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 .
DETAILED ACTION
Applicant’s submission dated 12/11/2024 is duly acknowledged.
Claims 1-21 are pending in this application, and have been examined on their merits in this action hereinafter.
Priority
This application is a DIV of 18/162,957 (filed on 02/01/2023, now PAT 12194265), which is a DIV of 14/893,115 (filed on 11/23/2015, now PAT 11596780), which is a 371 of PCT/US14/39806 (filed on 05/28/2014), which claims domestic benefit from US PRO 61/828,126 filed on 05/28/2013.
NOTE: 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
Claim Rejections - 35 USC § 103
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 1-21 (as presented) are rejected under 35 U.S.C. 103 as being unpatentable over Unger et al. (US 2003/0120204 A1; IDS dated 02/28/2025) taken with Oh et al (2008; NPL cited in IDS sated 02/28/2025) and Kritz et al (WO 2009/058147 A1; FOR cited as ref. [N] on PTO 892 form).
Claim 1 is directed to “A method for fabricating a microtank for delivering one or more gases in a controlled and sustained manner, the method comprising:
(a) providing or preparing one or more vessels, wherein the one or more vessels have a volume defined by at least one gas barrier and/or a means for mechanical support/confinement, wherein the volume of the one or more vessels is capable of being loaded with one or more gases at an atmospheric or a hyperbaric pressure and subsequently releasing the one or more gases in a controlled and sustained manner; and
(b) loading the one or more vessels with one or more gases.”
See also limitations of dependent claims 2-21 as currently presented.
NOTE: 112-(f) or 6ᵗʰ paragraph, means plus function issues in claim 1: It is noted that the recited optional feature of “a means for mechanical support/confinement” has been taken herein as per guidance provided in the instant disclosure of record (see parent specification 14/893,115, page 5, 4th and 5th paragraphs, for instance).
Unger et al (2003), while teaching oxygen delivery agents and uses thereof (see Title, Abstract, Example 1, and Claims), disclose a composition for oxygen delivery comprising stabilizing a material having a vesicular form (para. [0004]). Regarding instant claim 1, Unger also teaches vesicles [microtanks or vessels] as clathrate bound vesicles (para. [0027]), and defines a "clathrate" as referring to a solid, semi-porous or porous particle which may be associated with vesicles. In a preferred form, the clathrates may form a cage-like structure [vessels] containing cavities which comprise one or more vesicles bound to the clathrate, if desired. A stabilizing material may, if desired, be associated with the clathrate to promote the association of the vesicle with the clathrate (para. [0031]). Unger teaches the stabilizing materials that can comprise polymeric materials including polycaprolactone (PCL), polyvinyl alcohol (PVA), polylactic acid (PLA), polyglycoic acid, etc. (para. [0027], [0050], and [0071]). Unger further teaches (paragraph [0036]), that these stabilizing compounds or materials form or stabilize vesicles to prevent the escape of gases [gas barrier] from the vesicles until release is desired. Unger teaches that the gases may be completely entrapped [or loaded] in the material until release is desired. Unger teaches vesicles [or vessels] as microbubbles, microspheres, microballoons, microcapsules and voids (para. [0027]). Regarding claims 3 and 4, Unger teaches the clathrate bound vesicles (para. [0027]) are sized to have diameters of from about 2 mm to about 100 mm (para. [0140]). Regarding claims 19-21, Unger teaches oxygen delivery agents as a material comprising clathrate bound vesicles (para. [0027]) capable of carrying oxygen in vivo or in vitro (para. [0004] and [0022]).
Unger (regarding claim 18) also teaches gas filled bilayer vesicles [or microspheres or microballoons or closed-cell structure] as oxygen delivery agents (para. [0008], [0022], Fig. la, and Unger claim 52, for instance).
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The bilayer vesicle seen in Fig. la of Unger is comparable to a vesicle comprising a core and a shell configuration, which comprises multiple gas barriers.
