DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 5, 12, 14-40, 45-51, and 55-58 are canceled.
Claims 1-4, 6-11, 13, 41-44, 52-54, and 59-60 are pending.
Claims 1-4, 6-11, 13, 41-44, 52-54, and 59-60 are examined herein.
Election/Restrictions
Applicant's election with traverse of the election of species requirement in the reply filed on 08/08/2025 is acknowledged. The traversal is on the ground(s) that any prior art searched for the elected Species would be applicable to the non-elected Species. Hence, there would not be a serious search and/or examination burden.
This is not found persuasive because a search for the method in the elected species of plant cells will require a unique search from the non-elected species of animal and microorganism cells. Therefore, a search burden IS present because the species have acquired a separate status in the art in view of their classification, have divergent subject matter, and require a different field of search.
The requirement is still deemed proper and is therefore made FINAL.
Priority
Application No. 17/922,908 filed on 11/02/2022 is a 371 of PCT Application No. PCT/US2021/030614 filed on 05/04/2021 which claims priority to provisional application No. 63/019,766 filed on 05/04/2020.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-4, 6-9, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Barnett (US-20110104052-A1).
Claim 1 is drawn to a method of modifying an environment of a cell in a droplet (104), the method comprising: a. encapsulating the cell (102) and a controlled release particle (103) in the droplet (104), wherein the controlled release particle (103) comprises a cargo; and b. activating release of the cargo from the controlled release particle (103), wherein the droplet (104) remains intact during activation, wherein release of the cargo changes the environment in the droplet.
Claim 2 is drawn to the method of claim 1, wherein the cell (102) is an animal cell, plant cell, algae cell, bacterial cell, fungal cell, protoplast, pollen grain, microspore, or tetrad.
Claim 3 is drawn to the method of claim 1, wherein the cargo comprises one or more chemicals or biomolecules.
Claim 4 is drawn to the method of claim 3, wherein the one or more chemicals or biomolecules have pharmacological activity, signaling activity, biological activity, pH activity, or biochemical activity.
Claim 6 is drawn to the method of claim 1, wherein the cargo is released by a mechanism selected from ultrasound, magnetism, physical contact of the particle with the cell, light, pH, or temperature changes.
Claim 7 is drawn to the method of claim 1, wherein the controlled release particle (103) has a solid core, a semi-solid core, a liquid core, or a gas core.
Claim 8 is drawn to the method of claim 1, wherein the controlled release particle (103) comprises multiple layers, each layer having a same or different chemical from that of the other layers.
Claim 9 is drawn to the method of claim 1, wherein release of the cargo affects the cell.
Claim 11 is drawn to the method of claim 9, wherein release of the cargo modulates cell development.
Regarding claim 1, Barnett teaches a method forming a droplet comprising: a) a cell and/or biological agent, a PEGDA polymer that is not crosslinked with a paramagnetic or superparamagnetic metal, and at least one of a paramagnetic or a superparamagnetic metal (¶0397) (i.e. encapsulating a cell and a particle in a droplet).
However, Barnett does not explicitly teach in a single embodiment:
the particle is a controlled release particle
activating release of the cargo from the controlled release particle (103), wherein the droplet (104) remains intact during activation, wherein release of the cargo changes the environment in the droplet
In an alternative embodiment, Barnett teaches the invention provides a method for the controlled release of an agent in a subject, the method comprising the steps of first administering to the subject iron oxide containing PEGDA chemospheres and then applying an alternating magnetic field that causes a heat based release of the agent from chemospheres/chemogel (i.e. the particle is a controlled release particle, and activating release of the cargo from the controlled release particle) (¶0405). Barnett also teaches that an alternate strategy for enabling slow release of agent from a polymer is through incorporation of nanoparticles in the polymer that interact with the therapeutic agent, and in such a system a synergistic effect is achieved between the polymer and nanoparticle components thereby enabling a slower release profile of therapeutic agents than either polymer or nanoparticle alone (¶0008). Furthermore, Barnett teaches the release of drugs from liposomes, wherein the liposomes remained intact after drug release (¶0214, Fig. 30, example 2). Barnett teaches water-soluble drugs can easily be dissolved in PEGDA and become trapped in the resulting matrix allowing for controlled drug diffusion, and further teaches exemplary agents include, but are not limited to, chemotherapeutic agents (¶0513) (i.e. release of the drug would change the environment to one that would comprise the drug, therefore release of the cargo changes the environment of the droplet).
Regarding claim 2, Barnett teaches in some embodiments of the invention, the cell that may be encapsulated is a mammalian cell (¶0421) (i.e. an animal cell).
