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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 20, 2026 has been entered.
Response to Arguments
Applicant's arguments filed February 20, 2026 have been fully considered but they are not persuasive.
On page 8 of the Remarks section, as indicated by the page number at the bottom of each page, Applicant discusses the previous objection and amendments made to obviate it. The Examiner has withdrawn this objection as a result.
On pages 8-9, Applicant argues against the previous 103 prior art rejection. Applicant argues that “the claimed method differs fundamentally from Torgue in structure and principle of operation”. Applicant summarizes the claimed invention, then goes on to summarize the invention of Torgue. Applicant argues that Torgue discloses a generator where lead-212, a daughter product, is eluted for use as the parent radioisotope is immobilized, noting that this system is dependent on the decay chain, and extracts the daughter radioisotope, not the parent. Applicant argues that Torgue is a decay-based daughter generator, not a parent-isotope recycling system. Applicant also argues that Torgue retains the parent radionuclide permanently on a solid support. The Examiner notes however that while Torgue does not disclose this claimed step, other previously used prior art references disclose the argued features instead. For example, previously used secondary reference Fassbender et al., (“Fassbender”, US 2015/0292061), discloses this feature allowing the parent radioisotope to be complexed and removed, (See paragraph [0023], [0060], Fassbender). Furthermore, the Examiner notes that other previously used secondary reference Taylor et al., (“Taylor”, US 5,966,583), explicitly discloses the feature of recycling parent-isotopes, (See Abstract, and See column 2, lines 40-53, Taylor). Thus, the Examiner notes that these arguments are piecemeal analysis, and are thus unpersuasive. In response to applicant's arguments against the references individually, 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).
Applicant continues to argue that Torgue’s purpose would be undermined if it were to be modified in the manner laid out by Applicant and its invention. Applicant asserts that its invention allows continued use of the parent isotope in a new generator, and teaches a method of intentionally remobilizing and refixing the parent, while Torgue only fixes its parent isotope. The Examiner notes however that Torgue does not explicitly teach away from modifying its invention in any manner such as that demonstrated in the current rejection, and that there can be reasons to modify to recover the parent radioisotope such as recycling and reuse of the system to carry out again which is already laid out in Taylor, (See Abstract, and See column 2, lines 40-53, Taylor). The Examiner maintains that the combination of Torgue and Taylor carries out the same function as argued by Applicant, and that there is no statement in the references stating they teach away. The Examiner finds this argument unpersuasive.
On page 10, Applicant argues that modifying Torgue to elute the parent isotope, not its daughter, would undermine the purpose and destroy the functionality of the reference. The Examiner notes that the combination of references would still yield a daughter radioisotope for production, but also would present a way to reuse the parent isotope for recycling and regeneration for subsequent performances of this process, (See Abstract, and See column 2, lines 40-53, Taylor). Applicant argues that Torgue teaches away from doing so. The Examiner notes though that Torgue never explicitly states its system cannot be modified to recover or reuse the parent radioisotope. The Examiner maintains that Torgue does not explicitly teach away from this sort of modification as alleged by Applicant.
Applicant continues to argue that there is not a motivation to modify Torgue in the manner required to arrive at Applicant’s method. Here, the Examiner notes that Applicant has not explicitly addressed the rationales already provided in the combination of references, particularly as in Fassbender as providing additional washing allows the method “to remove additional thorium(IV) from the column” (See paragraph [0039] & [0041], Fassbender), and “to provide a source of [parent isotope] for additional….generators”, (See Abstract, Taylor), such that it can “minimize what has previously been a radioactive waste stream and convert at least a portion of it into a useful product by recycling [parent isotope] activity from spent [parent/daughter radioisotope] generators”, (See column 2, lines 13-17, Taylor). These motivations are presented and already known in the art to carry out, for the benefits of removing more eluate and/or the desired radioisotope, and limiting a waste stream while recycling/reusing spent parent/daughter radioisotope generators. The Examiner finds these arguments unpersuasive.
