from the first collection column having resin containing DGA on a second chromatographic guard column containing resin prepared from (2- ethyl-1-hexyl)phosphonic acid mono(2-ethyl-1-hexyl)ester (HEH[EHP]) to separate Lu- 177 from Yb (figures 10-11 “(6)” to “LN2”);
collecting Lu-177 having passed through the second resin cartridge containing dipentyl pentylphosphonate onto a second collection column having resin containing tetraoctyl diglycolamide (DGA) (figure 11 “DGA #2”);
passing a second separation of a stream exiting from the second chromatographic guard column through a third resin cartridge containing dipentyl pentylphosphonate (figure 13 and page 30 “UTEVA resin contains the extractant diamyl amylphosphonate (dipentyl pentylphosphonate) as a stationary phase,… UTEVA guard column on top of the DGA resin column.”); and
collecting Lu-177 having passed through the third resin cartridge containing dipentyl pentylphosphonate onto a third collection column having resin containing tetraoctyl diglycolamide (DGA) (figure 13 and page 30 “UTEVA resin contains the extractant diamyl amylphosphonate (dipentyl pentylphosphonate) as a stationary phase,… UTEVA guard column on top of the DGA resin column.”).
However Horowitz is silent to passing a first separation of a stream exiting from the first chromatographic guard column through a first resin cartridge containing dipentyl pentylphosphonate (figure 13 and page 30 “UTEVA resin contains the extractant diamyl amylphosphonate (dipentyl pentylphosphonate) as a stationary phase,… UTEVA guard column on top of the DGA resin column.”) and passing a first separation of a stream exiting from the second chromatographic guard column through a second resin cartridge containing dipentyl pentylphosphonate (figure 13 and page 30 “UTEVA resin contains the extractant diamyl amylphosphonate (dipentyl pentylphosphonate) as a stationary phase,… UTEVA guard column on top of the DGA resin column.
Horowitz does describe “We found that by placing a small quantity (1–2 mL) of UTEVA resin at the top of the DGA resin column, the problem with HEH[EHP] leachate is obviated.” (page 30). This suggests motivation to use dipentyl pentylphosphonate (diamyl amylphosphonate) prior to DGA as it would provide a solution to the problem with HEH[EHP].
Therefore it would have been obvious to one skilled in the art at the time the invention was filed to incorporate additional passing of the streams through dipentyl pentylphosphonate prior to the DGA as suggested by Horowitz as this would provide a solution to the problem with HEH[EHP].
Regarding claim 2, the combination described above describes the method according to claim 1, further comprising passing a stream exiting from the third collection column having resin containing DGA through a pre-filter column for trace organics removal (Horowitz: page 32 “small anion-exchange column on the chloride cycle is shown in the final step. The purpose of this column is to eliminate all traces of nitrate ion.”).
Regarding claim 3, the combination described above describes the method according to claim 1, further comprising evaporating (Horowitz: page 25 “stirred for 1 h on a rotary evaporator”).
Regarding claim 4, the combination described above describes the method according to claim 1, further comprising conducting pyrolysis (page 27 “0.1M HCl” Examiner’s note: the specification indicates that high acidify causes pyrolysis. [0015] “pyrolysis by incorporating higher normality acid, such as higher than 0.045N HCl.”).
Regarding claim 5, the combination described above describes the method according to claim 1, further comprising reconstituting (page 27 “column was then fully stripped with 4.0M HNO3 and reconditioned (reconstituting)”).
Regarding claim 6, the combination described above describes the method according to claim 1, further comprising conducting neutron irradiation of enriched Yb2O3 prior to dissolution (Horowitz: page 29 “neutron irradiation of macro quantities of 176Yb” in Yb2O3).
Regarding claim 7, the combination described above describes the method according to claim 6, further comprising retrieval of the enriched Yb203 prior to dissolution (Horowitz: figure 10 “Dissolve Irradiated Yb2O3 Target” i.e. would have been retrived).
Regarding claim 8, the combination described above describes the method according to claim 6, further comprising purifying the enriched Yb2O3 (Horowitz: figure 10 “Waste solution contains most metal ion impurities”).
Regarding claim 10, the combination described above describes the method according to claim 1, wherein the dissolved enriched Yb203 is loaded on the first chromatographic guard column with 0.001 N to 0.5 N HNO3 (Horowitz: figure 10 “0.1 M HNO3”).
Regarding claim 11, the combination described above describes the method according to claim 1, wherein the first chromatographic guard column has a bed volume of about 29 cm3 to about 68 cm3 (Horowitz: figure 10 “150 cm3 B.V.” is about 68 cm3).
Regarding claim 12, the combination described above describes the method according to claim 10, wherein loading is followed by a first rinse with HNO3 (Horowitz: figure 10 “Rinse 0.1 M HNO3”).
Regarding claim 13, the combination described above describes the method according to claim 12, wherein the first rinse with HNO3 is in a range of 0.01 N to 0.5 N HNO3 (Horowitz: figure 10 “Rinse 0.1 M HNO3”).
Regarding claim 14, the combination described above describes the method according to claim 12, wherein the first rinse is followed by a second rinse with HNO3 (Horowitz: figure 10 “4 Bed Volumes (B.V.) of 1.5 M HNO3”).
Regarding claim 15, the combination described above describes the method according to claim 14, wherein the second rinse with HNO3 is in a range of 0.5N to 2N HNO3 (Horowitz: figure 10 “4 Bed Volumes (B.V.) of 1.5 M HNO3”).