Regarding claims 3 and 4, Barnett teaches exemplary agents include, but are not limited to, chemotherapeutic agents (¶0513) (i.e. one chemical or biochemical having pharmacological activity).
Regarding claim 6, Barnett teaches applying an alternating magnetic field that causes a heat based release of the agent from chemospheres/chemogel (¶0405) (i.e. the cargo is released by magnetism and temperature changes).
Regarding claim 7, Barnett teaches the previously referenced nanoparticles used for an alternate strategy for enabling slow release of agent have an aqueous core (¶0050) (i.e. wherein the controlled release particle has a liquid core).
Regarding claim 8, Barnett teaches liposome bilayer membrane particles or vesicles can be prepared with an internal aqueous compartment and a polar surface that takes the shape of unilamellar or multilamellar spherical vesicles (i.e. the controlled release particle comprises multiple layers having different chemical forms).
Regarding claim 9, Barnett teaches iron oxides can be employed for thermal ablation therapy, and when exposed to an alternating magnetic field (AMF), iron oxides in chemospheres heat (¶0356). Barnett teaches drug-loaded chemospheres can be utilized to simultaneously release drug while heating nearby cells (¶0356) (i.e. release of the cargo affects the cell).
Regarding claim 11, Barnett teaches the therapeutic agent may be a growth factor (¶0363) (i.e. the cargo modulates cell development).
Barnett teaches all of the limitations of the rejected claims in alternative embodiments, but does not disclose a single embodiment having all the limitations. As such, the claims are not rejected as anticipated under 35 USC §102 but are instead rejected as obvious under 35 USC §103. One of ordinary skill in the art would have been motivated to combine the limitations as taught by Barnett into a single embodiment to arrive at Applicant’s claimed inventions because each limitation is explicitly taught as an alternative embodiment of the invention. It would therefore be obvious to combine the methods taught by Barnett for the purpose of forming a droplet comprising: a) a cell and/or biological agent, a PEGDA polymer that is not crosslinked with a paramagnetic or superparamagnetic metal, and at least one of a paramagnetic or a superparamagnetic metal (¶0397) wherein an agent is slowly released (¶0008, 0405) as explicitly taught by Barnett. One having ordinary skill in the art would have a reasonable expectation of success because the method Barnett teaches was functional and successful and the application to the alternative embodiments present no special technical obstacles.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Barnett as applied to claims 1 and 9 above, and further in view of Jin (US-20070196281-A1).
Claim 10 is drawn to the method of claim 9, wherein release of the cargo causes lysis of the cell.
Regarding claim 10, Barnett teaches the limitations of claims 1 and 9 as set forth in the previous obviousness rejection. The teachings of Barnett as they are applied to claims 1 and 9 are set forth previously herein and are incorporated by reference.
However, Barnett does not explicitly teach wherein release of the cargo causes lysis of the cell.
In analogous art, Jin teaches a method of oscillating magnetic nanoparticles and applying a remote magnetic field to induce particle movement that causes mechanical disturbance and lysis of cancer cells (¶0021).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention of as taught by Barnett to include the limitations of Jin to arrive at the instantly claimed method with a reasonable expectation of success because Barnett teaches applying an alternating magnetic field that causes a heat based release of the agent from chemospheres/chemogel (¶0405 of Barnett), and incorporation of the method of oscillating magnetic nanoparticles taught by Jin into the method of Barnett for the purpose of cell lysis could be achieved by one of ordinary skill without encountering any special technical difficulties because. One having ordinary skill in the art would have been motivated to do so for the purpose of preferentially damaging cancer cells as taught by Jin (¶0021).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Barnett as applied to claim 1 above, and further in view of Darling (US-20190329210-A1).
Claim 13 is drawn to a drug screening method comprising the method of claim 1, wherein the cargo is a drug compound to be analyzed for its effect on a cell.
Regarding claim 13, Barnett teaches the limitations of claim 1 as set forth in the previous obviousness rejection. The teachings of Barnett as they are applied to claim 1 are set forth previously herein and are incorporated by reference.
However, Barnett does not explicitly teach wherein the cargo is a drug compound to be analyzed for its effect on a cell.
In analogous art, Darling teaches an invention related to Compositions and methods are provided for use of hyper compliant polymer particles in drug delivery (abstract), and teaches CMMPs may be used as a tool for toxicology screening and can be loaded with a drug of interest and delivered into microtissue constructs to test various doses or release profiles (¶0123).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention of as taught by Barnett to include the limitations of Darling to arrive at the instantly claimed method with a reasonable expectation of success because incorporation of the rug screening method taught by Darling into the method of Barnett could be achieved by one of ordinary skill in the art without encountering any special technical obstacles. One having ordinary skill in the art would have been motivated to do so because Darling teaches the method provides a high throughput platform that can deliver more information on the localized effects of the cargo within the more physiologically relevant 3D microtissue constructs (¶0123).