On pages 10-11, Applicant argues that secondary reference Fassbender does not teach dissociating a complexed parent isotope before column loading. The Examiner notes that it is not clamed to dissociate the isotope before “column loading”. The Examiner notes that the Abstract and various paragraphs in Fassbender demonstrate that different complementary complexing/decomplexing agents are used to remove different isotopes from the stationary phase, (See Abstract, paragraph, [0023], [0030], [0041], [0060], Fassbender). The Examiner notes that these agents or solutions are used for specific columns, the order of loading is not claimed or required. For these reasons, the Examiner finds Applicant’s remarks unpersuasive.
On pages 10-11, Applicant also argues against Taylor because it uses mineral acid and cation exchange resins followed by multiple purification steps for recovery of strontium-82, not chelation/de-chelation chemistry. The Examiner notes that column 3, lines 38-59, of Taylor, explicitly demonstrate using mineral acids which include acids such as hydrochloric acid, nitric acid and more, which are the same acids used for acidification and washing of the eluate as in the claimed invention. The use of these acids in Taylor is used for elution of the parent isotope to reuse the generator again. The Examiner notes that separating these isotopes from the generator relies upon chelation/de-chelation chemistry. Further purifying the obtained isotope is not contradictory with reusing a spent generator and using a second generator. Thus, the Examiner finds this argument unpersuasive. The Examiner also notes that Fassbender is already used to disclose the complexing and decomplexing process, not Taylor. Thus, this argument by Applicant is piecemeal analysis. In response to applicant's arguments against the references individually, 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).
On pages 11-12, Applicant argues against the motivation statements relied upon in the prior art rejections. Applicant argues that using the rationale of recycling the parent radionuclide to reduce waste, minimize cost, or improve efficiency, is allegedly not sufficient and is allegedly not articulated reasoning with rational underpinning. The Examiner notes that these various rationales already cited are statements of rational underpinning indicating that incorporation of the disclosed elements would result in improving efficiency and reducing waste for recycling. These rationales map onto the KSR principles laid out in MPEP 2143 in which “the combination of references results in a product or process that is more desirable, for example because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient,” as in rationale G. which is “some teaching suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference teachings to arrive at the claimed invention”. The Examiner finds Applicant’s characterization of the motivations provided unpersuasive since they are direct examples of rationale G for establishing a prima facie case of obviousness.
On page 12, Applicant continues to argue that modifying Torgue to remove the parent isotope would destroy its utility. However, the Examiner takes the position that removing the parent isotope for a spent generator to recycle or reuse the generator, and eliminate a waste stream as put forth in Taylor does not contradict the ability of Torgue to separate the parent and daughter radioisotope in the first place. The Examiner finds this remark unpersuasive again.
On page 12, the remainder of Applicant’s remarks directed against the previous prior art rejections of dependent claims are considered moot because they do not present any more specific arguments against the references.
On pages 12-14, Applicant argues that the previous combination of references does not disclose the newly added dependent Claims 20-24. Applicant argues that Torgue does not disclose Claim 20. However, the Examiner notes that Taylor discloses this limitation instead, (See Abstract, and See column 2, lines 40-53, Taylor; this process describes obtaining the parent in each generator, not the daughter). Applicant argues that the references do not disclose Claim 21. Applicant argues that Fassbender and Taylor do not disclose this claim. However, the Examiner takes the position that Fassbender does disclose this claim because it demonstrates that different acids are used to complex and decomplex different radioisotopes from each other, leaving the other radioisotopes behind until a different agent is used for those radioisotopes, (See Abstract and See paragraph [0030], [0041], Fassbender). Applicant argues that Taylor and Fassbender do not disclose Claim 22. The Examiner notes that Torgue discloses this limitation instead, (See paragraph [0081] & [0083], Torgue, chromatography column 28 is the new generator/second stationary phase; and See paragraph [0023], [0060], Fassbender). Applicant argues that the references do not disclose Claim 23. However, the Examiner notes that Fassbender discloses this claim instead, (See paragraph [0030], Fassbender), and the complex dissociates, (See paragraph [0023], [0030], [0060], Fassbender). Applicant argues that the references, particularly Torgue, do not disclose Claim 24. However, the Examiner finds that Drera discloses this limitation instead, (See column 2, lines 33-67, column 3, lines 1-5, Drera).
