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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on June 29, 2026 is acknowledged.
Specification
The abstract of the disclosure is objected to because it is too short in length (32 words). Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally be limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Appropriate correction is required.
Claim Rejections - 35 USC § 112 Indefiniteness
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.
Claims 14, 15, 24, 30, 55, and 64 are 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.
Claims 14 and 15 recite the limitation “the UV absorbent nanoscale material.” The claims lack an antecedent basis for this limitation as “an UV absorbent nanoscale material” is not previously recited in the claims. It is suggested that claim 11 be amended to “an ultraviolet (UV) absorbent small molecule or nanoscale material” to obviate this rejection.
Claim 24 recites the limitation “the hydrogel.” The claim lacks an antecedent basis for this limitation as “a hydrogel” is not previously recited in the claims. Note that “a hydrogel matrix” is previously recited in the claims. It is suggested that claim 24 be amended to “the hydrogel matrix” to obviate this rejection.
Claims 30, 55, and 64 recites the limitation “the engineered bacteria.” The claims lack an antecedent basis for this limitation as “engineered bacteria” is not previously recited in the claims. Note that “engineered bacterial biosensor” is previously recited in the claims. It is suggested that claims be amended to “the engineered bacterial biosensor” to obviate this rejection.
Clarification and/or amendment is required.
Claims 43, 48, and 51 are 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.
Claims 43 and 48 depend from claim 2, which has been canceled. A dependent claim that refers to a canceled claim is indefinite because it incorporates by reference limitations from a non-existent claim, rendering the scope of dependent claim unclear and incomplete.
The dependent claims fall therewith.
Clarification and/or amendment is required.
Claim 51 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 51 recites “human microbial peptides (AMPs)” and the recitation renders the scope of the claimed subject matter ambiguous and unclear to one of ordinary skill in the art. The acronym “AMPs” is universally recognized in the relevant art to denote “antimicrobial peptides.” However, the phrase “human microbial peptides” is not a standard or recognized term of art, and the specification provides no special definition or lexicography for this term to clarify its intended meaning. “Microbial peptides” (peptides originating form microorganisms” and “antimicrobial peptides” (peptides that exhibit activity against microbes, such as host-defense peptides produced by humans) represent fundamentally distinct biological concepts with different structural and functional properties. Because of the conflict between the written text and the defined acronym, coupled with the lack of clarification in the specification, it is unclear whether the claimed PhoPQ system is intended to detect peptides generated by human-associated microbes or human host-derived antimicrobial peptides. Accordingly, a person having ordinary skill in the art must speculate as to the true scope and boundary of the claim, rendering claim 51 indefinite.
Clarification and/or amendment is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3, 18, 27, 30, 55, and 64 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sayler et al. (US 2003 0108980; cited on IDS filed September 04, 2024).
Regarding claims 1 and 3, Sayler discloses a device comprising a genetically modified (engineered) bacterium producing a bioluminescent protein in the presence of divalent mercury (biosensor) (claim 14). Sayler discloses that the bacterium can be encapsulated in a matrix such as alginate (hydrogel) (claim 15).
Regarding claim 18, Sayler discloses that the matrix can comprise polyacrylamide (claim 15).
Regarding claims 27 and 30, Sayler discloses that the bacterium can be encapsulated in a matrix such as alginate (hydrogel) (claim 15). It can be expected that the device comprises an inner core and outer shell structure, and that the inner core comprises the genetically modified bacterium.
Regarding claim 55, Sayler discloses that the genetically modified bacterium can be Escherichia coli (E. coli)(claim 23).
Regarding claim 64, Sayler discloses that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte (FIG. 1).
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, 3-8, 18, 27, 30, 55, and 64 are rejected under 35 U.S.C. 103 as being unpatentable over Sayler et al. (US 2003 0108980; cited on IDS filed September 04, 2024) in view of Degen et al. (Journal of Physics: Condensed Matter, 2015; cited on PTO-892).
As discussed above, regarding claims 1 and 3, Sayler discloses a device comprising a genetically modified (engineered) bacterium producing a bioluminescent protein in the presence of divalent mercury (biosensor) (claim 14). Sayler discloses that the bacterium can be encapsulated in a matrix such as alginate (hydrogel) (claim 15). Regarding claim 18, Sayler discloses that the matrix can comprise polyacrylamide (claim 15). Regarding claims 27 and 30, Sayler discloses that the bacterium can be encapsulated in a matrix such as alginate (hydrogel) (claim 15). It can be expected that the device comprises an inner core and outer shell structure, and that the inner core comprises the engineered bacterium. Regarding claim 55, Sayler discloses that the genetically modified bacterium can be E. coli (claim 23). Regarding claim 64, Sayler discloses that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte (FIG. 1).
Sayler does not disclose that the alginate is present at a concentration of 0.1 -10 weight percent (instant claim 4). Sayler does not disclose that the hydrogel matrix is paramagnetic and that the hydrogel matrix further comprises a magnetic small material or nanoscale material such as iron oxide (instant claims 5-8).
Degen discloses magneto-responsive alginate capsules (title). Degen discloses that 2% wt concentration of alginate can be used for preparing the alginate capsules (page 4, column 1, ¶ 4). Degen discloses that different kinds of magnetic nanoparticles (mNPs) such as superparamagnetic iron oxide can be incorporated in different locations of the capsule such as in the matrix of the beads, in the core, or inside the shell of the capsules (page 2, column 1, ¶ 4; page 9, column 2, ¶ 2). Degen discloses that these magneto-responsive systems have a wide range of potential applications such as drug delivery systems, especially the capsules with mNPs solely inside the shell can be interesting for pharmaceutical application because no magnetic material will be released by a capsule break (abstract; page 10, column 1, ¶ 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Sayler by using a 2 wt% concentration of alginate and incorporating paramagnetic iron oxide nanoparticles into the hydrogel matrix to expand the applications of the device. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Degen teaches that a 2 wt% concentration of alginate can be used for preparing capsules, and that paramagnetic nanoparticles such as iron oxide can be incorporated into the alginate matrix for pharmaceutical applications. Further, a person of ordinary skill in the art would have been motivated to optimize the amount of alginate according to the specific requirements of the application. The concentration of alginate is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of the alginate for achieving the desired characteristics of the device as the concentration of alginate critically determines the characteristics such as size, shape, stability, permeability, and encapsulation efficiency. A person of ordinary skill in the art would have been motivated to combine iron oxide nanoparticles with alginate matrix in order to create a multifunctional composite for biomedical applications such magnetic resonance imaging (MRI) and magnetic targeting and delivery. Accordingly, applying the teachings of Degen to the device of Sayler constitutes no more than the predictable use of prior art elements according to their established functions and therefore renders instant claims obvious.
