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 .
Response to Arguments
Applicant's arguments filed February 26, 2026 have been fully considered but they are not persuasive. Amendments to the current set of claims have changed the scope of the claimed invention, resulting in additional new grounds of rejection.
On page 6 of the Remarks section, as indicated by the page number at the bottom of each page, Applicant discusses the status of the claims, and the previous objections and 112 rejections. The Examiner has withdrawn the previous objections and 112 rejections based on the amendments made here.
On pages 6-12, Applicant argues against the previous prior art rejection of independent Claim 1 regarding the 103 combination of primary reference Taylor et al., (“Taylor”, US 5,966,583), and secondary reference, Fassbender et al., (“Fassbender”, US 2015/0292061). On pages 6-8, Applicant summarizes the invention of Taylor, and compares and contrasts it to the present invention. Specifically, Applicant argues that Taylor uses a cation exchange resin that is washed with different mineral acid solutions, which the Examiner has related to the second/new generator. Applicant also argues that Taylor uses different mineral acids, and does not form citrate complexes and would not disclose dissociating citrate complexes by modifying pH prior to loading on the cation exchange resin/second stationary phase. In response, the Examiner notes that Taylor’s cation exchange resin acts in the same manner as the claimed generator since it has a stationary phase that fixes the component or radioisotope of interest. The Examiner also notes that the molecules of interest are bound to the resin, which is also used in chromatography columns for adsorption/desorption, which carries out the same action as chelation/de-chelation. Furthermore, the Examiner notes that Taylor is not relied upon to disclose the citrate complexing/decomplexing, but rather secondary reference Fassbender discloses this feature instead, (See paragraph [0023], [0039], [0060], [0069], Fassbender). The Examiner notes that this argument is considered piecemeal analysis, and is 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).
On pages 8-12, Applicant argues against the combination of Fassbender with Taylor. Applicant states that Fassbender discloses adjusting the pH of a citric acid solution so that thorium is converted into soluble anionic citrate complexes. Applicant assets that the claimed invention of Claim 1 requires that the radioisotope is first eluted in complexed form using a citric acid salt and then the citrate complexes are then dissociated by modifying the pH before the solution is loaded onto the second stationary phase. The Examiner notes that Fassbender additionally discloses dissociating the citrate complexes by modifying the pH, (See paragraph [0023], [0060], [0069], Fassbender). The Examiner takes the position that Fassbender discloses both complexing and dissociating the citrate and radioisotope as demonstrated above. Applicant continues to assert that Taylor only discloses mineral acid stripping and does not disclose citrate complexation chemistry, and that Fassbender does not form citate complexes and then dissociates them based on the acid and pH of the solution used. The Examiner notes that mineral acids used in Taylor are some of the same acids used in the claimed invention as well. The Examiner also notes that the cation exchange resin used in Taylor and/or Fassbender is also used in chromatography columns and/or generators. The Examiner notes that the instant Specification itself notes that the stationary phase material can include an organic material that uses ion exchange, (See paragraph [0051]). The Examiner further finds that Fassbender performs both complexing, (See paragraph [0030], Fassbender), and decomplexing or dissociating, (See paragraph [0023], [0039], [0060], [0069], Fassbender). For these reasons, the Examiner finds Applicant’s arguments here unpersuasive.
On pages 8-9, Applicant argues again that Taylor recovers and purifies strontium-82 using mineral acid stripping followed by ion-exchange purification. The Examiner notes that the mineral acids used here are the same kinds of acids claimed and/or further discussed in the claimed invention and instant Specification. Additionally, the Examiner reiterates that the stationary phase can be an organic material that uses ion exchange, (See paragraph [0051]), according to the instant Specification. Also, the Examiner notes that thorium is disclosed in Fassbender, not Taylor, so this is piecemeal analysis. For these reasons, the Examiner finds Applicant’s remarks here unpersuasive.