Specification
The abstract of the disclosure is objected to because the first sentence lacks a subject-verb structure. Correction is required. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 20-22 & 24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 20 recites the limitation “the method does not include the collection or elution of a daughter radionuclide for use”. This limitation does not appear to be explicitly supported in the Specification. Since it is a negative limitation, explicit support or demonstration that the invention does not use or employ collection or elution of the daughter radionuclide for use is required. Thus, the Examiner considers this limitation to be new matter.
Claim 21 recites the limitation “the second stationary phase is selected to fix the decomplexed parent radioisotope while permitting the free complexing agent to pass through without binding”. This limitation does not appear to be explicitly supported in the Specification where the free complexing agent would pass through at the same time as the decomplexed parent radioisotope is fixed. Thus, the Examiner considers this limitation to be new matter.
Claim 22 recites the limitation “wherein no purification step is performed between dissociating the complexes of the parent radioisotope and fixing the parent radioisotope on the second stationary phase”. This limitation does not appear to be explicitly supported in the Specification. Since it is a negative limitation, explicit support or demonstration that the invention does not carry out or perform a purification step when it dissociates complexes and fixes the parent radioisotope is required. Thus, the Examiner considers this limitation to be new matter.
Claim 24 recites the limitation “the method does not include fixing or recovering any decay product of the parent radioisotope”. This limitation does not appear to be explicitly supported in the Specification. Since it is a negative limitation, explicit support or demonstration that the invention does not carry out or perform fixing or recovering any decay product is required. Thus, the Examiner considers this limitation to be new matter.
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) 1-4, 6-13, 17, 18 & 20-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Torgue et al., (“Torgue”, US 2015/0170776), in view of Horwitz et al., (“Horwitz”, US 2003/0219366), in view of Fassbender et al., (“Fassbender”, US 2015/0292061), in further view of Taylor et al., (“Taylor”, US 5,966,583).
Claims 1-4, 6-13, 17, 18 & 20-23 are directed to a method for transferring a radioisotope, a method type invention group.
Regarding Claims 1-4, 6-13, 17, 18 & 20-23, Torgue discloses a method for obtaining a new generator from a used generator, the used generator comprising a parent radioactive isotope which is a radioactive isotope of thorium, radium, lead, bismuth or uranium, (See paragraph [0077]), and which is fixed on a first stationary phase contained in a first chromatography column, (See paragraph [0078]), and the new generator comprising the radioisotope fixed on a second stationary phase contained in a second chromatography column, (See paragraph [0081] & [0083]), said method comprising: a) eluting the radioisotope from the used generator, wherein eluting comprising circulating in the first chromatography column, a first aqueous solution A1 to obtain an aqueous eluate, (See paragraph [0100], [0119] & [0120]), part of b) to obtain the radioisotope in a decomplexed form, (See paragraph [0120]); c) preparing the new generator by fixing the radioisotope present in the aqueous eluate obtained from step (b) on the second stationary phase contained in the second chromatography column, wherein fixing the radioisotope comprises circulating the aqueous eluate obtained from step (b) in the second chromatography column, the second stationary phase being suitable for fixing the radioisotope without fixing the impurity, (See paragraph [0123] & [0126]); and washing at least once with a second aqueous solution suitable for eluting the impurities in the free form without eluting the radioisotope from the second stationary phase, (See paragraph [0130] & [0131]); whereby the new generator is obtained, (See paragraph [0130] & [0131])
Torgue does not explicitly disclose the new generator comprising the parent radioisotope, eluting the parent isotope, dissociating the parent isotope, fixing the parent isotope for the new generator; comprising an agent complexing the radioisotope, where the aqueous eluate comprises complexes of the radioisotope, b) dissociating the complexes of the radioisotope present in the aqueous eluate to obtain the radioisotope in a decomplexed form and the complexing agent in a free form, wherein dissociating the complexes of the radioisotope comprises modifying the pH of the aqueous eluate, eluting the complexing agent in the free form.