Claims 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Sayler et al. (US 2003 0108980; cited on IDS filed September 04, 2024) in view Chawarai et al. (US 2016 0128944; cited on PTO-892), Wang et al. (RSC advances, 2013; cited on PTO-892), and Guo et al. (BioResources, 2020; cited on PTO-892).
Sayler is discussed above.
Sayler does not disclose that the hydrogel matrix further comprises an ultraviolet (UV) absorbent small molecule such as photoabsorber or tartrazine; or nanoscale material such as natural polymer or titanium oxide.
Chawarai discloses a particle comprising an active agent, a core and a coating layer (claim 94). Chawarai discloses that the active agent can be present in the core or the coating layer and that the active agent can be UV light absorbing agents such as benzophenone (photoabsorber) (claim 96; claim 100; ¶ 182; ¶ 233). Chawarai discloses that the active agent can be tartrazine or titanium oxide (¶ 21; ¶ 71).
Wang discloses polypropylene (PP)/Mg3Al–tartrazine layered double hydroxide (LDH) nanocomposites for enhanced UV absorption (abstract). Wang discloses that tartrazine can be an excellent UV absorber (page 26017, column 2, ¶ 3).
Guo discloses that lignin-TiO2 (titanium dioxide)@NFC (nanofibrillated cellulose) composites (nanoparticles) shows a good UV light absorption (abstract). Guo discloses that TiO2 have an ability to absorb a wide range of UV radiation, and that lignin (natural polymer) can have a property of UV-absorption (Page 7374, ¶ 2; page 7375, ¶ 5).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Sayler by incorporating a UV absorbent small molecule or nanoscale material such as benzophenone, tartrazine, titanium oxide, or lignin nanoparticles to improve the device by preventing UV damage. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Chawarai teaches that the device can comprise UV light absorbing agents like benzophenone; Wang teaches tartrazine can be used as a UV absorber; and Guo teaches that TiO2 and lignin can be used as UV absorbers. Further, a person of ordinary skill in the art would have been motivated to utilize such a UV absorber for the device in order to protect the living bacterial biosensors from UV damage, prevent the hydrogel matrix from degrading, and reduce optical noise and signal interference for accurate sensor readouts. Accordingly, applying the teachings of Chawarai, Wang, and Guo to the device of Sayler constitutes no more than the predictable use of prior art elements according to their established functions and therefore renders instant claims 11-15 obvious.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Sayler et al. (US 2003 0108980; cited on IDS filed September 04, 2024) in view of Ochi et al. (Advanced Powder Technology, 2014; cited on PTO-892).
Sayler is discussed above.
Sayler does not disclose that the hydrogel comprises tetramethylethylenediamine (TEMED).
Ochi discloses a method of preparing hydrogel capsules (page 605, column 1, ¶ 5). Ochi discloses that the hydrogel capsule can comprise TEMED as a polymerization accelerator (page 605, column 1, ¶ 5).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use TEMED for preparing the polymerized hydrogels of Sayler more efficiently. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ochi teaches that TEMED can be used as a polymerization accelerator when preparing hydrogel capsules. Further, a person of ordinary skill in the art would have been motivated to utilize TEMED to drive the free-radical crosslinking of monomers such as acrylamide into a solid hydrogel shell, allowing rapid, controlled polymerization at room temperature for encapsulating drugs or cells without heat damage. Accordingly, applying the teachings of Ochi to the device of Sayler constitutes no more than the predictable use of prior art elements according to their established functions and therefore renders instant claim 24 obvious.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Sayler et al. (US 2003 0108980; cited on IDS filed September 04, 2024) in view of Ma et al. (US 2014 0271843; cited on PTO-892).
Sayler is discussed above.
Sayler does not disclose that the outer shell is semi-permeable.
Ma discloses hydrogel capsules encapsulating cells for therapeutical applications (abstract). Ma discloses the fabrication of core-shell capsules with the shell fluid consists of a cell-free alginate solution, while the core fluid contains therapeutic cells (¶ 99). Ma discloses that the surface of the microcapsules can be crosslinked with polyamino acids to form a semi-permeable membrane (¶ 102).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Sayler by making the outer shell semi-permeable. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ma teaches that the outer shell can be semi-permeable. Further, a person of ordinary skill in the art would have been motivated to utilize semi-permeable outer shell in order to allow selective permeability for nutrient and target analytes. Accordingly, applying the teachings of Ma to the device of Sayler constitutes no more than the predictable use of prior art elements according to their established functions and therefore renders instant claim 31 obvious.
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.
Claims 1, 3-8, 11-15, 18, 24, 27, 30, 31, 55, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. US 9,555,007 (cited on PTO-892) in view of Sayler et al. (US 2003 0108980; cited on IDS filed September 04, 2024), Degen et al. (Journal of Physics: Condensed Matter, 2015; cited on PTO-892), Chawarai et al. (US 2016 0128944; cited on PTO-892), Wang et al. (RSC advances, 2013; cited on PTO-892), Guo et al. (BioResources, 2020; cited on PTO-892), Ochi et al. (Advanced Powder Technology, 2014; cited on PTO-892), and Ma et al. (US 2014 0271843; cited on PTO-892).
Regarding claims 1, 27, and 30, claim 1 of the ‘007 recites hydrogel capsules encapsulating cells. Claim 1 of the ‘007 recites the hydrogel capsules can have core-shell structures and the core can comprise cells. Claims of the ‘007 do not recite engineered bacterial biosensor. As discussed above, Sayler discloses a device comprising a genetically modified (engineered) bacterium producing a bioluminescent protein in the presence of divalent mercury (biosensor) (claim 14). Sayler discloses that the bacterium can be encapsulated in a matrix such as alginate (hydrogel) (claim 15). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogen capsules of the ‘007 by replacing the cells with engineered bacterial biosensor for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches engineered bacterial biosensor can be encapsulated in a hydrogel matrix. Further, a person of ordinary skill in the art would have been motivated to utilize the engineered bacterial biosensor in order to expand the applications of the capsules of the ’486.
Regarding claims 3, claim 6 of the ‘007 recites the polymer can comprise polysaccharides such as alginate.