Although, Unger does not explicitly exemplify the oxygen delivery microtank or vessels (vesicles or microspheres/scaffolds) comprising polymers as currently recited in instant claim 2, Unger teaches the stabilizing materials that include synthetic polymeric materials comprising polycaprolactone (PCL), polyvinyl alcohol (PVA), polylactic acid (PLA), polyglycoic acid, etc. (para. [0050], [0071]), which can be used to stabilize vesicles in order to prevent the escape of gases [i.e. confinement] from the vesicles until release is desired ([0036]). Unger also teaches that the gases may be completely entrapped [or loaded] in the material until release is desired, and defines a dispersion as a finely divided mixture of two or more phases (solid, liquid or gas) which can remain stable for extended periods of time (para. [0027], [0033]). Thus, to an artisan of ordinary skill in the art, it would have been clearly obvious to successfully incorporate and/or employ such stabilizing polymeric materials as already suggested by Unger.
Regarding claim 11, Unger does not explicitly disclose wherein the at least one gas barrier adapted to release the one or more gases from the volume of the one or more vessels with an outgassing profile having an exponentially decaying release of the one or more gases. However, Applicant's specification states: Fick's first law of diffusion states that gases will tend to diffuse from regions of higher partial pressures to regions of lower partial pressures. Hence, when initially placed in a hyperbaric chamber, gases will tend to permeate into the microtanks. Upon removal from the hyperbaric chamber, gases will tend to exit the microtanks, i.e., referred to herein as "outgassing." As a gas leaves a microtank, the driving force for subsequent gas release is reduced, typically resulting in an exponentially decaying release profile (see parent specification 14/893,115, p. 6, last full para, and p. 7, lines 2-8).
Unger teaches FIGS. 1A and 1C show cross-sections of hypothetical vesicles, where the spherical structure is stabilized on the inside by the partial pressures of the constituent gases as well as by the physical and chemical nature of the vesicle shell. On the outside, hydrostatic pressure and surface tension exert forces tending to cause the vesicle to collapse. The size of the vesicle will be a function of these competing internal and external forces. FIGS. 1B and 1D show cross-sections of semi-collapsed vesicles. This illustrates the effect of degassing the external aqueous environment, which causes outward diffusion of the trapped internal gases since the pressures inside and outside of the vesicle cannot reach equilibrium. However, when the internal component is a relatively water-insoluble gas, such as a perfluorocarbon, gas diffusion out will be minimized. The volume change of the vesicle, similarly, will be less than predicted from the ideal gas law, because of the intramolecular repulsion that the hydrophobic lipid tails exhibit in any potential compaction. Only the symmetry of the sphere will be appreciably altered. Eventually, as saturation of the external environment occurs, the vesicles will tend to return to spherical shapes (para. [0178]).
Thus, given the disclosure from Unger, it would be obvious to one of ordinary skill in the art (prior to the effective filing date of the claimed invention) that the vessels/vesicles as taught by Unger modify the release of the gases within. Therefore, one of ordinary skill in the art would have recognized that fact that the stabilizing compounds and vesicles taught by Unger would also demonstrate an exponentially decaying release of the one or more gases, as instantly claimed. In addition, Unger teaches that the release of the gases is activated by an application of a stimulus to the microtanks/vessels such as temperature or pressure (para. [0035], [0037], [0078]) which convert gaseous precursors to the required gas (para [0022]).
Regarding claims 15 and 16, Unger does not explicitly disclose the loading of the microtanks/vessels by “providing one or more-molecules capable of permeating the volume of the one or more vessels and modifying a gas freeing reaction contained therein to provide an outgassing profile having a modified release kinetics”; and “wherein the one or more molecules comprise water, and wherein the gas freeing reaction comprises a hydrolyzation reaction”. However, Unger teaches the inclusion of water in the vesicles (para. [0027]) and further teaches that hydrophilic interactions refers to molecules or portions of molecules which may substantially bind with, absorb and/or dissolve in water (para. [0046]). Claims 15 and 16 only require "one or more molecules" can comprise water that is capable of the function recited in the claims, and therefore, it would have been obvious to one of ordinary skill in the art that Unger teaches a material that further comprises one or more molecules that is capable of modifying gas release kinetics from the scaffold, such as water molecules.
However, Unger does not explicitly exemplify preparing microtanks (vessels or microspheres) for delivery of one or more gases- that comprises loading a “solid material” capable of decomposing in the gas” comprising calcium peroxide (see instant claims 8-9); and wherein one or more gases comprise nitric oxide or nitroglycerin (instant claim 10).