Fassbender discloses a method, (See Abstract, See paragraph [0010], Fassbender), comprising an agent complexing the radioisotope, where the aqueous eluate comprises complexes of the radioisotope, (See paragraph [0030], Fassbender), , b) dissociating the complexes of the radioisotope present in the aqueous eluate to obtain the radioisotope in a decomplexed form and the complexing agent in a free form, wherein dissociating the complexes of the radioisotope comprises modifying the pH of the aqueous eluate, eluting the complexing agent in the free form, (See paragraph [0023], [0060], Fassbender). Additional features of this disclosure are also included in the combination and claim mapped to in the Additional Disclosures section below.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of Torgue by incorporating comprising an agent complexing the radioisotope, where the aqueous eluate comprises complexes of the radioisotope, b) dissociating the complexes of the radioisotope present in the aqueous eluate to obtain the radioisotope in a decomplexed form and the complexing agent in a free form, wherein dissociating the complexes of the radioisotope comprises modifying the pH of the aqueous eluate, eluting the complexing agent in the free form as in Fassbender because Torgue discusses “the radioactive decay chain of thorium 232….also…radium 224” and actinium (Ac), (See paragraph [0009], and Figure 1, Torgue), and Fassbender notes that “recovery of actinium involves separating actinium from thorium, which is present as Th(IV)” so “converting the soluble Th(IV) to soluble anionic complexes”, (See paragraph [0030], Fassbender), enables “the solution of anionic complexes of thorium(IV) [to be] then passed through a column” which “elute” while the radionuclides “retained…are those that did not form anionic complexes” such as “radium (II)”, (See paragraph [0031], Fassbender). Furthermore, providing additional washing allows the method “to remove additional thorium(IV) from the column” (See paragraph [0039] & [0041], Fassbender). Thus, Fassbender provides a “method for separating radium…from proton-irradiated targets of thorium [that is] desirable”, (See paragraph [0010], Fassbender), to obtain “radiological purity…such as radium”, (See paragraph [0029], Torgue).
Modified Torgue does not explicitly disclose that the used generator includes a first chromatography column.
Horwitz discloses a method using a first chromatography column, (See paragraph [0058], Horwitz). Additional features of this embodiment are included as part of the overall combination and claim mapped to in the Additional Disclosures section below.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Torgue by incorporating that the used generator comprises a first chromatography column as in Horwitz in order to obtain “an ideal generator…[that] should provide operational simplicity and convenience as well as reliable production of the theoretical yield of the daughter radionuclide having high chemical and radionuclidic purity”, (See paragraph [0034], Horwitz), while providing “better chromatographic operating performance”, (See paragraph [0041], Horwitz).
Modified Torgue does not explicitly disclose the new generator comprising the parent radioisotope, eluting the parent isotope, dissociating the parent isotope, fixing the parent isotope for the new generator.
Taylor discloses the new generator comprising the parent radioisotope, eluting the parent isotope, dissociating the parent isotope, fixing the parent isotope for the new generator, (See Abstract, and See column 2, lines 40-53).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Torgue by incorporating the new generator comprising the parent radioisotope, eluting the parent isotope, dissociating the parent isotope, fixing the parent isotope for the new generator as in Taylor in order to recover the parent isotope “to provide a source of [parent isotope] for additional….generators”, (See Abstract, Taylor), such that it can “minimize what has previously been a radioactive waste stream and convert at least a portion of it into a useful product by recycling [parent isotope] activity from spent [parent/daughter radioisotope] generators”, (See column 2, lines 13-17, Taylor).
