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 .
Priority
This application is a CONTINUATION of PCT application PCT/EP2022/084841, filed 06/04/2024. Acknowledgement is made of the applicant’s claim for benefit to prior-filed PCT application PCT/EP2022/084841 (filed 12/07/2022), as well as applicant’s claim for foreign priority based on an application DE102021132190.5 filed in Federal Republic of Germany on 12/07/2021. Certified copy of foreign priority is found in file with the document type of “Other reference-patent/Application/Search documents” filed on 09/03/2024.
Election/Restrictions
Applicant’s election without traverse of group I, claims 1-21, 32 and 33 (new added claim), drawn to a method for producing biocompatible structure for the connection and cultivation of biological material (“Linkerspheres”), in the reply filed on 07/31/2026 is acknowledged. Accordingly, claims 1-21, 32 and 33 have been considered on the merits. Claims 22-31 are withdrawn from consideration pursuant 37 CFR 1.142(b).
Claim Objections
Claims 4, 5, 11, 13-15, 19-20 and 32 are objected to because of the following informalities:
Claim 1 recites the steps 1), 2), 3) and 4), while dependent claims including claims 4, 5, 11, 13-15 and 32 recite steps (2), (3) and (4). The steps in the dependent claims need to be replaced with “2)”, “3) and “4)” to keep them consistent with the steps in independent claim 1;
Similarly, claim 13 recites step 5), claims 14 and 15 need to replace the phrase “step (5)” with “step 5)”;
Claims 19 and 20 recite “20 vol.-%” and “5 vol.-%” which are not common expression. They need to be replaced with “20% (v/v)” and “5% (v/v)” to enhance the clarity;
Claim 32 recites “(3)”, since independent claim 1 already has step 3), the step (3) in claim 32 can be step 3’) to differentiate instant step with the step 3) in claim 1.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 14-21 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 subj ect 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 14-16 recite “preferably” renders the claims indefinite. The term "preferably" renders the claim indefinite because it is unclear whether the limitations following the word are part of the claimed invention. See MPEP § 2173.05(d).
Claim 15 recites the limitation " before step (5) " in line 1. There is insufficient antecedent basis for this limitation in the claim. Specifically, claim 15 dependents upon claim 12 and claim 1, neither of the claims refer to step (5).
Claims 17-21 recites the limitation "the isolated and optionally washed and optionally transferred Linkerspheres” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Specifically, claims 17-21 dependent upon claim 13 and claim 1, neither of the claims refer to “optionally washed and optionally transferred Linkerspheres”.
Claim Interpretation
Claims 3-4 recite “a basement membrane-like matrix”. The specification provides the definition: a basement membrane-like matrix is the purified secretion of the murine sarcoma cell line Engelbreth-Holm-Swarm (EHS cells) and resembles in its composition the extracellular matrix of the basement membranes of animal cells (parag 0025). The claims are interpreted in light of such definition in the specification.
Regarding claims 14-16, the claims are interpreted the limitation after the term “preferably” as not required for the claimed invention.
Regarding claim 15, the claim is indefinite. In the interest of compacted prosecution, the claim is interpreted as “after step (4)
Similarly, regarding claims 17-21, the claim is interpreted as “the isolated
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 5-7, 9, 11, 13-17, 21 and 32-33 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Lee et al. (bioRxiv, 2020).
Lee et al. teach a high-throughput oil-in-water droplet microtechnology to generate highly uniform, small-volume, multi-compartment organoids (Abstract).
Regarding claim 1, it is noted that the preamble “for producing biocompatible structures for the connection and cultivation of biological material ("Linkerspheres")” is an intended use. The purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See MPEP 2111.02. Lee et al. teach dropping a liquid solution containing the first extracellular-matrix material (typically recombinant basement membrane (rBM) Matrigel) into mineral oil. The surface tension between water and oil and the resulting Plateau-Rayleigh instability molds the matrix into uniform droplets of spherical shape (p4, parag 1), wherein the cancer cells are enclosed inside an inner compartment composed of rBM Matrigel (see p4, parag 1). Lee et al. teach the method: mix a preset number of cancer cells with 1 μl Matrigel. The mixture was dropped into mineral oil and incubated at 37°C for 30 min to allow for the gelation of Matrigel (p20, parag 1). This teaching reads on the method in instant claim, which includes: 1) Providing a nonpolar, water-immiscible, biocompatible liquid (herein the mineral oil); 2) Introducing a solution of a biocompatible matrix material into the liquid to obtain an emulsion (herein mixture of cells with Matrigel); 3) Incubating the emulsion (at 37°C for 30 min); 4) Forming a three-dimensional structure from the matrix material in the emulsion by incubation to obtain the Linkerspheres (herein gelation of Matrigel). Therefore Lee et al. anticipate instant claim.
Regarding claim 2, following the discussion above, Lee et al. teach the nonpolar, water-immiscible, biocompatible liquid is mineral oil.
Regarding claim 3, following the discussion above, Lee et al. teach the matrix material is Matrigel, which is a basement membrane-like matrix.