Claims 41-44 and 59-60 are rejected under 35 U.S.C. 103 as being unpatentable over Barnett (US-20110104052-A1) and Lee (WO-2019079787-A1).
Claim 41 is drawn to a method of culturing plant cells, the method comprising: a. encapsulating a plant cell and a controlled release particle (103) in a droplet (104), wherein the controlled release particle (103) comprises a cargo; and b. activating release of the cargo from the controlled release particle (103), wherein the droplet (104) remains intact during activation, and wherein release of the cargo changes a microenvironment of the droplet (104).
Claim 42 is drawn to the method of claim 41, wherein the plant cells are microspores, protoplasts, walled cells, egg cells, or pollen.
Claim 43 is drawn to the method of claim 41, wherein the plant cell has a modified genome.
Claim 44 is drawn to the method of claim 43, wherein the modified genome has been produced by genome editing facilitated by cargo release.
Claim 59 is drawn to the method of claim 44, wherein the genome editing comprises a CRISPR-CAS method.
Claim 60 is drawn to the method of claim 59, wherein the plant cells are pollen.
Regarding claim 41, Barnett teaches a method forming a droplet comprising: a) a cell and/or biological agent, a PEGDA polymer that is not crosslinked with a paramagnetic or superparamagnetic metal, and at least one of a paramagnetic or a superparamagnetic metal (¶0397) (i.e. encapsulating a cell and a particle in a droplet). In an alternative embodiment, Barnet teaches the invention provides a method for the controlled release of an agent in a subject, the method comprising the steps of first administering to the subject iron oxide containing PEGDA chemospheres and then applying an alternating magnetic field that causes a heat based release of the agent from chemospheres/chemogel (i.e. the particle is a controlled release particle, and activating release of the cargo from the controlled release particle) (¶0405). Barnett also teaches that an alternate strategy for enabling slow release of agent from a polymer is through incorporation of nanoparticles in the polymer that interact with the therapeutic agent, and in such a system a synergistic effect is achieved between the polymer and nanoparticle components thereby enabling a slower release profile of therapeutic agents that either polymer or nanoparticle alone (¶0008). Furthermore, Barnett teaches the release of drugs from liposomes, wherein the liposomes remained intact after drug release (¶0214, Fig. 30, example 2). Barnett teaches water-soluble drugs can easily be dissolved in PEGDA and become trapped in the resulting matrix allowing for controlled drug diffusion, and further teaches exemplary agents include, but are not limited to, chemotherapeutic agents (¶0513) (i.e. release of the drug would change the environment to one that would comprise the drug, therefore release of the cargo changes the environment of the droplet).
However, Barnett does not explicitly teach wherein the cell is a plant cell.
Regarding the remaining limitation of claim 41, In analogous art, Lee teaches an invention related to microfluidic systems and methods for transfection using microdroplets encapsulating cells (¶0011). Lee teaches the cells may be plant cells (¶0021).
Regarding claim 42 and 60, Lee teaches the plant cells may be pollen grains (¶0021).
Regarding claims 43, 44, and 59, Lee teaches the invention can be used to perform CRISPR/Cas9 gene editing wherein cells were co-encapsulated with lipoplex comprising plasmid DNA in droplets (00102, 00105, Fig. 1A-B), and specifically teaches knocking out gene expression by delivering CRISPR/Cas9 constructs into cells via droplet lipofection (00103) (i.e. the cell has a modified genome, and the modified genome has been produced by genome editing facilitated by cargo release (the plasmid being the cargo and the release being release of the plasmid DNA from the lipoplex by lipofection).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention of as taught by Barnett to include the limitations of Lee to arrive at the instantly claimed method with a reasonable expectation of success because Lee teaches lipoplexes can harbor plasmid DNA for cell genome modification in a droplet, including plant cells, and incorporation of the plasmid DNA and plant cell into the method taught by Barnett could be achieved without encountering and special technical obstacles. One having ordinary skill in the art would have been motivated to do so for the purpose of improving transfection efficiency and for the purpose of gene editing cells including plant cells, as taught by Lee (¶0012-0013, 0064-0067).
Claims 52-54 are rejected under 35 U.S.C. 103 as being unpatentable over Barnett (US-20110104052-A1), Lee (WO-2019079787-A1), Dirks (US-20080134353-A1), and Brew (Brew-Appiah, R. A., Ankrah, N., Liu, W., Konzak, C. F., von Wettstein, D., & Rustgi, S. (2013). Generation of doubled haploid transgenic wheat lines by microspore transformation. PloS one, 8(11), e80155).