Additional Disclosures Included:
Claim 2: The method of claim 1, wherein the complexing agent complexing the radioisotope is an aminopolycarboxylic acid or an aminopolycarboxylic acid salt, (See paragraph [0030], Fassbender).
Claim 3: The method of claim 2, wherein the aminopolycarboxylic acid is nitrilotriacetic acid, ethylenediaminetetraacetic acid or diethylenetriaminepentaacetic acid, (See paragraph [0030], Fassbender).
Claim 4: The method of claim 1, wherein the first aqueous solution comprises from 10 mmol/L to 100 mmol/L of ethylenediaminetetraacetic acid or a salt thereof and has a pH of 4 to 8, (See paragraph [0030], Fassbender; A disclosed value of 0.1 M anticipates the claimed range at 100 mmol/L and a disclosed range of pH of 1 to 6 anticipates the claimed range from 4-6).
Claim 6: The method of claim 1, wherein modifying the pH of the aqueous eluate is an acidification to bring the pH of the aqueous eluate equal to or less than 1, (See paragraph [0030], Fassbender; Fassbender discloses adding acid to solution at a disclosed pH value of 1).
Claim 7: The method of claim 6, wherein the acidification of the aqueous eluate comprises an addition of an acid to the aqueous eluate, (See paragraph [0030], Fassbender; Fassbender discloses adding acid to solution at a disclosed pH value of 1).
Claim 8: The method of claim 6, wherein the acidification of the aqueous eluate comprises at least one washing of the first stationary phase with an acidic aqueous solution and an addition of all or part of the acidic aqueous solution issued from the at least one washing to the aqueous eluate, (See paragraph [0054], Horwitz).
Claim 9: The method of claim 8, wherein the acidic aqueous solution comprises from 0.01 mol/L to 0.1 mol/L of nitric acid or from 0.1 mol/L to 1 mol/L of hydrochloric acid, (See paragraph [0054], Horwitz; Horwitz discloses/anticipates a claimed value of 0.2 M HCl).
Claim 10: The method of claim 1, wherein the second aqueous solution comprises from 0.5 mol/L to 4 mol/L of nitric acid or from 2 mol/L to 4 mol/L of hydrochloric acid, (See paragraph [0056], Horwitz; Horwitz discloses/anticipates the claimed value of 2 M HCl).
Claim 11: The method of claim 1, further comprising, a), a step of conditioning the first stationary phase, (See paragraph [0133], [0134], Horwitz; See paragraph [0056], Horwitz, “pre-equilibration”).
Claim 12: The method of claim 1, wherein the first stationary phase consists of a first stationary phase material, the second stationary phase consists of a second stationary phase material and the first and second stationary phase materials are identical, (See paragraph [0058], Horwitz; Examiner interprets that a plurality of second separation media can be used, with those media being in separate or the same guard columns, such that two columns with the second separation media are used and the same).
Claim 13: The method of claim 1, wherein the first stationary phase consists of a first stationary phase material, the second stationary phase consists of a second stationary phase material and the first and second stationary phase materials are different, (See paragraph [0058], Horwitz; Examiner selects the first separation media with a greater selectivity for the daughter in one column, and the second separation media with a greater selectivity for the parent in a second/guard column).
Claim 17: The method of claim 3, wherein the aminopolycarboxylic acid is ethylenediaminetetraacetic acid, (See paragraph [0030], Fassbender).
Claim 18: The method of claim 7, wherein the acid is nitric or hydrochloric acid, (See paragraph [0023], [0060], Fassbender).
Claim 20: The method of claim 1, wherein the parent radioisotope in the new generator is identical to the parent radioisotope eluted from the used generator, and the method does not include the collection or elution of a daughter radionuclide for use, (See Abstract, and See column 2, lines 40-53, Taylor; this process describes obtaining the parent in each generator, not the daughter).