Regarding claim 16, the combination described above describes the method according to claim 14, wherein the second rinse produces a combined Yb fraction with 0.5N to 2N HNO3 and a Lu/trace Yb fraction with 2N to 6N HNO3 passing into the first chromatographic guard column (Horowitz: Horowitz: figure 10 “3 B.V. of 4 M HNO3).
Regarding claim 17, the combination described above describes the method according to claim 16, wherein the Lu/trace fraction passes in the first separation of the stream exiting from the first chromatographic guard column through the first resin cartridge containing dipentyl pentylphosphonate and onto the first collection column having resin containing tetraoctyl diglycolamide (DGA) (Horowitz: figure 10, in the combination of claim 1 the first resin cartridge contains dipentyl pentylphosphonate above the first collection column having resin containing tetraoctyl diglycolamide (DGA)).
Regarding claim 18, the combination described above describes the method according to claim 1, wherein the exiting stream from the first collection column contains a Lu/trace fraction in HCl and trace HNO3 (Horowitz: figure 10 “Lu (13 Ci), Yb (30 mg) in (100 mL) of 0.05 M HCl + trace HNO3”).
Regarding claim 19, the combination described above describes the method according to claim 1, wherein the second chromatographic guard column has a bed volume in a range of about 29 cm3 to about 68 cm3 (Horowitz: figure 11 “LN2 68 cm3 B.V.”).
Regarding claim 20, the combination described above describes the method according to claim 1, wherein the exiting stream from the first collection column having resin containing DGA combines with a first rinse with 0.5N to 2N HNO3 and a second rinse with 0.01 N to 0.5 N HNO3 prior to loading on the second chromatographic guard column (Horowitz: figure 10 “(39 mL) Rinse 0.1 M HNO3 (100 mL) Strip 0.05 M HCl”).
Regarding claim 21, the combination described above describes the method according to claim 1, wherein a flow containing a trace Yb fraction with 0.5N to 2N HNO3 combines with a Lu fraction with 2N to 6N HNO3, and the combined flow enters the second chromatographic guard column (Horowitz: figure 10 “(39 mL) Rinse 0.1 M HNO3 (100 mL) Strip 0.05 M HCl”).
Regarding claim 22, the combination described above describes the method according to claim 1, wherein the stream exiting the second chromatographic guard column enters a valve separating the exiting flow into at least the first separation and the second separation (Horowitz: figure 11 shows a 3 way separation after the LN2 68 cm3 B.V (second chromatographic guard column) indicating a valve).
Regarding claim 24, the combination described above describes the method according to claim 1, wherein a rinse with 0.01 N to 0.5 N HNO3 and a Lu fraction with 0.01N to 0.5N HCl is added to the second resin cartridge containing dipentyl pentylphosphonate (Horowitz: figure 13 “(9 mL) Rinse 0.1 M HNO3 (24 mL) Strip 0.05 M HCl”).
Regarding claim 25, the combination described above describes the method according to claim 1, wherein the stream exiting the second collection column having resin containing tetraoctyl diglycolamide (DGA) enters the second chromatographic guard column (Horowitz: figure 12 “Yb Fraction <0.2 mg (203 mL)” back to “(3)” figure 11, and then back to the second chromatographic guard column.).
Regarding claim 26, the combination described above describes the method according to claim 1, wherein a rinse with 0.01 N to 0.5 N HNO3 and a Lu fraction with 0.01N to 0.5N HCl is added to the third resin cartridge containing dipentyl pentylphosphonate (Horowitz: figure 13 “DGA #3 3 cm3 B.V.”).
Regarding claim 27, the combination described above describes the method according to claim 1, wherein a stream containing a high purity Lu fraction in 0.01N to 0.5N HCl and trace HNO3 exits from the third collection column having resin containing tetraoctyl diglycolamide (DGA) (Horowitz: figure 11 “Lu (12 Ci), Yb (<0.2 mg) (48 mL) of 0.05 M HCl + trace HNO3”).
Regarding claim 28, the combination described above describes the method according to claim 27, wherein the stream containing the high purity Lu fraction in 0.01N to 0.5N HCl and trace HNO3 goes to a pre-filter column (Horowitz: figure 12 “Lu Fraction (203 mL) 11 Ci (pre-filter)”).
Regarding claim 29, the combination described above describes the method according to claim 1, further comprising recirculation with at least one chromatographic guard column containing resin prepared from (2-ethyl-i- hexyl)phosphonic acid mono(2-ethyl-1-hexyl)ester (HEH[EHP]) (Horowitz: page 26 “column was thermostated at 25 or 50 °C using a recirculating water/ethylene glycol bath.”).
Allowable Subject Matter
Claim 9 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: References above describe most of the limitations of claim 9, however fail to teach or suggest wherein the dissolved enriched Yb2O3 is loaded onto the first chromatographic guard column at a temperature of 150 °C to 250 °C.
None of the prior art discovered describes all the limitations alone or in combination, thus the prior art fails to teach or suggest all the limitations of claim 9.
Claim 23 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: References above describe most of the limitations of claim 23, however fail to teach or suggest wherein the valve is controlled by a gamma spectroscopy detector.
None of the prior art discovered describes all the limitations alone or in combination, thus the prior art fails to teach or suggest all the limitations of claim 23.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY R BERKELEY whose telephone number is (571)272-9831. The examiner can normally be reached M-Th 9-6.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Elizabeth Robinson can be reached at 571-272-7129. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMILY R. BERKELEY/
Examiner
Art Unit 1796
/ELIZABETH A ROBINSON/Supervisory Patent Examiner, Art Unit 1796