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) 7, 10, and 12 in the reply filed on 12/20/2023 is acknowledged.
Claims 7-11 were elected by the applicant in the reply filed on 6/22/2026.
Claims 7-11 are under examination.
Election/Restrictions
Applicant's election with traverse of Group II (claims 7-11) filed 6/22/2026 is acknowledged. The traversal is on the ground(s) that no burden of proof to support patentably distinctness with the restricted Groups is presented. The arguments are found unpersuasive because of the following reasons: (i) this application is a 371 of PCT/US2022/035922 and for applications filed under 371, PCT rules for lack of unity apply (ii) search burden is not required to show lack of unity. (iii) Further, the WO 2016/044846 indicates a lack of special technical feature, which supports that each of the groups of invention do not relate to a single inventive concept. Thus, the lack of unity is deemed proper.
Claims 1-6 and 12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group I, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 6/22/2026.
Applicant’s species selection of 2-(acetoxymethyl)-6-(4,5-diacetoxy-2-(acetoxyanethyl)-6-(4,5-diacetoxy-2-(acetoxymethyl)-6-(3-(4-(3-bromopropyl)-1H-1,2,3-tiazol-1-yl)propoxy)tetrahydro-2H-pyran-3-yl)oxy)tetrahydro-2H-pyran-3-yl)oxy)tetrahydro-2H-pyran-3,4,5-tiyl triacetate is acknowledged.
Drawings
The drawings are objected to because Fig 1A, B, C, D, Fig 2, and Fig 3 are blurry and difficult to read.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Interpretation
Claim 7 recites “contacting a compound as in claim 1 with hydrofluoric acid isotopically enriched with fluorine 18”. The examiner notes that the term “contacting” encompasses either addition of hydrofluoric acid enriched with fluorine-18 or generation in situ of hydrofluoric acid enriched with fluorine-18. Therefore, the examiner interprets any prior art that has hydrofluoric acid enriched with fluorine-18 to affect the chemical transformation as reading on this claim.
Claims 10 and 11 recite “polysaccharide or polysaccharide derivative isotopically enriched with fluorine 18”. The examiner notes that throughout the specification, the applicant means both the polysaccharide and polysaccharide derivatives are isotopically enriched with fluorine 18 for the methods of claims 10 and 11. Therefore, the examiner interprets this phrase to mean both the polysaccharide and polysaccharide derivative are labeled.
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.
Claims 7-8, 10-11 is/are rejected under 35 U.S.C. 103 as being obvious over Ning, X.; et al. (Ning, X.; et al., Angew. Chem. Int. Ed., 2014, 53, 14096-14101) and Goodman, M.; et al. (WO 2016/044846 A1) and Satter, M. R. et al. (Satter, M. R.; et al. Synthesis of the Fluorine-18 Labeled Inhalation Anesthetics, Appl. Radi. Isol. 1994, 45, 11, 1093-1100).
Ning, X.; et al. (hereafter referred to as Ning) is drawn to PET imaging of bacterial infections using fluorine-18-labelled polysaccharides (title; abstract). Ning teaches methods of synthesis for the fluorine-labelled polysaccharide (pg 14097, Scheme 1; pg 14096, col 2, para 4, lines 1-3 and pg 14096, col 1, para 1, lines 1-23), methods of targeting bacteria through maltodextrin transporters in bacteria (pg 14097, col 1, para 2, lines 1-3; pg 14097, col 2, para 3, lines 6-8); and methods of imaging (pg 14098, Fig 2-4; pg 14098, col 1, para 2, lines 11-12; pg 14099, col 2, para 1, lines 1-8; Fig 5-6).
As to claim 7, Ning teaches a method of generating a compound isotopically enriched with fluorine 18 (pg 14097, Scheme 1; pg 14096, col 2, para 4, lines 1-3 and pg 14096, col 1, para 1, lines 1-23) comprising contacting the compound described as
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(pg 14097, Scheme 1) and providing a compound isotopically enriched with fluorine 18 (pg 14097, Scheme 1, MH18F; pg 14097, col 1, para 1, lines 15-17).
Ning does not specifically teach maltotriose-based saccharide analogues.
Ning does not teach using hydrofluoric acid isotopically enriched with fluorine-18.
Goodman, M.; et al. (hereafter referred to as Goodman) is drawn to the use of saccharide analogs and agents for the diagnosis and therapy of bacterial infections (title; abstract). Goodman primarily teaches thiomaltose-based saccharide analogs labeled fluorescent (pg 2, lines 18-20;) or radiolabels (pg 2, lines 14-18) or antibiotic conjugates (pg 3, lines 1-28). These regions are connected through a variety of linkers (pg 51, claim 10) but 1,2,3-triazole linker groups (pg 23, Formula IG; Fig 15). In addition to thiomaltose-based saccharide analogs, Goodman also teaches maltose-based saccharide analogs (pg 4, lines 13-15; pg 39, lines 14-32; Fig 15, compound C) such as a fluorine-18 labeled maltotriose through 1,2,3-triazole linker group (Fig 15, compound C).