Claim 21: The method of claim 1, wherein the second stationary phase is selected to fix the decomplexed parent radioisotope while permitting the free complexing agent to pass through without binding, (See Abstract and See paragraph [0030], [0041], Fassbender; different complexing agents may pass through freely for different radioisotopes that are retained versus other complexing agents that complex with certain radioisotopes that are removed.).
Claim 22: The method of claim 1, wherein no purification step is performed between dissociating the complexes of the parent radioisotope and fixing the parent radioisotope on the second stationary phase, (See paragraph [0081] & [0083], Torgue, chromatography column 28 is the new generator/second stationary phase; and See paragraph [0023], [0060], Fassbender).
Claim 23: The method of claim 1, wherein the complexing agent is selected such that the parent isotope is eluted in complexed form, (See paragraph [0030], Fassbender), and the complex dissociates, (See paragraph [0023], [0060], Fassbender), upon acidification to a pH equal to or less than 1, (See paragraph [0030], Fassbender; Fassbender discloses adding acid to solution at a disclosed pH value of 1), resulting in the free form of the parent radionuclide, (See paragraph [0023], [0060], Fassbender).
Claim(s) 5, 14-16 & 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Torgue et al., (“Torgue”, US 2015/0170776), in view of Fassbender et al., (“Fassbender”, US 2015/0292061), in further view of Horwitz et al., (“Horwitz”, US 2003/0219366), in further view of Taylor et al., (“Taylor”, US 5,966,583), in further view of Drera, (US 10,636,536; The effective filing date of February 13, 2017 is relied upon).
Claims 5 & 14-16 are directed to a method for transferring a radioisotope, a method type invention group.
Regarding Claim 5, modified Torgue discloses the method of claim 4, wherein the first aqueous solution comprises ethylenediaminetetraacetic acid or a salt thereof and has a pH of 6 ± 0.5, (See paragraph [0030], Fassbender anticipates the claimed pH at 6).
Modified Torgue does not explicitly disclose using 25 mmol/L of ethylenediaminetetraacetic acid or a salt thereof.
Drera discloses a method of preparing radioisotopes, (See Abstract, Drera), which uses 25 mmol/L of ethylenediaminetetraacetic acid or a salt thereof, (See column 13, lines 7-29, Drera; Drera discloses a range up to 0.25 M EDTA, indicating a range of 0 to 0.25 M EDTA is used, into which 25 mmol/L, converted to 0.025 M falls).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Torgue by incorporating using 25 mmol/L of ethylenediaminetetraacetic acid [EDTA] or a salt thereof as in Drera because the selection of the concentration of EDTA is a result-effective variable in which the value can be optimized such that “the concentration…may be sufficient to realize desorption of one or more of progeny divalent cations” and “may be present in the…solution in an amount sufficient to facilitate desorption of divalent cations”, (See column 13, lines 20-25, Drera).
Regarding Claims 14-16, modified Horwitz discloses wherein the radioisotope is thorium, (See Table 1 and See paragraph [0061], Horwitz), but not specifically thorium-228, which is however contemplated, (See paragraph [0028], Horwitz).
Drera discloses wherein the radioisotope is thorium-228, (See column 3, lines 27-45, Drera).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Torgue by incorporating wherein the radioisotope is thorium-228 as in Drera because providing “therapeutically effective amounts of Pb-212…may thus be obtained”, (See Abstract, Drera), which “is provided to a medical entity (e.g. a hospital; a doctor; a drug manufacturer) for subsequent use”, (See column 3, lines 34-38, Drera), as desired in Torgue which “relates to a method of preparing lead (212) for medical use”, (See Abstract, Torgue).
Additional Disclosures Included:
Claim 15: The method of claim 14, wherein at least one of the first stationary phase and second stationary phase consist of particles comprising a polymer functionalised by molecules of a ligand of thorium-228, (See paragraph [0090], [0128], Horwitz; See paragraphs [0032] & [0034], Fassbender).
