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 .
Applicant’s arguments, filed 06/04/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 5 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 recites “wherein the ligand comprises at least any one of phosphate and phosphonate,” however, as claim 1 has been newly amended to recite that the ligands comprise a combination of AMP and ATP, it is unclear if claim 5 is attempting to define the AMP and ATP, or if the claim is intending the phosphate and phosphonate as further components in addition to the AMP and ATP. If intended to define the AMP and ATP, where AMP and ATP comprise phosphate, it is unclear how AMP and ATP can comprise phosphonate. For purposes of examination, the ligands AMP and ATP are interpreted as reading on the limitation of wherein the ligand comprises phosphate.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3-6, 10-13, 16-18, and 20, stand rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (J. Mater. Chem. B, 2014, 2, pp. 7132-7140), in view of Sternlicht et al (Jour. Amer. Chem. Soc., 1968, 90:25, pp. 7110-7118), as evidenced by Thomas et al (Ceramics Int., 2014, pp. 1-10).
Chen et al teach biodegradable mesoporous microspheres (i.e., a complex) comprising Ca2+, adenosine triphosphate (ATP) that is hydrolyzed (via heating) to adenosine diphosphate (ADP), adenosine monophosphate (AMP), phosphate, and adenosine, where the reaction between the calcium ions and phosphate ions self-assemble to form microspheres (fig. 3, pg 7135 1st col 2nd ¶). The microspheres are doped with europium (Eu3+) for in vitro/in vivo fluorescence imaging properties (abs). As evidenced by Thomas et al, europium doped compounds are used as fluorescent dyes (intro 3rd ¶, pg 2 1st col 3rd ¶). The Eu3+ doped microparticles were spherical with a diameter ranging from 200-300 nm (i.e., 0.2-0.3 microns) (3.1 2nd ¶, figs 1a and 1b). The microspheres were dispersed in phosphate buffered saline (PBS) (2.6), with a release over time measured up to 108 hours (4.5 days) (fig 7b).
Chen et al do not specifically teach wherein the ligand is AMP alone, which appears to be required for the needle shape to form (see pg 8 of the instant specification), the specific molar concentration ratio of AMP to ATP, nor the calcium ion and ligand ratio of 5:1 to 1:1.
Sternlicht et al teach metal ion-ligand complexes were known, and studies were conducted on the binding competition of metal ion (in this case Mn2+) to complexes comprising both AMP and ATP (abs, pg 7110 1st ¶). The studies were conducted using a 1:1 ratio of AMP to ATP, where the metal ion binds equally between the ATP and AMP (pg 7111 competition study 1st ¶ and pg 7112 2nd col). The ratio of metal to ligand in the complex are taught to be 1:1 or 1:2 (abs, pg 7111 1st col 4th ¶ and 5th ¶ full). Embodiments comprising only AMP and only ATP were also taught (pg 7113 1st col 1st ¶ and 2nd col 2nd ¶, pg 7112 1st col).
Regarding the combination of AMP and ATP with the molar ratios of claim 1, where Chen et al teaches metal ion-ligand complexes comprising AMP, etc., were known, and Sternlicht et al teaches complexes of metal ions with ATP, alone, or in combination with AMP at a molar ratio 1:1 were known, it would have been obvious to include a known combination of ligands for metal ion-ligand complexes, such as AMP and ATP, where it appears that adjusting the molar ratio of AMP to ATP would be obvious to a skilled artisan. Where complexes of metal ions comprising only AMP, only ATP, and the combination of AMP and ATP at a 1:1 ratio were known in the prior art, a 1:0 to 0:1 ratio would be obvious, thereby overlapping the claimed ranges. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding the reversibly self-assembly or self-disassembly of the complex of claim 1, where the self-assembled microparticles made obvious by the combination comprises ATP, ADP, AMP (ligands), and Ca2+ (calcium ion), the same components instantly claimed, the self-assembly or self-disassembly is inherent to the components of the complex, whether recognized or not. See MPEP 2112(II) and (III).
Regarding the shapes of a fibril and sphere of claim 1, where the claimed ranges are made obvious in the complex of Chen et al and Sternlicht et al above, it appears the resulting shapes are inherent to ligands in the complex and their amounts. See MPEP 2112(II) and (III).
Regarding the active agents of claim 1, Eu3+ doping is disclosed by Chen et al to have florescence imaging properties, which reads on a dye. Further, Eu3+ is evidenced by Thomas et al to be used as fluorescent dyes. As such, the active ingredient limitation of claim 1 is met.
Regarding claims 3 and 4, where the self-assembled complex made obvious above comprises AMP and ATP in the molar ratios instantly claimed, a calcium ion, and a dye, with spherical diameters ranging from 0.2-0.3 microns, the limitations are met. Further, it appears the resulting shapes are inherent to ligands in the complex and their amounts, which are obvious to adjust for the reasons discussed above. See MPEP 2112(II) and (III).
Regarding claim 5, the self-assembled complex made obvious by Chen et al and Sternlicht et al comprise ATP and AMP, which comprise phosphate, thereby reading on the instant claim limitation.