Oh et al (2009), while disclosing oxygen generating scaffolds for enhancing survival of engineered tissues (see Title, Abstract and Introduction on p. 757, in particular), teach calcium peroxide-based oxygen generating particles that were incorporated into 3-D scaffolds of Poly(dl-lactide-co-glycolide)(PLGA; see Abstract). Oh further teaches that the scaffold containing oxygen generating materials maintained elevated levels of oxygen when incubated under hypoxic conditions. These findings indicate that the use of oxygen generating biomaterials may allow for increased cell survivability while neovascularization is being established after implantation (Abstract). Oh also teaches to prepare paraffin particles as a porogen (i.e. a sacrificial porogen) for scaffold fabrication, paraffin beads were melted and immediately poured into a pre-warmed 0.5 wt% polyvinyl alcohol (PVA) aqueous solution while stirring. The paraffin-containing mixture was poured into excess cold water to solidify the paraffin. Paraffin particles were collected by microsieving this solution using standard testing sieves. To obtain PLGA/CPO blend scaffolds, PLGA was dissolved in dimethyl sulfoxide (DMSO). Calcium peroxide (CPO) powder was added at different concentrations into aliquots of the PLGA solution and these were mixed well. The CPO suspended PLGA solutions were then mixed with paraffin particles and the mixture was transferred to a silicone mold. The mold containing the PLGA/CPO/paraffin mixture was stored overnight and the frozen disc-shaped pre-scaffold was immersed in excess cold ethanol and then in hexane (paraffin removal step) for 2 days each. The PLGA/CPO scaffolds were stored under nitrogen until use to avoid PLGA degradation and CPO decomposition. During the 3-D scaffold fabrication, water which can react with CPO to produce oxygen was avoided to prevent premature oxygen generation (page 758, “Materials and methods”, section “2.2 Fabrication of PLGA/CPO scaffold”, in particular).
Although, Oh et al do not disclose the loading of nitric oxide or nitroglycerin in the microtanks/microspheres, such would have been obvious to an artisan of ordinary skill in the art because Kritz et al (2009) disclose drug-delivery compositions for sustained release comprising biodegradable polymeric particles or microspheres that can be loaded with therapeutic agents including gases such as nitric oxide or nitroglycerin (see Title, Abstract, [0023], [0040], [0093], [0096], Claims 1, 7-8, for instance), and wherein the microspheres have diameter of approximately 500 to 600 microns (see [00110], Example 1).
Thus, given the combined disclosure from Oh et al (when taken with Kritz et al), as discussed above, it would have been obvious to one of ordinary skill in the art to modify the method to prepare the vesicles (or microtanks or microspheres) of Unger to further include the calcium peroxide particles as taught by Oh et al, or include nitric oxide (NO) or nitroglycerin in the microspheres, as per need. One would be motivated to do so because Oh teaches the benefits such as elevated levels of oxygen, extended cell viability and increase cell survivability even under hypoxic conditions while incubating cells with calcium peroxide particles. Also, Kritz et al provide therapeutic benefits of such microspheres when administered in subjects in need thereof (see teachings from Kritz et al, [0097], claims 9-10, and discussion above), and therefore one would have a reasonable expectation of success because, like Unger (para. [0070]), Oh and Kritz both teach the use of the polymeric materials for making and using such therapeutic gas (including oxygen, NO)-generating microspheres or particles (i.e. microtanks/vessels) by incorporating calcium peroxide, or therapeutic agents such as nitroglycerin. Therefore, unless evidence/data provided on the record to contrary, the invention as generically claimed fails to distinguish itself over the combined teachings and/or suggestions from the cited prior art references as discussed above.
Thus, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention as currently claimed.
As per MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. In re American Academy of Science Tech Center, F.3d, 2004 WL 1067528 (Fed. Cir. May 13, 2004)(The USPTO uses a different standard for construing claims than that used by district courts; during examination the USPTO must give claims their broadest reasonable interpretation.). This means that the words of the claim must be given their plain meaning unless applicant has provided a clear definition in the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989).
Conclusion
NO claims are currently allowed.
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SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657
/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657
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