Claim 16: The method of claim 15, wherein the polymer is a polymethacrylate or a poly(styrene-co-divinylbenzene), and the ligand of thorium- 228 is N,N,N',N'-tetraoctyldiglycolamide, di(2-ethylhexyl)phosphoric acid, trioctylphosphine oxide or a mixture thereof, (See paragraph [0090], [0128], Horwitz; See paragraphs [0032] & [0034], Fassbender; See column 3, lines 27-45, Drera).
Regarding Claim 24, modified Horwitz discloses wherein the parent radioisotope is thorium, (See Table 1 and See paragraph [0061], Horwitz), but not specifically thorium-228, which is however contemplated, (See paragraph [0028], Horwitz).
Drera discloses wherein the parent radioisotope is thorium-228 and the method does not include fixing or recovering any decay product of the parent isotope, (See column 2, lines 33-67, column 3, lines 1-5, Drera).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Torgue by incorporating wherein the parent radioisotope is thorium-228 and the method does not include fixing or recovering any decay product of the parent isotope as in Drera because providing “therapeutically effective amounts of Pb-212…may thus be obtained”, (See Abstract, Drera), which “is provided to a medical entity (e.g. a hospital; a doctor; a drug manufacturer) for subsequent use”, (See column 3, lines 34-38, Drera), as desired in Torgue which “relates to a method of preparing lead (212) for medical use”, (See Abstract, Torgue).
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Torgue et al., (“Torgue”, US 2015/0170776), in view of Horwitz et al., (“Horwitz”, US 2003/0219366), in view of Fassbender et al., (“Fassbender”, US 2015/0292061). in further view of Taylor et al., (“Taylor”, US 5,966,583), in further view of Drera, (US 10,636,536; The effective filing date of February 13, 2017 is relied upon).
Claim 19 is directed to a method for transferring a radioisotope, a method type invention group.
Regarding Claim 19, Torgue discloses a method for obtaining a new generator from a used generator, the used generator comprising a radioactive isotope of thorium, radium, lead, bismuth or uranium, (See paragraph [0077]), which is fixed on a first stationary phase contained in a first chromatography column, (See paragraph [0078]), and the new generator comprising the radioisotope fixed on a second stationary phase contained in a second chromatography column, (See paragraph [0081] & [0083]), said method comprising: a) eluting the radioisotope from the used generator, wherein eluting comprising circulating in the first chromatography column, a first aqueous solution A1 to obtain an aqueous eluate, (See paragraph [0100], [0119] & [0120]), part of b) to obtain the radioisotope in a decomplexed form, (See paragraph [0120]); c) preparing the new generator by fixing the radioisotope present in the aqueous eluate obtained from step (b) on the second stationary phase contained in the second chromatography column, wherein fixing the radioisotope comprises circulating the aqueous eluate obtained from step (b) in the second chromatography column, the second stationary phase being suitable for fixing the radioisotope without fixing the impurity, (See paragraph [0123] & [0126]); and washing at least once with a second aqueous solution suitable for eluting the impurities in the free form without eluting the radioisotope from the second stationary phase, (See paragraph [0130] & [0131]); whereby the new generator is obtained, (See paragraph [0130] & [0131]).
Torgue does not explicitly disclose comprising a complexing agent complexing the radioisotope, where the aqueous eluate comprises complexes of the radioisotope, b) dissociating the complexes of the radioisotope present in the aqueous eluate to obtain the radioisotope in a decomplexed form and the complexing agent in a free form, wherein dissociating the complexes of the radioisotope comprises modifying the pH of the aqueous eluate, eluting the complexing agent in the free form.