On pages 9-11, Applicant continues to reiterate the same arguments regarding the mineral acids, ion exchange resin, and citrate use of Taylor and the dissociation of the citrate complexes in Fassbender. Again, the Examiner responds in the same manner as above, in which Examiner notes that the mineral acids used here are the same kinds of acids claimed and/or further discussed in the claimed invention and instant Specification. Additionally, the Examiner reiterates that the stationary phase can be an organic material that uses ion exchange, (See paragraph [0051]), according to the instant Specification. The Examiner further finds that Fassbender performs both complexing, (See paragraph [0030], Fassbender), and decomplexing or dissociating, (See paragraph [0023], [0039], [0060], [0069], Fassbender). For these reasons, the Examiner finds Applicant’s arguments here unpersuasive.
On pages 10-11, Applicant argues that one of ordinary skill in the art would not have been motivated to combine Taylor and Fassbender because the “prior art provides no teaching that such a mechanism would predictably operate for the recited radionuclides, nor that the sequence of complex formation followed by intentional dissociation prior to loading would successfully regenerate a functional generator without intermediate purification”. The Examiner notes that Fassbender itself carries out the full range of events required in using radionuclides, complexing, (See paragraph [0030], Fassbender), and decomplexing them and regenerating the resin, (See paragraph [0023], [0039], [0060], [0069], Fassbender). As a result, the Examiner finds that Fassbender would demonstrate that it would predictably operate for the recited radioisotopes because it discloses doing so. The Examiner finds this argument unpersuasive.
Applicant also argues that the combination rejection relies upon impermissible hindsight. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). The Examiner finds this argument unpersuasive as a result.
The remainder of the remarks are moot as they do not present any more detailed arguments.
Priority
This application is a continuation-in-part of parent application SN 17/293,185, which has a EFD of 05/12/2021. However, the current application includes subject matter not discussed or claimed in the parent application, for example in independent Claim 1, “a citric acid salt”, thus the current application is given a EFD and examination date of August 15, 2023.
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, 2, 4-12 & 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Taylor et al., (“Taylor”, US 5,966,583), in view of Fassbender et al., (“Fassbender”, US 2015/0292061).
Regarding Claims 1, 2, 4-12 & 16, Taylor discloses a method for transferring a radioisotope which is fixed on a first stationary phase contained in a first chromatography column, (See column 2, lines 23-26), to a second stationary phase contained in a second chromatography column, (See column 2, lines 28-31, column 3, lines 63-65), to fix the radioisotope on the second stationary phase, (See column 2, lines 30-31), which comprises at least the following steps: a) eluting the radioisotope from the first stationary phase with an aqueous solution A1, (See column 3, lines 38-52), b) modifying a pH of the aqueous solution A2, whereby an aqueous solution A3 is obtained; c) loading the second stationary phase with the aqueous solution A3, (See column 3, lines 60-67, colun 4, lines 1-12); and d) washing at least once the second stationary phase with an aqueous solution A4, (See column 4, lines 17-21).
Taylor does not disclose the radioisotope being a radioactive isotope of thorium, radium, lead, bismuth or uranium, step a) eluting with the aqueous solution containing a citric acid salt as an agent complexing the radioisotope, whereby an aqueous solution A2 which comprises citrate complexes of the radioisotope is obtained, step b) dissociating the citrate complexes of the radioisotope present in the aqueous solution A2 by modifying said pH.
Fassbender discloses the radioisotope being a radioactive isotope of thorium, radium, lead, bismuth or uranium, (See paragraph [0011] & [0004], Fassbender), step a) eluting with the aqueous solution containing a citric acid salt as an agent complexing the radioisotope, (See paragraph [0030], Fassbender), whereby an aqueous solution A2 which comprises citrate complexes of the radioisotope is obtained, (See paragraph [0030], Fassbender), step b) dissociating the citrate complexes of the radioisotope present in the aqueous solution A2 by modifying said pH, (See paragraph [0023], [0060], [0069], Fassbender).
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 Taylor by incorporating the radioisotope being a radioactive isotope of thorium, radium, lead, bismuth or uranium, step a) eluting with the aqueous solution containing a citric acid salt as an agent complexing the radioisotope, whereby an aqueous solution A2 which comprises citrate complexes of the radioisotope is obtained, step b) dissociating the citrate complexes of the radioisotope present in the aqueous solution A2 by modifying said pH as in Fassbender because in Fassbender, “other cationic radionuclides elute through the column of resin”, (See paragraph [0023], Fassbender), such as strontium, (See paragraph [0040], Fassbender), overlapping with Taylor, (See Abstract, Taylor), in which “methods for separating…other radionuclide fission products…from proton-irradiated targets of thorium remain desirable”, (See paragraph [0010], Fassbender), to use in “medical applications”, (See paragraph [0004], Fassbender), like Taylor, (See column 1, lines 16-21, Taylor).