Regarding claim 4, claims of the ‘007 do not recite that the alginate is present at a concentration of 0.1- 10 weight percent. As discussed above, Degen discloses magneto-responsive alginate capsules (title). Degen discloses that 2% wt concentration of alginate can be used for preparing the alginate capsules (page 4, column 1, ¶ 4). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘007 by using a 2 wt% concentration of alginate. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Degen teaches that a 2 wt% concentration of alginate can be used for preparing capsules. Further, a person of ordinary skill in the art would have been motivated to optimize the amount of alginate according to the specific requirements of the application. The concentration of alginate is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of the alginate for achieving the desired characteristics of the capsules as the concentration of alginate critically determines the characteristics such as size, shape, stability, permeability, and encapsulation efficiency.
Regarding claims 5-8, claims of the ‘007 do not recite that the hydrogel matrix is paramagnetic and that the hydrogel matrix further comprises a magnetic small material or nanoscale material such as iron oxide. As discussed above, Degen discloses that the hydrogel matrix is paramagnetic and that the hydrogel matrix further comprises a magnetic small material or nanoscale material such as iron oxide (instant claims 5-8). As discussed above, Degen discloses that different kinds of magnetic nanoparticles (mNPs) such as superparamagnetic iron oxide can be incorporated in different locations of the capsule such as in the matrix of the beads, in the core, or inside the shell of the capsules (page 2, column 1, ¶ 4; page 9, column 2, ¶ 2). Degen discloses that these magneto-responsive systems have a wide range of potential applications such as drug delivery systems, especially the capsules with mNPs solely inside the shell can be interesting for pharmaceutical application because no magnetic material will be released by a capsule break (abstract; page 10, column 1, ¶ 1). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘007 by incorporating paramagnetic iron oxide nanoparticles into the hydrogel matrix to expand the applications of the device. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Degen teaches that paramagnetic nanoparticles such as iron oxide can be incorporated into the alginate matrix for pharmaceutical applications. Further, a person of ordinary skill in the art would have been motivated to combine iron oxide nanoparticles with alginate matrix in order to create a multifunctional composite for biomedical applications such magnetic resonance imaging (MRI) and magnetic targeting and delivery.
Regarding claims 11-15, claims of the ‘007 do not recite that the hydrogel matrix further comprises an ultraviolet (UV) absorbent small molecule such as photoabsorber or tartrazine; or nanoscale material such as natural polymer or titanium oxide. As discussed above, Chawarai discloses a particle comprising an active agent, a core and a coating layer (claim 94). Chawarai discloses that the active agent can be present in the core or the coating layer and that the active agent can be UV light absorbing agents such as benzophenone (photoabsorber) (claim 96; claim 100; ¶ 182; ¶ 233). Chawarai discloses that the active agent can be tartrazine or titanium oxide (¶ 21; ¶ 71). As discussed above, Wang discloses polypropylene (PP)/Mg3Al–tartrazine layered double hydroxide (LDH) nanocomposites for enhanced UV absorption (abstract). Wang discloses that tartrazine can be an excellent UV absorber (page 26017, column 2, ¶ 3). As discussed above, Guo discloses that lignin-TiO2 (titanium dioxide)@NFC (nanofibrillated cellulose) composites (nanoparticles) shows a good UV light absorption (abstract). Guo discloses that TiO2 have an ability to absorb a wide range of UV radiation, and that lignin (natural polymer) can have a property of UV-absorption (Page 7374, ¶ 2; page 7375, ¶ 5). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘007 by incorporating a UV absorbent small molecule or nanoscale material such as benzophenone, tartrazine, titanium oxide, or lignin nanoparticles into the hydrogel matrix to improve the capsules by preventing UV damage. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Chawarai teaches that the capsules can comprise UV light absorbing agents like benzophenone; Wang teaches tartrazine can be used as a UV absorber; and Guo teaches that TiO2 and lignin can be used as UV absorbers. Further, a person of ordinary skill in the art would have been motivated to utilize such a UV absorber for the capsules in order to protect the living bacterial biosensors from UV damage, prevent the hydrogel matrix from degrading, and reduce optical noise and signal interference for accurate sensor readouts.
Regarding claim 18, claim 6 of the ‘007 recites the polymeric structures can comprise polysaccharides such as chitosan.
Regarding claims 24, claims of the ‘007 do not disclose that the hydrogel comprises TEMED. As discussed above, Ochi discloses a method of preparing hydrogel capsules (page 605, column 1, ¶ 5). Ochi discloses that the hydrogel capsule can comprise TEMED as a polymerization accelerator (page 605, column 1, ¶ 5). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use TEMED for preparing polymerized hydrogels of the ‘007 more efficiently. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ochi teaches that TEMED can be used as a polymerization accelerator when preparing hydrogel capsules. Further, a person of ordinary skill in the art would have been motivated to utilize TEMED to drive the free-radical crosslinking of monomers such as acrylamide into a solid hydrogel shell, allowing rapid, controlled polymerization at room temperature for encapsulating drugs or cells without heat damage.
Regarding claim 31, claim 1 of the ‘007 recites that the permeability of layer limits entry of immune cells, antibodies and cytokines. Claims of the ‘007 do not disclose that the outer shell is semi-permeable. As discussed above, Ma discloses hydrogel capsules encapsulating cells for therapeutical applications (abstract). Ma discloses the fabrication of core-shell capsules with the shell fluid consists of a cell-free alginate solution, while the core fluid contains therapeutic cells (¶ 99). Ma discloses that the surface of the microcapsules can be crosslinked with polyamino acids to form a semi-permeable membrane (¶ 102). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the capsules of the ‘007 by making the outer shell semi-permeable. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ma teaches that the outer shell can be semi-permeable. Further, a person of ordinary skill in the art would have been motivated to utilize semi-permeable outer shell in order to allow selective permeability for nutrient and target analytes.
Regarding claims 55, claims of the ‘007 do not disclose a specific engineered bacterial biosensor such as E. coli. As discussed above, Sayler discloses that the genetically modified bacterium can be E. coli (claim 23). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use E. coli as engineered bacterial biosensor encapsulated in the hydrogel capsules of the ‘007 for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches that E. coli can be used as engineered bacterial biosensor. Further, a person of ordinary skill in the art would have been motivated to utilize E. coli as a well-studied, heavily characterized bacterium for efficient genetic modifications.
Regarding claim 64, claims of the ‘007 do not disclose that the engineered bacterial biosensor expresses a specific molecule such as DNA. As discussed above, Sayler discloses that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte (FIG. 1). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to encapsulate engineered bacterial biosensor expressing a reporter DNA in the hydrogel capsules of the ‘007 for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte.