Claim 52 is drawn to a method for creating a microspore derived embryo using encapsulated microspores, the method comprising: a. encapsulating a haploid cell and a controlled release particle (103) in a droplet (104), wherein the controlled release particle (103) comprises a cargo; and b. activating release of the cargo from the controlled release particle (103), wherein the droplet (104) remains intact during activation, and wherein release of the cargo facilitates micropore embryogenesis development.
Claim 53 is drawn to the method of claim 52, wherein the droplet (104) is a hydrogel.
Claim 54 is drawn to the method of claim 52, wherein the cargo is an embryogenesis inducing factor.
Regarding claim 52, Barnett teaches a method forming a droplet comprising: a) a cell and/or biological agent, a PEGDA polymer that is not crosslinked with a paramagnetic or superparamagnetic metal, and at least one of a paramagnetic or a superparamagnetic metal (¶0397) (i.e. encapsulating a cell and a particle in a droplet). In an alternative embodiment, Barnet teaches the invention provides a method for the controlled release of an agent in a subject, the method comprising the steps of first administering to the subject iron oxide containing PEGDA chemospheres and then applying an alternating magnetic field that causes a heat based release of the agent from chemospheres/chemogel (i.e. the particle is a controlled release particle, and activating release of the cargo from the controlled release particle) (¶0405). Barnett also teaches that an alternate strategy for enabling slow release of agent from a polymer is through incorporation of nanoparticles in the polymer that interact with the therapeutic agent, and in such a system a synergistic effect is achieved between the polymer and nanoparticle components thereby enabling a slower release profile of therapeutic agents that either polymer or nanoparticle alone (¶0008). Furthermore, Barnett teaches the release of drugs from liposomes, wherein the liposomes remained intact after drug release (¶0214, Fig. 30, example 2). Barnett teaches water-soluble drugs can easily be dissolved in PEGDA and become trapped in the resulting matrix allowing for controlled drug diffusion, and further teaches exemplary agents include, but are not limited to, chemotherapeutic agents (¶0513) (i.e. release of the drug would change the environment to one that would comprise the drug, therefore release of the cargo changes the environment of the droplet).
Regarding claim 53, Barnett teaches the droplet is a hydrogel sphere (¶0397).
However, Barnett does not explicitly teach:
wherein the cell is a haploid cell, and wherein release of the cargo facilitates microspore embryogenesis development, as required by claim 52.
Wherein the cargo is an embryogenesis inducing factor, as required by claim 54.
Regarding the remaining limitation of claim 52, in analogous art, Lee teaches an invention related to microfluidic systems and methods for transfection of plasmid DNA into cells encapsulated in microdroplets (¶0011), and also teaches the cells may be plant cells including pollen and microspores (¶0021). In other analogous art, Dirks teaches cell division inducing molecules can be expressed in the pollen, for example from a nucleic acid that is present on a plasmid, which may then be used to pollinate egg cells to induce embryogenesis (¶0011, 0020-0023). In other analogous art, Brew teaches plasmid DNA can be transformed into plant cells to induce embryogenesis directly from pollen cells (p. 6, section titled Factors Affecting Microspore Transformation and Their Regeneration into Green Plants) (i.e. wherein release of the cargo facilitates microspore embryogenesis development).
Regarding claim 54, Brew teaches embryogenesis was induced from the transformed microspores (p. 1,Introduction, ¶2) (i.e. reasonably interpreted as wherein the cargo is an embryogenesis inducing factor).
It would therefore have been obvious to a person of ordinary skill in the art to modify the invention of as taught by Barnett to include the limitations of Lee, Dirks, and Brew to arrive at the instantly claimed method with a reasonable expectation of success because Barnett and Lee teach about introducing molecules or drugs to cell encapsulated within droplets, Lee teaches introducing plasmid DNA into cells encapsulated in droplets and the cells may be plant cells including pollen and microspores, and Dirks and Brew teach methods of introducing plasmid DNA to plant cells to facilitate microspore embryogenesis. Incorporation of the methods taught by Lee, Dirks, and Brew into the method taught by Barnett could be achieved by one of ordinary skill in the art without encountering any special technical obstacles One having ordinary skill in the art would have been motivated to do so for the purpose of producing haploid and double haploid plant embryos as taught by Dirks and Brew (title, abstract).
Conclusion and Inquiries
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA N STOCKDALE whose telephone number is (703)756-5395. The examiner can normally be reached M-F 8:30-5:00 CT.
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JESSICA N. STOCKDALE
Examiner
Art Unit 1663
/JESSICA NICOLE STOCKDALE/Examiner, Art Unit 1663
/CHARLES LOGSDON/Primary Examiner, Art Unit 1662