Fassbender discloses a method, (See Abstract, See paragraph [0010], Fassbender), comprising a complexing agent complexing the radioisotope, where the aqueous eluate comprises complexes of the radioisotope, (See paragraph [0030], Fassbender), , b) dissociating the complexes of the radioisotope present in the aqueous eluate to obtain the radioisotope in a decomplexed form and the complexing agent in a free form, wherein dissociating the complexes of the radioisotope comprises modifying the pH of the aqueous eluate, eluting the complexing agent in the free form, (See paragraph [0023], [0060], Fassbender). Additional features of this disclosure are also included in the combination and claim mapped to in the Additional Disclosures section below.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of Torgue by incorporating comprising a complexing agent complexing the radioisotope, where the aqueous eluate comprises complexes of the radioisotope, b) dissociating the complexes of the radioisotope present in the aqueous eluate to obtain the radioisotope in a decomplexed form and the complexing agent in a free form, wherein dissociating the complexes of the radioisotope comprises modifying the pH of the aqueous eluate, eluting the complexing agent in the free form as in Fassbender because Torgue discusses “the radioactive decay chain of thorium 232….also…radium 224” and actinium (Ac), (See paragraph [0009], and Figure 1, Torgue), and Fassbender notes that “recovery of actinium involves separating actinium from thorium, which is present as Th(IV)” so “converting the soluble Th(IV) to soluble anionic complexes”, (See paragraph [0030], Fassbender), enables “the solution of anionic complexes of thorium(IV) [to be] then passed through a column” which “elute” while the radionuclides “retained…are those that did not form anionic complexes” such as “radium (II)”, (See paragraph [0031], Fassbender). Furthermore, providing additional washing allows the method “to remove additional thorium(IV) from the column” (See paragraph [0039] & [0041], Fassbender). Thus, Fassbender provides a “method for separating radium…from proton-irradiated targets of thorium [that is] desirable”, (See paragraph [0010], Fassbender), to obtain “radiological purity…such as radium”, (See paragraph [0029], Torgue).
Modified Torgue does not explicitly disclose that the used generator includes a first chromatography column.
Horwitz discloses a method using a first chromatography column, (See paragraph [0058], Horwitz). Additional features of this embodiment are included as part of the overall combination and claim mapped to in the Additional Disclosures section below.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Torgue by incorporating that the used generator comprises a first chromatography column as in Horwitz in order to obtain “an ideal generator…[that] should provide operational simplicity and convenience as well as reliable production of the theoretical yield of the daughter radionuclide having high chemical and radionuclidic purity”, (See paragraph [0034], Horwitz), while providing “better chromatographic operating performance”, (See paragraph [0041], Horwitz).
Modified Torgue does not explicitly disclose that the radioisotope is also fixed on the second stationary phase for the new generator, the new generator is a new radium-224 generator that comprises thorium-228, and the used generator is a used radium-224 generator that comprises thorium-228.
Taylor discloses the radioisotope is also fixed on the second stationary phase for the new generator, (See Abstract, and See column 2, lines 40-53).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Torgue by incorporating the radioisotope is also fixed on the second stationary phase for the new generator as in Taylor in order to recover the parent isotope “to provide a source of [parent isotope] for additional….generators”, (See Abstract, Taylor), such that it can “minimize what has previously been a radioactive waste stream and convert at least a portion of it into a useful product by recycling [parent isotope] activity from spent [parent/daughter radioisotope] generators”, (See column 2, lines 13-17, Taylor).
Drera discloses a method of preparing radioisotopes, (See Abstract, Drera), where the new generator is a new radium-224 generator that comprises thorium-228, and the used generator is a used radium-224 generator that comprises thorium-228, (See column 13, lines 30-62, Drera).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have modified the method of modified Torgue by incorporating where the new generator is a new radium-224 generator that comprises thorium-228, and the used generator is a used radium-224 generator that comprises thorium-228 as in Drera because “alpha particle emitting radioactive isotopes [such as these] may be beneficial for use in TAT [targeted alpha therapy]”, (See column 13, lines 30-32, Drera), when applied to “cancer therapy”, (See column 1, lines 43-51, Drera), as contemplated in Torgue, (See Abstract & [0004], Torgue).
Conclusion
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/JONATHAN M PEO/Primary Examiner, Art Unit 1779