Claims 1, 3-8, 11-15, 18, 24, 27, 30, 31, 55, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. US 10,172,791 (cited on PTO-892) in view of Sayler et al. (US 2003 0108980; cited on IDS filed September 04, 2024), Degen et al. (Journal of Physics: Condensed Matter, 2015; cited on PTO-892), Chawarai et al. (US 2016 0128944; cited on PTO-892), Wang et al. (RSC advances, 2013; cited on PTO-892), Guo et al. (BioResources, 2020; cited on PTO-892), Ochi et al. (Advanced Powder Technology, 2014; cited on PTO-892), and Ma et al. (US 2014 0271843; cited on PTO-892).
Regarding claims 1, 27, and 30, claim 10 of the ‘791 recites hydrogel capsules encapsulating cells. Claim 16 of the ‘791 recites the hydrogel capsules can have core-shell structures and the core can comprise cells. Claims of the ‘791 do not recite engineered bacterial biosensor. As discussed above, Sayler discloses a device comprising a genetically modified (engineered) bacterium producing a bioluminescent protein in the presence of divalent mercury (biosensor) (claim 14). Sayler discloses that the bacterium can be encapsulated in a matrix such as alginate (hydrogel) (claim 15). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogen capsules of the ‘791 by replacing the cells with engineered bacterial biosensor for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches engineered bacterial biosensor can be encapsulated in a hydrogel matrix. Further, a person of ordinary skill in the art would have been motivated to utilize the engineered bacterial biosensor in order to expand the applications of the capsules of the ’486.
Regarding claims 3, claim 6 of the ‘791 recites the polymer can comprise polysaccharides such as alginate.
Regarding claim 4, claims of the ‘791 do not recite that the alginate is present at a concentration of 0.1- 10 weight percent. As discussed above, Degen discloses magneto-responsive alginate capsules (title). Degen discloses that 2% wt concentration of alginate can be used for preparing the alginate capsules (page 4, column 1, ¶ 4). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘791 by using a 2 wt% concentration of alginate. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Degen teaches that a 2 wt% concentration of alginate can be used for preparing capsules. Further, a person of ordinary skill in the art would have been motivated to optimize the amount of alginate according to the specific requirements of the application. The concentration of alginate is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of the alginate for achieving the desired characteristics of the capsules as the concentration of alginate critically determines the characteristics such as size, shape, stability, permeability, and encapsulation efficiency.
Regarding claims 5-8, claims of the ‘791 do not recite that the hydrogel matrix is paramagnetic and that the hydrogel matrix further comprises a magnetic small material or nanoscale material such as iron oxide. As discussed above, Degen discloses that the hydrogel matrix is paramagnetic and that the hydrogel matrix further comprises a magnetic small material or nanoscale material such as iron oxide (instant claims 5-8). As discussed above, Degen discloses that different kinds of magnetic nanoparticles (mNPs) such as superparamagnetic iron oxide can be incorporated in different locations of the capsule such as in the matrix of the beads, in the core, or inside the shell of the capsules (page 2, column 1, ¶ 4; page 9, column 2, ¶ 2). Degen discloses that these magneto-responsive systems have a wide range of potential applications such as drug delivery systems, especially the capsules with mNPs solely inside the shell can be interesting for pharmaceutical application because no magnetic material will be released by a capsule break (abstract; page 10, column 1, ¶ 1). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘791 by incorporating paramagnetic iron oxide nanoparticles into the hydrogel matrix to expand the applications of the device. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Degen teaches that paramagnetic nanoparticles such as iron oxide can be incorporated into the alginate matrix for pharmaceutical applications. Further, a person of ordinary skill in the art would have been motivated to combine iron oxide nanoparticles with alginate matrix in order to create a multifunctional composite for biomedical applications such magnetic resonance imaging (MRI) and magnetic targeting and delivery.
Regarding claims 11-15, claims of the ‘791 do not recite that the hydrogel matrix further comprises an ultraviolet (UV) absorbent small molecule such as photoabsorber or tartrazine; or nanoscale material such as natural polymer or titanium oxide. As discussed above, Chawarai discloses a particle comprising an active agent, a core and a coating layer (claim 94). Chawarai discloses that the active agent can be present in the core or the coating layer and that the active agent can be UV light absorbing agents such as benzophenone (photoabsorber) (claim 96; claim 100; ¶ 182; ¶ 233). Chawarai discloses that the active agent can be tartrazine or titanium oxide (¶ 21; ¶ 71). As discussed above, Wang discloses polypropylene (PP)/Mg3Al–tartrazine layered double hydroxide (LDH) nanocomposites for enhanced UV absorption (abstract). Wang discloses that tartrazine can be an excellent UV absorber (page 26017, column 2, ¶ 3). As discussed above, Guo discloses that lignin-TiO2 (titanium dioxide)@NFC (nanofibrillated cellulose) composites (nanoparticles) shows a good UV light absorption (abstract). Guo discloses that TiO2 have an ability to absorb a wide range of UV radiation, and that lignin (natural polymer) can have a property of UV-absorption (Page 7374, ¶ 2; page 7375, ¶ 5). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘791 by incorporating a UV absorbent small molecule or nanoscale material such as benzophenone, tartrazine, titanium oxide, or lignin nanoparticles into the hydrogel matrix to improve the capsules by preventing UV damage. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Chawarai teaches that the capsules can comprise UV light absorbing agents like benzophenone; Wang teaches tartrazine can be used as a UV absorber; and Guo teaches that TiO2 and lignin can be used as UV absorbers. Further, a person of ordinary skill in the art would have been motivated to utilize such a UV absorber for the capsules in order to protect the living bacterial biosensors from UV damage, prevent the hydrogel matrix from degrading, and reduce optical noise and signal interference for accurate sensor readouts.
Regarding claim 18, claim 6 of the ‘791 recites the polymeric structures can comprise polysaccharides such as chitosan.
Regarding claims 24, claims of the ‘791 do not disclose that the hydrogel comprises TEMED. As discussed above, Ochi discloses a method of preparing hydrogel capsules (page 605, column 1, ¶ 5). Ochi discloses that the hydrogel capsule can comprise TEMED as a polymerization accelerator (page 605, column 1, ¶ 5). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use TEMED to prepare polymerized hydrogels of the ‘791 more efficiently. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ochi teaches that TEMED can be used as a polymerization accelerator when preparing hydrogel capsules. Further, a person of ordinary skill in the art would have been motivated to utilize TEMED to drive the free-radical crosslinking of monomers such as acrylamide into a solid hydrogel shell, allowing rapid, controlled polymerization at room temperature for encapsulating drugs or cells without heat damage.