Additional Disclosures Included:
Claim 2: The method of claim 1, wherein the citric acid salt is an alkali metal citrate, an alkaline earth metal citrate or an ammonium citrate, (See paragraph [0039], Fassbender).
Claim 4: The method of claim 1, wherein the aqueous solution A1 comprises from 0.1 mol/L to 1 mol/L of an ammonium citrate, (See paragraph [0069]; 0.5 M or mol/L; or See paragraph [0030], Fassbender), and has a pH of at least 8, (See paragraph [0030], Fassbender).
Claim 5: The method of claim 1, wherein the modifiying of the pH recited in step b) of the aqueous solution A2 is an acidification to bring the pH of the aqueous solution A2 to a value of 1 or less, (See paragraph [0030], Fassbender discloses adding acid at a pH of 1).
Claim 6: The method of claim 5, wherein the acidification of the aqueous solution A2 comprises an addition of an acid to the aqueous solution A2, (See column 3, lines 38-42, Taylor; or See paragraph [0030], Fassbender).
Claim 7: The method of claim 6, wherein the acid is nitric acid, (See column 3, lines 38-42, Taylor; or See paragraph [0023], Fassbender).
Claim 8: The method of claim 5, wherein the acidification of the aqueous solution A2 comprises at least one washing of the first stationary phase with an acidic aqueous solution and an addition of all or part of the aqueous solution issued from the washing to the aqueous solution A2, (See column 3, lines 38-42, and lines 48-54; multiple passthroughs of acid via elutions are performed).
Claim 9: The method of claim 8, wherein the acidic aqueous solution comprises from 0.01 mol/L to 4 mol/L of nitric acid, (See column 3, lines 43-45, Taylor; anticipates claimed range from 0.5 to 1.5).
Claim 10: The method of claim 1, wherein the aqueous solution A4 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 column 3, lines 43-45, Taylor; anticipates claimed range from 0.5 to 1.5).
Claim 11: 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 column 3, lines 1-3; first generator has hydrous tin oxide; See column 4, lines 1-7, second column has acid resin).
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 different, (See column 3, lines 1-11; first generator has hydrous tin oxide; second generator also has hydrous tin oxide when the generator is recycled).
Claim 16: The method of claim 1, wherein no purification step is performed between dissociating the complexes of the radioisotope and fixing the radioisotope in decomplexed form on the second stationary phase, (See paragraph [0023], [0060], Fassbender; no purification step is disclosed/mentioned).
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Taylor et al., (“Taylor”, US 5,966,583), in view of Fassbender et al., (“Fassbender”, US 2015/0292061), in further view of Matsushita et al., (“Matsushita”, US 4,556,538).
Regarding Claim 3, modified Taylor discloses the method of claim 2, but does not explicitly disclose wherein the citric acid salt is diammonium citrate.
Matsushita discloses wherein the citric acid salt is diammonium citrate, (See column 6, lines 19-25, Matsushita).
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 Taylor by incorporating wherein the citric acid salt is diammonium citrate as in Matsushita in order to provide “eluting solutions capable of migrating a plurality of micro-concentration components present in a sample aqueous solution” and using “an eluting solution having a high affinity with an ion exchange gel”, (See column 3, lines 67-68, column 4, lines 1-11, Matsushita).
Claim(s) 13-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Taylor et al., (“Taylor”, US 5,966,583), in view of Fassbender et al., (“Fassbender”, US 2015/0292061), in further view of Drera, (US 10,636,536; The effective filing date of February 13, 2017 is relied upon).
Regarding Claims 13-15, modified Taylor discloses the method of claim 1, but does not disclose wherein the radioisotope is thorium-228. Modified Taylor however contemplates the use of thorium, (See paragraph [0011] & [0004], Fassbender).