Regarding Maltotriose-based saccharide analogues, Goodman teaches fluorine-18 labeled maltotriose (Fig 15, compound C).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Ning to include a different saccharide-analogue such as maltotriose as taught by Goodman because the prior art contained a product which differed from the claimed product by the substitution of some component (the number of repeat units) with other components. The substituted components and their functions were known in the art. Therefore, a person of ordinary skill in the art could have substituted one known saccharide for another and the results of the substitution would have been predictable.
A person of ordinary skill in the art would have had a reasonable expectation of success in substituting the polysaccharides because the only difference between the saccharides are the number of repeat units, which means the chemistry of the labeling is unchanged. The skilled artisan would have been motivated to the shorter polysaccharide has the because polysaccharides are hydrolyzed by extracellular alpha-amylase into smaller saccharides. Reducing the number of sugars reduces the number of positions that can be hydrolyzed while still maintaining the necessary targeting for the bacteria.
Satter, R. M.; et al. (hereafter referred to as Satter) is drawn to the synthesis of labeling alkyl groups with fluorine-18 for PET studies in vivo (title; abstract; pg 1093, col 1, para 1, lines 20-23 and col 2, para 1, lines 1-2). Satter teaches a method in which isotopically enriched hydrofluoric acid is produced and then reacts with a compound to label it (pg 1097, col 1, para 4, lines 1-4). Satter teaches a variety of halogenated alkyls that can be labelled with fluorine (pg 1096, Table 1).
Regarding hydrofluoric acid, Satter teaches hydrofluoric acid contacting a compound for radiolabelling for PET studies (pg 1097, col 1, para 4, lines 1-4).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of the combined teachings of Ning and Goodman to include [18F]HF taught by Satter 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 contacting the precursor compound with fluorine-18 enriched hydrofluoric acid.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the source of the fluorine-18 isotope because Satter demonstrated the success of using a simple fluorine-18 source. The skilled artisan would have been motivated to use fluorine-18 enriched hydrofluoric acid because it is a simple source and generating fluorine-18 in situ is common for azeotropic drying processes of fluorine-18. Therefore, the product of the drying could also be used to affect the nucleophilic aliphatic substitution.
As to claim 8, Ning teaches contacting the compound isotopically enriched with fluorine-18 with a deacetylating agent such that alkanoyl groups are converted to hydroxy groups providing the polysaccharide enriched with fluorine-18 (pg 14097, Scheme 1, reaction 2; pg 14097, col 1, para 1, lines 10-13).
As to claim 10, Goodman teaches a method comprising administering a composition comprising a polysaccharide isotopically enriched with fluorine-18 to a subject (pg 3, lines 33-34 and pg 4, lines 1-4; pg 40, lines 15-18; claim 31).
As to claim 11, Goodman teaches detecting the emissions and creating an image indicating or highlighting the location of the compound containing the polysaccharide isotopically enriched with fluorine-18 in the subject (pg 4, lines 1-4; pg 40, lines 12-27; claim 32).
Claims 9 is/are rejected under 35 U.S.C. 103 as being obvious over Ning and Goodman and Satter in further view of Ren, B.; et al. (Ren, B.; et al. Zemplen transesterification: a name reaction that has misled us for 90 years. Green Chem., 2015, 17, 1390). The teachings of Goodman, Ning, and Satter as applied in the previous rejections are incorporated in this rejection.
As to claim 9, Ning teaches the deacetylating agent is a metal hydroxide in an aqueous environment (pg 14096, Scheme 1, reaction 2, step 2; pg 14097, col 1, para 1, lines 10-13).
Ning does not teach an aqueous ethanol solution.
Ren, B.; et al. (hereafter referred to as Ren) is drawn to a deacetylation reaction of carbohydrates (title; abstract; Table 1). Ren teaches that a variety of carbohydrate deacetylations (pg 1392, Table 2, entries 1-10) can be performed under a variety of basic conditions (pg 1391, Table 1, entries 1-11) and in either anhydrous alcohols (pg 1391, col 2, para 1, lines 4-7) or wet alcohol solutions (pg 1391, col 2, para 1, lines 7-10).
Regarding the aqueous ethanol solution, Ren teaches an aqueous alcohol solution. Ren teaches an alcohol with one carbon whereas the instant claimed alcohol has two carbons. Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In this case, the similarity between the chemical structures of the alcohol and their properties is sufficiently close that one of ordinary skill in the art would have been motivated to use the claimed compound in the reaction. See MPEP 2144.09(III).
It would have been prima facie obvious to a person of ordinary skill in the art before the
effective filing date to modify the combined teachings of the composition and method of Ning, Goodman, and Satter to include aqueous ethanol as taught by Ren 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 aqueous ethanol in the method.
A person of ordinary skill in the art would have had a reasonable expectation of success in using aqueous ethanol because Ren teaches aqueous ethanol can be used in deacetylation reactions generally. The skilled artisan would have been motivated to use aqueous ethanol because ensuring complete lack of water requires more effort and the prior art shows little effect on the deacetylation and the bases are more soluble in water.
Non-Statutory 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.