Regarding claim 31, claim 16 of the ‘791 recites that the permeability of the outer acellular barrier layer limits entry of immune cells, antibodies and cytokines. Claims of the ‘791 do not disclose that the outer shell is semi-permeable. As discussed above, Ma discloses hydrogel capsules encapsulating cells for therapeutical applications (abstract). Ma discloses the fabrication of core-shell capsules with the shell fluid consists of a cell-free alginate solution, while the core fluid contains therapeutic cells (¶ 99). Ma discloses that the surface of the microcapsules can be crosslinked with polyamino acids to form a semi-permeable membrane (¶ 102). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the capsules of the ‘791 by making the outer shell semi-permeable. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ma teaches that the outer shell can be semi-permeable. Further, a person of ordinary skill in the art would have been motivated to utilize semi-permeable outer shell in order to allow selective permeability for nutrient and target analytes.
Regarding claims 55, claims of the ‘791 do not disclose a specific engineered bacterial biosensor such as E. coli. As discussed above, Sayler discloses that the genetically modified bacterium can be E. coli (claim 23). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use E. coli as engineered bacterial biosensor encapsulated in the hydrogel capsules of the ‘791 for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches that E. coli can be used as engineered bacterial biosensor. Further, a person of ordinary skill in the art would have been motivated to utilize E. coli as a well-studied, heavily characterized bacterium for efficient genetic modifications.
Regarding claim 64, claims of the ‘791 do not disclose that the engineered bacterial biosensor expresses a specific molecule such as DNA. engineered bacterial biosensor such as E. coli. As discussed above, Sayler discloses that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte (FIG. 1). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to encapsulate engineered bacterial biosensor expressing a reporter DNA in the hydrogel capsules of the ‘791 for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte.
Claims 1, 3-8, 11-15, 18, 24, 27, 30, 31, 55, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. US 10,786,446 (cited on IDS filed September 4, 2024) in view of Sayler et al. (US 2003 0108980; cited on IDS filed September 04, 2024), Degen et al. (Journal of Physics: Condensed Matter, 2015; cited on PTO-892), Chawarai et al. (US 2016 0128944; cited on PTO-892), Wang et al. (RSC advances, 2013; cited on PTO-892), Guo et al. (BioResources, 2020; cited on PTO-892), Ochi et al. (Advanced Powder Technology, 2014; cited on PTO-892), and Ma et al. (US 2014 0271843; cited on PTO-892).
Regarding claims 1, 27, and 30, claim 1 of the ‘446 recites hydrogel capsules encapsulating mammalian cells. Claim 1 of the ‘446 recites the hydrogel capsules can have core-shell structures and the core can comprise cells. Claims of the ‘446 do not recite engineered bacterial biosensor. As discussed above, Sayler discloses a device comprising a genetically modified (engineered) bacterium producing a bioluminescent protein in the presence of divalent mercury (biosensor) (claim 14). Sayler discloses that the bacterium can be encapsulated in a matrix such as alginate (hydrogel) (claim 15). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogen capsules of the ‘446 by replacing the cells with engineered bacterial biosensor for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches engineered bacterial biosensor can be encapsulated in a hydrogel matrix. Further, a person of ordinary skill in the art would have been motivated to utilize the engineered bacterial biosensor in order to expand the applications of the capsules of the ’486.
Regarding claims 3, claim 7 of the ‘446 recites the polymer can comprise polysaccharides such as alginate.
Regarding claim 4, claims of the ‘446 do not recite that the alginate is present at a concentration of 0.1- 10 weight percent. As discussed above, Degen discloses magneto-responsive alginate capsules (title). Degen discloses that 2% wt concentration of alginate can be used for preparing the alginate capsules (page 4, column 1, ¶ 4). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘446 by using a 2 wt% concentration of alginate. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Degen teaches that a 2 wt% concentration of alginate can be used for preparing capsules. Further, a person of ordinary skill in the art would have been motivated to optimize the amount of alginate according to the specific requirements of the application. The concentration of alginate is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of the alginate for achieving the desired characteristics of the capsules as the concentration of alginate critically determines the characteristics such as size, shape, stability, permeability, and encapsulation efficiency.
Regarding claims 5-8, claims of the ‘446 do not recite that the hydrogel matrix is paramagnetic and that the hydrogel matrix further comprises a magnetic small material or nanoscale material such as iron oxide. As discussed above, Degen discloses that the hydrogel matrix is paramagnetic and that the hydrogel matrix further comprises a magnetic small material or nanoscale material such as iron oxide (instant claims 5-8). As discussed above, Degen discloses that different kinds of magnetic nanoparticles (mNPs) such as superparamagnetic iron oxide can be incorporated in different locations of the capsule such as in the matrix of the beads, in the core, or inside the shell of the capsules (page 2, column 1, ¶ 4; page 9, column 2, ¶ 2). Degen discloses that these magneto-responsive systems have a wide range of potential applications such as drug delivery systems, especially the capsules with mNPs solely inside the shell can be interesting for pharmaceutical application because no magnetic material will be released by a capsule break (abstract; page 10, column 1, ¶ 1). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘446 by incorporating paramagnetic iron oxide nanoparticles into the hydrogel matrix to expand the applications of the device. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Degen teaches that paramagnetic nanoparticles such as iron oxide can be incorporated into the alginate matrix for pharmaceutical applications. Further, a person of ordinary skill in the art would have been motivated to combine iron oxide nanoparticles with alginate matrix in order to create a multifunctional composite for biomedical applications such magnetic resonance imaging (MRI) and magnetic targeting and delivery.
Regarding claims 11-15, claims of the ‘446 do not recite that the hydrogel matrix further comprises an ultraviolet (UV) absorbent small molecule such as photoabsorber or tartrazine; or nanoscale material such as natural polymer or titanium oxide. As discussed above, Chawarai discloses a particle comprising an active agent, a core and a coating layer (claim 94). Chawarai discloses that the active agent can be present in the core or the coating layer and that the active agent can be UV light absorbing agents such as benzophenone (photoabsorber) (claim 96; claim 100; ¶ 182; ¶ 233). Chawarai discloses that the active agent can be tartrazine or titanium oxide (¶ 21; ¶ 71). As discussed above, Wang discloses polypropylene (PP)/Mg3Al–tartrazine layered double hydroxide (LDH) nanocomposites for enhanced UV absorption (abstract). Wang discloses that tartrazine can be an excellent UV absorber (page 26017, column 2, ¶ 3). As discussed above, Guo discloses that lignin-TiO2 (titanium dioxide)@NFC (nanofibrillated cellulose) composites (nanoparticles) shows a good UV light absorption (abstract). Guo discloses that TiO2 have an ability to absorb a wide range of UV radiation, and that lignin (natural polymer) can have a property of UV-absorption (Page 7374, ¶ 2; page 7375, ¶ 5). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘446 by incorporating a UV absorbent small molecule or nanoscale material such as benzophenone, tartrazine, titanium oxide, or lignin nanoparticles into the hydrogel matrix to improve the capsules by preventing UV damage. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Chawarai teaches that the capsules can comprise UV light absorbing agents like benzophenone; Wang teaches tartrazine can be used as a UV absorber; and Guo teaches that TiO2 and lignin can be used as UV absorbers. Further, a person of ordinary skill in the art would have been motivated to utilize such a UV absorber for the capsules in order to protect the living bacterial biosensors from UV damage, prevent the hydrogel matrix from degrading, and reduce optical noise and signal interference for accurate sensor readouts.