For the sake of argument, if phosphate was intended to be an additional component, Chen et al also teach the self-assembled complex comprises phosphate as an additional component of the complex, which would have been obvious to include.
Regarding claim 6, the self-assembled complex made obvious by Chen et al and Sternlicht et al further comprises ADP, as taught by Chen et al.
Regarding claim 10, where Chen et al discloses the bonding of calcium ions to phosphate ions of the ADP and AMP, and where the same components as instantly claimed are disclosed in the complex made obvious by Chen et al and Sternlicht et al, i.e., ligands, calcium ion, and active agent, the bonds that form between the adjacent ligands and the calcium ions and ligands are inherent to the components and their interactions with each other. See MPEP 2112(II) and (III).
Regarding claim 11, where the complexes formed are 1:1 or 1:2 complexes of metal ion to ligand as taught by Sternlicht et al, it would have been obvious to use a ratio of 1:1 as motivated by Sternlicht et al.
Regarding claims 12, 13, and 16-18, where the same components, i.e., ligands, calcium ions, and an active, as instantly claimed, and are formed through self-assembly and are added to PBS for release up to 4.5 days, it appears the self-disassembly is inherent to the components of the composition in the buffer solution. See MPEP 2112(II) and (III). Further, while the release rate is shown for docetaxel in fig 7b, it appears the Eu3+ doped complex disclosed by Fig. 3 above and throughout, without docetaxel, would release the active within the complex through the same disassembly process, where all components of the complex would be expected to release.
Regarding claim 20, where the self-assembled complex of claim 1 is made obvious above by Chen et al and Sternlicht et al and contains an active ingredient as instantly claimed, it appears it would be capable of being used for the intended use limitations of a in vivo/vitro substance delivery carrier, etc.
Response to Arguments
First, Applicants have amended claim 1 and asserts Chen et al and Sternlicht et al fail to disclose or suggest every claim limitation. Notably, Applicants have amended in AMP and ATP molar concentration ratios, as well as deleting adenosine from the list of claimed actives. Second, Applicants assert the broad range of the ratio between AMP and ATP taught by Sternlicht et al, i.e., either AMP alone, AMP:ATP 1:1, or ATP alone, encompass a very large number of possible ratios which cannot be considered as a prima facie case of obviousness based on overlapping ranges. Applicants assert that if a reference is so broad as to encompass a very large number of possible distinct combinations, this might present a situation analogous to the obviousness of a species when the prior art broadly discloses a genus. Applicants cite In re Baird for support. Further, Applicants assert Sternlicht et al is completely silent on varying the ratio of the AMP and ATP. Third, Applicants assert the skilled artisan would plainly understand that Chen et al and Sternlicht et al fail to disclose or suggest the newly amended claim limitations.
First, this argument is not persuasive. The combination of Chen et al and Sternlicht et al are discussed above. While Applicants have amended claim 1 to recite the molar ratios as well as deleting adenosine from the list of claimed actives, Sternlicht et al teach self-assembled metal ion complexes with AMP alone, ATP:ATP at a 1:1 molar ratio, and ATP alone were known, suggesting molar ratios from 1:0 to 0:1, and it would have been obvious for the skilled artisan select from within the known ratio, where the claimed ratio lies inside the ratio of the prior art. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). Further, while Applicants have deleted adenosine, Examiner notes that the previous rejection also recited a dye as an active agent, which has not been addressed by Applicants in the response. It appears that the dye taught by Chen et al reads the dye instantly claimed as an active agent.
Second, this argument is not persuasive. Where the prior art appears to tech a ratio of 1:0 to 0:1 as discussed above, which overlaps the claimed ratio ranges, a prima facie case of obviousness exists. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I). Simply asserting that the range is broad with a large number of possible ratios, does not mean that the ratios within the disclosed range are not obvious to select from. Applicants assert the broad range of ratios might present a situation analogous to a species in a broadly disclosed genus, however, selecting from disclosed ratios is not analogous to picking and choosing from species in a genus, where species within a genus can have different mechanisms of actions, etc. There appears to be no allegation of criticality or evidence of non-obviousness across the range suggested by the prior art. Lastly, Applicants assert that Sternlicht et al is silent on varying the ratio of AMP and ATP, however, Examiner notes that Sternlicht et al recites embodiments with AMP alone, ATP alone, ATP:AMP at a 1:1 molar ratio, which is a variation of ratios, thereby suggesting that the ratio of ATP and AMP can be varied.
Third, this argument is not persuasive. Examiner disagrees that the skilled artisan would understand that Chen et al and Sternlicht et al fail to teach the newly amended claim limitations, for the reasons discussed above and of record.
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 JOSHUA A ATKINSON whose telephone number is (571)270-0877. The examiner can normally be reached M-F: 9:00 AM - 5:00 PM + Flex.
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/JOSHUA A ATKINSON/Examiner, Art Unit 1612
/MARIANNE C SEIDEL/Primary Examiner, Art Unit 1600