U.S. Patent No. 9,821,071
Claims 7-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 9,821,071 in view of Goodman, Ning, Satter, and Ren.
The instant claims are drawn to methods of generating a compound isotopically enriched with fluorine 18 by first reacting with hydrofluoric acid isotopically enriched with fluorine-18, deacetylating the protected hydroxy groups with a metal hydroxide, and administering to a subject in need thereof, imaging, and creating an image highlighting the compound location in the subject.
The conflicting claims of U.S. Patent No. 9,821,071 (hereafter referred to as ‘071) are drawn to a maltodextrin compound conjugated to a PET radionuclide which can be selected to be fluorine-18, where the maltodextrin has more than 2 glucose oligomers, and the composition may have 6 glucose oligomers attached to a propyl group attached to a 1,2,3-triazole linker group attached to a fluorine-18 terminally substituted propyl group.
The conflicting claims of ‘071 do not teach a method of deacetylating the protected hydroxy groups with a metal hydroxide and aqueous ethanol solution.
The conflicting claims of ‘071 do not teach methods of generating a compound isotopically enriched with fluorine-18 by reacting with hydrofluoric acid isotopically enriched with fluorine-18
The conflicting claims of ‘071 do not teach a method of administration and imaging a subject.
The conflicting claims of ‘071 do not teach a method of creating an image and highlighting the compound location in the subject.
However, these features are known in the art. As noted in the current rejections, the combined teachings of Goodman, Ning, Satter, and Ren render obvious instant claims 7-11.
Regarding a method of deacetylating the protected hydroxy groups with a metal hydroxide and aqueous ethanol, Ning teaches the deacetylating agent is a metal hydroxide in an aqueous environment (pg 14096, Scheme 1, reaction 2, step 2; pg 14097, col 1, para 1, lines 10-13).
Ning does not teach an aqueous ethanol solution.
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 to include a method as taught by Ning 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 method of producing the compound of conflicting claims ‘071.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the compound by a method of making the compound because the prior art of Ning discloses the compounds of the conflicting claims and shows a method by which it may be produced and the compound is has the same structure. The skilled artisan would have been motivated to proposing a method of making because the method of making a compound is essential for its production.
Regarding the aqueous ethanol solution, Ren teaches an aqueous alcohol solution. Ren teaches an alcohol with one carbon whereas the instant claimed alcohol has two carbons. Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In this case, the similarity between the chemical structures of the alcohol and their properties is sufficiently close that one of ordinary skill in the art would have been motivated to use the claimed compound in the reaction. See MPEP 2144.09(III).
It would have been prima facie obvious to a person of ordinary skill in the art before the
effective filing date to modify the teachings of the conflicting claims of ‘071 and the composition and method of Ning to include aqueous ethanol as taught by Ren 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 aqueous ethanol in the method.
A person of ordinary skill in the art would have had a reasonable expectation of success in using aqueous ethanol because Ren teaches aqueous ethanol can be used in deacetylation reactions generally in polysaccharides. The skilled artisan would have been motivated to use aqueous ethanol because ensuring complete lack of water requires more effort and the prior art shows little effect on the deacetylation and the bases are more soluble in water.
Regarding hydrofluoric acid, Satter teaches hydrofluoric acid contacting a compound for radiolabelling for PET studies (pg 1097, col 1, para 4, lines 1-4).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the method of the combined teachings of the conflicting claims and Ning and Ren to include [18F]HF taught by Satter 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 contacting the precursor compound with fluorine-18 enriched hydrofluoric acid.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the source of the fluorine-18 isotope of the conflicting claims because the prior art of Satter disclosed that fluorine-18 enriched hydrofluoric acid is a possible way to create fluorine-18 enriched compounds. The skilled artisan would have been motivated to use fluorine-18 enriched hydrofluoric acid because it is a simple source and generating fluorine-18 in situ is common for azeotropic drying processes of fluorine-18. Therefore, the product of the drying could also be used to affect the substitution.
Regarding a method of administration and imaging a subject, Goodman teaches a method comprising administering a composition comprising a polysaccharide isotopically enriched with fluorine-18 to a subject (pg 3, lines 33-34 and pg 4, lines 1-4; pg 40, lines 15-18; claim 31).
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 and composition and methods of Ning, Satter, and Ren to include administration and imaging of the composition as taught by Goodman 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 method of administering and imaging the composition.
A person of ordinary skill in the art would have had a reasonable expectation of success in modifying the method to have administration because the prior art of Goodman discloses that administration and imaging of these compositions is possible and an end use of the composition. The skilled artisan would have been motivated to modify the methods to include administration and imaging because the use increases value of a composition containing a radiolabeled compound if that compound can be administered and imaged.
Regarding a method of creating an image and highlighting the compound location in the subject, Goodman teaches detecting the emissions and creating an image indicating or highlighting the location of the compound containing the polysaccharide isotopically enriched with fluorine-18 in the subject (pg 4, lines 1-4; pg 40, lines 12-27; claim 32).
Conclusion
No claims allowed.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EVAN M LEWOCZKO/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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