Regarding claim 18, claim 7 of the ‘446 recites the polymeric structures can comprise polysaccharides such as chitosan.
Regarding claims 24, claims of the ‘446 do not disclose that the hydrogel comprises TEMED. As discussed above, Ochi discloses a method of preparing hydrogel capsules (page 605, column 1, ¶ 5). Ochi discloses that the hydrogel capsule can comprise TEMED as a polymerization accelerator (page 605, column 1, ¶ 5). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use TEMED to prepare polymerized hydrogels of the ‘446 more efficiently. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ochi teaches that TEMED can be used as a polymerization accelerator when preparing hydrogel capsules. Further, a person of ordinary skill in the art would have been motivated to utilize TEMED to drive the free-radical crosslinking of monomers such as acrylamide into a solid hydrogel shell, allowing rapid, controlled polymerization at room temperature for encapsulating drugs or cells without heat damage.
Regarding claim 31, claims of the ‘446 do not disclose that the outer shell is semi-permeable. As discussed above, Ma discloses hydrogel capsules encapsulating cells for therapeutical applications (abstract). Ma discloses the fabrication of core-shell capsules with the shell fluid consists of a cell-free alginate solution, while the core fluid contains therapeutic cells (¶ 99). Ma discloses that the surface of the microcapsules can be crosslinked with polyamino acids to form a semi-permeable membrane (¶ 102). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the capsules of the ‘446 by making the outer shell semi-permeable. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ma teaches that the outer shell can be semi-permeable. Further, a person of ordinary skill in the art would have been motivated to utilize semi-permeable outer shell in order to allow selective permeability for nutrient and target analytes.
Regarding claims 55, claims of the ‘446 do not disclose a specific engineered bacterial biosensor such as E. coli. As discussed above, Sayler discloses that the genetically modified bacterium can be E. coli (claim 23). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use E. coli as engineered bacterial biosensor encapsulated in the hydrogel capsules of the ‘446 for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches that E. coli can be used as engineered bacterial biosensor. Further, a person of ordinary skill in the art would have been motivated to utilize E. coli as a well-studied, heavily characterized bacterium for efficient genetic modifications.
Regarding claim 64, claims of the ‘446 do not disclose that the engineered bacterial biosensor expresses a specific molecule such as DNA. engineered bacterial biosensor such as E. coli. As discussed above, Sayler discloses that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte (FIG. 1). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to encapsulate engineered bacterial biosensor expressing a reporter DNA in the hydrogel capsules of the ‘446 for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte.
Claims 1, 3-8, 11-15, 18, 24, 27, 30, 31, 55, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. US 10,835,486 (cited on PTO-892) in view of Sayler et al. (US 2003 0108980; cited on IDS filed September 04, 2024), Degen et al. (Journal of Physics: Condensed Matter, 2015; cited on PTO-892), Chawarai et al. (US 2016 0128944; cited on PTO-892), Wang et al. (RSC advances, 2013; cited on PTO-892), Guo et al. (BioResources, 2020; cited on PTO-892), Ochi et al. (Advanced Powder Technology, 2014; cited on PTO-892), and Ma et al. (US 2014 0271843; cited on PTO-892).
Regarding claims 1, 27, and 30, claim 1 of the ‘486 recites hydrogel capsules encapsulating cells. Claim 6 of the ‘486 recites the hydrogel capsules can have core-shell structures and the core can comprise cells. Claims of the ‘486 do not recite engineered bacterial biosensor. As discussed above, Sayler discloses a device comprising a genetically modified (engineered) bacterium producing a bioluminescent protein in the presence of divalent mercury (biosensor) (claim 14). Sayler discloses that the bacterium can be encapsulated in a matrix such as alginate (hydrogel) (claim 15). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogen capsules of the ‘486 by replacing the cells with engineered bacterial biosensor for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches engineered bacterial biosensor can be encapsulated in a hydrogel matrix. Further, a person of ordinary skill in the art would have been motivated to utilize the engineered bacterial biosensor in order to expand the applications of the capsules of the ’486.
Regarding claims 3, claim 3 of the ‘486 recites the polymeric structures can comprise polysaccharides such as alginates.
Regarding claim 4, claims of the ‘486 do not recite that the alginate is present at a concentration of 0.1- 10 weight percent. As discussed above, Degen discloses magneto-responsive alginate capsules (title). Degen discloses that 2% wt concentration of alginate can be used for preparing the alginate capsules (page 4, column 1, ¶ 4). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘486 by using a 2 wt% concentration of alginate. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Degen teaches that a 2 wt% concentration of alginate can be used for preparing capsules. Further, a person of ordinary skill in the art would have been motivated to optimize the amount of alginate according to the specific requirements of the application. The concentration of alginate is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of the alginate for achieving the desired characteristics of the capsules as the concentration of alginate critically determines the characteristics such as size, shape, stability, permeability, and encapsulation efficiency.
Regarding claims 5-8, claims of the ‘486 do not recite that the hydrogel matrix is paramagnetic and that the hydrogel matrix further comprises a magnetic small material or nanoscale material such as iron oxide. As discussed above, Degen discloses that the hydrogel matrix is paramagnetic and that the hydrogel matrix further comprises a magnetic small material or nanoscale material such as iron oxide (instant claims 5-8). As discussed above, Degen discloses that different kinds of magnetic nanoparticles (mNPs) such as superparamagnetic iron oxide can be incorporated in different locations of the capsule such as in the matrix of the beads, in the core, or inside the shell of the capsules (page 2, column 1, ¶ 4; page 9, column 2, ¶ 2). Degen discloses that these magneto-responsive systems have a wide range of potential applications such as drug delivery systems, especially the capsules with mNPs solely inside the shell can be interesting for pharmaceutical application because no magnetic material will be released by a capsule break (abstract; page 10, column 1, ¶ 1). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘486 by incorporating paramagnetic iron oxide nanoparticles into the hydrogel matrix to expand the applications of the device. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Degen teaches that paramagnetic nanoparticles such as iron oxide can be incorporated into the alginate matrix for pharmaceutical applications. Further, a person of ordinary skill in the art would have been motivated to combine iron oxide nanoparticles with alginate matrix in order to create a multifunctional composite for biomedical applications such magnetic resonance imaging (MRI) and magnetic targeting and delivery.