Drera discloses the radioisotope being thorium-228, (See column 3, lines 34-38, column 8, lines 17-30, 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 Taylor by incorporating wherein the radioisotope is thorium-228 as in Drera because providing “therapeutically effective amounts…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).
Additional Disclosures Included:
Claim 14: The method of claim 13, wherein at least one of the first stationary phase and second stationary phase consists of particles comprising a polymer functionalised by molecules of a ligand of thorium-228, (See paragraph [0032], [0034], Fassbender, See column 3, lines 27-45, Drera).
Claim 15: The method of claim 14, 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 [0032], [0034], Fassbender, See column 3, lines 27-45, Drera).
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Taylor et al., (“Taylor”, US 5,966,583), in view of Fassbender et al., (“Fassbender”, US 2015/0292061), in further view of Drera, (US 10,636,536; The effective filing date of February 13, 2017 is relied upon).
Regarding Claim 17, Taylor discloses a method for transferring a radioisotope which is fixed on a first stationary phase contained in a first chromatography column, (See column 2, lines 23-26), to a second stationary phase contained in a second chromatography column, (See column 2, lines 28-31, column 3, lines 63-65), to fix the radioisotope on the second stationary phase, (See column 2, lines 30-31), which comprises at least the following steps: a) eluting the radioisotope from the first stationary phase with an aqueous solution A1, (See column 3, lines 38-52), b) modifying a pH of the aqueous solution A2, whereby an aqueous solution A3 is obtained; c) loading the second stationary phase with the aqueous solution A3, (See column 3, lines 60-67, column 4, lines 1-12); and d) washing at least once the second stationary phase with an aqueous solution A4, (See column 4, lines 17-21).
Taylor does not disclose the radioisotope being thorium-228, step a) eluting with the aqueous solution A1 containing a citric acid salt as an agent complexing the radioisotope, whereby an aqueous solution A2 which comprises citrate complexes of the radioisotope is obtained, step b) dissociating the citrate complexes of the radioisotope present in the aqueous solution A2 by modifying said pH, whereby the aqueous solution comprising the radioisotope is obtained.
Fassbender discloses the radioisotope being a radioactive isotope of thorium, (See paragraph [0011] & [0004], Fassbender), step a) eluting with the aqueous solution containing a citric acid salt as an agent complexing the radioisotope, (See paragraph [0030], Fassbender), whereby an aqueous solution A2 which comprises citrate complexes of the radioisotope is obtained, (See paragraph [0030], Fassbender), step b) dissociating the citrate complexes of the radioisotope present in the aqueous solution A2 by modifying said pH, whereby the aqueous solution comprising the radioisotope is obtained (See paragraph [0023], [0060], [0069], Fassbender).
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 Taylor by incorporating the radioisotope being a radioactive isotope of thorium, step a) eluting with the aqueous solution containing a citric acid salt as an agent complexing the radioisotope, whereby an aqueous solution A2 which comprises citrate complexes of the radioisotope is obtained, step b) dissociating the citrate complexes of the radioisotope present in the aqueous solution A2 by modifying said pH whereby the aqueous solution comprising the radioisotope is obtained as in Fassbender because in Fassbender, “other cationic radionuclides elute through the column of resin”, (See paragraph [0023], Fassbender), such as strontium, (See paragraph [0040], Fassbender), overlapping with Taylor, (See Abstract, Taylor), in which “methods for separating…other radionuclide fission products…from proton-irradiated targets of thorium remain desirable”, (See paragraph [0010], Fassbender), to use in “medical applications”, (See paragraph [0004], Fassbender), like Taylor, (See column 1, lines 16-21, Taylor).
Modified Taylor does not disclose the radioisotope being thorium-228.
Drera discloses the radioisotope being thorium-228, (See column 3, lines 34-38, column 8, lines 17-30, 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 Taylor by incorporating wherein the radioisotope is thorium-228 as in Drera because providing “therapeutically effective amounts…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).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 JONATHAN M PEO whose telephone number is (571)272-9891. The examiner can normally be reached M-F, 9AM-5PM.
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/JONATHAN M PEO/Primary Examiner, Art Unit 1779