Regarding claims 11-15, claims of the ‘486 do not recite that the hydrogel matrix further comprises an ultraviolet (UV) absorbent small molecule such as photoabsorber or tartrazine; or nanoscale material such as natural polymer or titanium oxide. As discussed above, Chawarai discloses a particle comprising an active agent, a core and a coating layer (claim 94). Chawarai discloses that the active agent can be present in the core or the coating layer and that the active agent can be UV light absorbing agents such as benzophenone (photoabsorber) (claim 96; claim 100; ¶ 182; ¶ 233). Chawarai discloses that the active agent can be tartrazine or titanium oxide (¶ 21; ¶ 71). As discussed above, Wang discloses polypropylene (PP)/Mg3Al–tartrazine layered double hydroxide (LDH) nanocomposites for enhanced UV absorption (abstract). Wang discloses that tartrazine can be an excellent UV absorber (page 26017, column 2, ¶ 3). As discussed above, Guo discloses that lignin-TiO2 (titanium dioxide)@NFC (nanofibrillated cellulose) composites (nanoparticles) shows a good UV light absorption (abstract). Guo discloses that TiO2 have an ability to absorb a wide range of UV radiation, and that lignin (natural polymer) can have a property of UV-absorption (Page 7374, ¶ 2; page 7375, ¶ 5). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘486 by incorporating a UV absorbent small molecule or nanoscale material such as benzophenone, tartrazine, titanium oxide, or lignin nanoparticles into the hydrogel matrix to improve the capsules by preventing UV damage. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Chawarai teaches that the capsules can comprise UV light absorbing agents like benzophenone; Wang teaches tartrazine can be used as a UV absorber; and Guo teaches that TiO2 and lignin can be used as UV absorbers. Further, a person of ordinary skill in the art would have been motivated to utilize such a UV absorber for the capsules in order to protect the living bacterial biosensors from UV damage, prevent the hydrogel matrix from degrading, and reduce optical noise and signal interference for accurate sensor readouts.
Regarding claim 18, claim 3 of the ‘486 recites the polymeric structures can comprise polysaccharides such as chitosan.
Regarding claims 24, claims of the ‘486 do not disclose that the hydrogel comprises TEMED. As discussed above, Ochi discloses a method of preparing hydrogel capsules (page 605, column 1, ¶ 5). Ochi discloses that the hydrogel capsule can comprise TEMED as a polymerization accelerator (page 605, column 1, ¶ 5). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use TEMED to prepare polymerized hydrogels of the ‘486 more efficiently. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ochi teaches that TEMED can be used as a polymerization accelerator when preparing hydrogel capsules. Further, a person of ordinary skill in the art would have been motivated to utilize TEMED to drive the free-radical crosslinking of monomers such as acrylamide into a solid hydrogel shell, allowing rapid, controlled polymerization at room temperature for encapsulating drugs or cells without heat damage.
Regarding claim 31, claims of the ‘486 do not disclose that the outer shell is semi-permeable. As discussed above, Ma discloses hydrogel capsules encapsulating cells for therapeutical applications (abstract). Ma discloses the fabrication of core-shell capsules with the shell fluid consists of a cell-free alginate solution, while the core fluid contains therapeutic cells (¶ 99). Ma discloses that the surface of the microcapsules can be crosslinked with polyamino acids to form a semi-permeable membrane (¶ 102). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘486 by making the outer shell semi-permeable. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ma teaches that the outer shell can be semi-permeable. Further, a person of ordinary skill in the art would have been motivated to utilize semi-permeable outer shell in order to allow selective permeability for nutrient and target analytes.
Regarding claims 55, claims of the ‘486 do not disclose a specific engineered bacterial biosensor such as E. coli. As discussed above, Sayler discloses that the genetically modified bacterium can be E. coli (claim 23). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use E. coli as engineered bacterial biosensor encapsulated in the hydrogel capsules of the ‘486 for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches that E. coli can be used as engineered bacterial biosensor. Further, a person of ordinary skill in the art would have been motivated to utilize E. coli as a well-studied, heavily characterized bacterium for efficient genetic modifications.
Regarding claim 64, claims of the ‘486 do not disclose that the engineered bacterial biosensor expresses a specific molecule such as DNA. engineered bacterial biosensor such as E. coli. As discussed above, Sayler discloses that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte (FIG. 1). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to encapsulate engineered bacterial biosensor expressing a reporter DNA in the hydrogel capsules of the ‘486 for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte.
Claims 1, 3-8, 11-15, 18, 24, 27, 30, 31, 55, and 64 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/703,201 (US 2024 0415931; cited on PTO-892) in view of Sayler et al. (US 2003 0108980; cited on IDS filed September 04, 2024), Degen et al. (Journal of Physics: Condensed Matter, 2015; cited on PTO-892), Chawarai et al. (US 2016 0128944; cited on PTO-892), Wang et al. (RSC advances, 2013; cited on PTO-892), Guo et al. (BioResources, 2020; cited on PTO-892), Ochi et al. (Advanced Powder Technology, 2014; cited on PTO-892), and Ma et al. (US 2014 0271843; cited on PTO-892).
Regarding claims 1, 27, and 30, claim 22 of the ‘201 recites hydrogel capsules encapsulating cells. Claims of the ‘201 do not recite engineered bacterial biosensor. As discussed above, Sayler discloses a device comprising a genetically modified (engineered) bacterium producing a bioluminescent protein in the presence of divalent mercury (biosensor) (claim 14). Sayler discloses that the bacterium can be encapsulated in a matrix such as alginate (hydrogel) (claim 15). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogen capsules of the ‘201 by replacing the cells with engineered bacterial biosensor for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches engineered bacterial biosensor can be encapsulated in a hydrogel matrix. Further, a person of ordinary skill in the art would have been motivated to utilize the engineered bacterial biosensor in order to expand the applications of the capsules of the ’486.
Regarding claims 3, claim 22 of the ‘201 recites the hydrogel can be alginate.
Regarding claim 4, claims of the ‘201 do not recite that the alginate is present at a concentration of 0.1- 10 weight percent. As discussed above, Degen discloses magneto-responsive alginate capsules (title). Degen discloses that 2% wt concentration of alginate can be used for preparing the alginate capsules (page 4, column 1, ¶ 4). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘201 by using a 2 wt% concentration of alginate. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Degen teaches that a 2 wt% concentration of alginate can be used for preparing capsules. Further, a person of ordinary skill in the art would have been motivated to optimize the amount of alginate according to the specific requirements of the application. The concentration of alginate is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of the alginate for achieving the desired characteristics of the capsules as the concentration of alginate critically determines the characteristics such as size, shape, stability, permeability, and encapsulation efficiency.
Regarding claims 5-8, claims of the ‘201 do not recite that the hydrogel matrix is paramagnetic and that the hydrogel matrix further comprises a magnetic small material or nanoscale material such as iron oxide. As discussed above, Degen discloses that the hydrogel matrix is paramagnetic and that the hydrogel matrix further comprises a magnetic small material or nanoscale material such as iron oxide (instant claims 5-8). As discussed above, Degen discloses that different kinds of magnetic nanoparticles (mNPs) such as superparamagnetic iron oxide can be incorporated in different locations of the capsule such as in the matrix of the beads, in the core, or inside the shell of the capsules (page 2, column 1, ¶ 4; page 9, column 2, ¶ 2). Degen discloses that these magneto-responsive systems have a wide range of potential applications such as drug delivery systems, especially the capsules with mNPs solely inside the shell can be interesting for pharmaceutical application because no magnetic material will be released by a capsule break (abstract; page 10, column 1, ¶ 1). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘201 by incorporating paramagnetic iron oxide nanoparticles into the hydrogel matrix to expand the applications of the device. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Degen teaches that paramagnetic nanoparticles such as iron oxide can be incorporated into the alginate matrix for pharmaceutical applications. Further, a person of ordinary skill in the art would have been motivated to combine iron oxide nanoparticles with alginate matrix in order to create a multifunctional composite for biomedical applications such magnetic resonance imaging (MRI) and magnetic targeting and delivery.
Regarding claims 11-15, claims of the ‘201 do not recite that the hydrogel matrix further comprises an ultraviolet (UV) absorbent small molecule such as photoabsorber or tartrazine; or nanoscale material such as natural polymer or titanium oxide. As discussed above, Chawarai discloses a particle comprising an active agent, a core and a coating layer (claim 94). Chawarai discloses that the active agent can be present in the core or the coating layer and that the active agent can be UV light absorbing agents such as benzophenone (photoabsorber) (claim 96; claim 100; ¶ 182; ¶ 233). Chawarai discloses that the active agent can be tartrazine or titanium oxide (¶ 21; ¶ 71). As discussed above, Wang discloses polypropylene (PP)/Mg3Al–tartrazine layered double hydroxide (LDH) nanocomposites for enhanced UV absorption (abstract). Wang discloses that tartrazine can be an excellent UV absorber (page 26017, column 2, ¶ 3). As discussed above, Guo discloses that lignin-TiO2 (titanium dioxide)@NFC (nanofibrillated cellulose) composites (nanoparticles) shows a good UV light absorption (abstract). Guo discloses that TiO2 have an ability to absorb a wide range of UV radiation, and that lignin (natural polymer) can have a property of UV-absorption (Page 7374, ¶ 2; page 7375, ¶ 5). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the hydrogel capsules of the ‘201 by incorporating a UV absorbent small molecule or nanoscale material such as benzophenone, tartrazine, titanium oxide, or lignin nanoparticles into the hydrogel matrix to improve the capsules by preventing UV damage. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Chawarai teaches that the capsules can comprise UV light absorbing agents like benzophenone; Wang teaches tartrazine can be used as a UV absorber; and Guo teaches that TiO2 and lignin can be used as UV absorbers. Further, a person of ordinary skill in the art would have been motivated to utilize such a UV absorber for the capsules in order to protect the living bacterial biosensors from UV damage, prevent the hydrogel matrix from degrading, and reduce optical noise and signal interference for accurate sensor readouts.
Regarding claim 18, claim 22 of the ‘201 recites the hydrogel can be chitosan.
Regarding claims 24, claims of the ‘201 do not disclose that the hydrogel comprises TEMED. As discussed above, Ochi discloses a method of preparing hydrogel capsules (page 605, column 1, ¶ 5). Ochi discloses that the hydrogel capsule can comprise TEMED as a polymerization accelerator (page 605, column 1, ¶ 5). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use TEMED to prepare polymerized hydrogels of the ‘201 more efficiently. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ochi teaches that TEMED can be used as a polymerization accelerator when preparing hydrogel capsules. Further, a person of ordinary skill in the art would have been motivated to utilize TEMED to drive the free-radical crosslinking of monomers such as acrylamide into a solid hydrogel shell, allowing rapid, controlled polymerization at room temperature for encapsulating drugs or cells without heat damage.
Regarding claim 31, claims of the ‘201 do not disclose that the outer shell is semi-permeable. As discussed above, Ma discloses hydrogel capsules encapsulating cells for therapeutical applications (abstract). Ma discloses the fabrication of core-shell capsules with the shell fluid consists of a cell-free alginate solution, while the core fluid contains therapeutic cells (¶ 99). Ma discloses that the surface of the microcapsules can be crosslinked with polyamino acids to form a semi-permeable membrane (¶ 102). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the capsules of the ‘201 by making the outer shell semi-permeable. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Ma teaches that the outer shell can be semi-permeable. Further, a person of ordinary skill in the art would have been motivated to utilize semi-permeable outer shell in order to allow selective permeability for nutrient and target analytes.
Regarding claims 55, claims of the ‘201 do not disclose a specific engineered bacterial biosensor such as E. coli. As discussed above, Sayler discloses that the genetically modified bacterium can be E. coli (claim 23). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use E. coli as engineered bacterial biosensor encapsulated in the hydrogel capsules of the ‘201 for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches that E. coli can be used as engineered bacterial biosensor. Further, a person of ordinary skill in the art would have been motivated to utilize E. coli as a well-studied, heavily characterized bacterium for efficient genetic modifications.
Regarding claim 64, claims of the ‘201 do not disclose that the engineered bacterial biosensor expresses a specific molecule such as DNA. engineered bacterial biosensor such as E. coli. As discussed above, Sayler discloses that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte (FIG. 1). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to encapsulate engineered bacterial biosensor expressing a reporter DNA in the hydrogel capsules of the ‘201 for applications in diagnostics. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Sayler teaches that the genetically modified bacterium can express a reporter gene (DNA) upon exposure to a specific analyte.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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