Regarding claims 5-7 and 33, Lee et al. teach the mixture (of cancer cells with 1 μl Matrigel) was dropped into mineral oil and incubated at 37°C for 30 min to allow for the gelation of Matrigel (p20, parag 1), reads on that a treatment of the emulsion to solidify the matrix material takes place.
Regarding claim 9, following the discussion above, Lee et al. teach mixing a preset number of cancer cells with 1 μl Matrigel (p20, parag 1), herein the cancer cells are biological cells.
Regarding claim 11, following the discussion above, Lee et al. teach dropping a liquid solution containing the first extracellular-matrix material (typically rBM Matrigel) into mineral oil (p4, parag 1). Moreover, Lee et al. anticipate the method, therefore inherently teach the mixture of cancer cells with 1 μl Matrigel are introduced into the mineral oil as fluid droplets.
Regarding claims 13-14, Lee et al. teach the Matrigel sphere containing the cancer cells was harvested from the mineral oil (p20, parag 1) reads on step 5) in instant claim 13. Moreover, Lee et al. teach the Matrigel sphere containing the cancer cells was harvested from the mineral oil and resuspended in a type I collagen solution (p20, parag 1), since the type I collagen solution is neither Matrigel or mineral oil, under broadest reasonable interpretation (BRI), this step teaches washing the isolated Linkerspheres as recited in instant claim 14.
Regarding claim 15, following the discussion above, Lee et al. teach the Matrigel sphere containing the cancer cells was harvested from the mineral oil and resuspended in a type I collagen solution (p20, parag 1), reads on the step 4’) as recited in instant claim.
Regarding claims 16-17, Lee et al. teach the sphere was collected. Each new organoid was cultured in suspension in a round-bottom well (p20, parag 1). This teaching reads on the isolated Linkerspheres are transferred into a culture vessel as recited in instant claim.
Regarding claim 21, Lee et al. teach figure 2, which has two-compartment organoids containing MDA-MB-231 breast cancer cells after 7 days in culture (p12), reads on the isolated linkerspheres are cultured for at least about 12 hours.
Regarding claim 32, Lee et al. teach the mixture (of cancer cells with 1 μl Matrigel) was dropped into mineral oil and incubated at 37°C for 30 min to allow for the gelation of Matrigel. The Matrigel sphere containing the cancer cells was harvested from the mineral oil and resuspended in a type I collagen solution. This mixture was then dropped into mineral oil at 37 °C for 1 hour to allow for the gelation of type I collagen. The double-layered sphere was then collected. Each new organoid was cultured in suspension in a round-bottom well (p20, parag 1). Herein the step of “the Matrigel sphere containing the cancer cells was harvested from the mineral oil and resuspended in a type I collagen solution” is repeating steps (1) and (2).
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 1-7, 9-11, 13-21 and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Chem. Eng. Sci.238 (2021), published in March 2021, cited in IDS) in view of Lee et al. (bioRxiv, 2020).
Zhang et al. teach a microfluidic droplet templating method that formulates cell-laden Matrigel into intact organoid precursors over the entire processing steps (p1, right column-p2, left column).
Regarding claim 1, it is noted that the preamble “for producing biocompatible structures for the connection and cultivation of biological material ("Linkerspheres")” is an intended use. The purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See MPEP 2111.02. Zhang et al. teach rapid organoid fabrication is started from droplet encapsulation, where cells are suspended in liquid-state extracellular matrix (ECM) and aliquoted into small units, i.e. cell-laden droplets (p2, left column). Specifically, Zhang et al. teach the cells from mouse tissues or human tumors were mixed with growth factor reduced Matrigel and then immediately loaded in a 1 mL syringe and installed in an injection pump at 8 °C. Another injection pump was loaded with a 10 mL injection syringe containing fluorocarbon oil. The two phases were co-injected through PTFE tubing to the third piece of PTFE tubing via a tri-way hand-made PDMS connector (p6, right column). Herein the fluorocarbon oil reads on the “nonpolar, water-immiscible, biocompatible liquid” as recited in instant claim, the growth factor reduced Matrigel reads on the “biocompatible matrix material” in instant claim. Zhang et al. teach the tubing conducting the Matrigel droplets was put into an incubator at 37°C. The Matrigel spheres, gelled from droplets, were injected into a 6-cm culture dish (p6, right column), reads on the step 3) incubating the emulsion and 4) forming a three-dimensional structure from the matrix material in the emulsion by incubation to obtain the Linkerspheres (Matrigel spheres) as recited in instant claim.
Instant claim differs from Zhang et al. is that instant claim introduces the solution of a biocompatible matrix material into the nonpolar, water-immiscible, biocompatible liquid to obtain an emulsion, while Zhang et al. teach co-injecting both biocompatible matrix material and the nonpolar, water-immiscible, biocompatible liquid to the same tubing. However, the limitation of “introduces the solution of a biocompatible matrix material into the nonpolar, water-immiscible, biocompatible liquid to obtain an emulsion” was disclosed by Lee et al. at the time of instant invention.
Lee et al. teach a high-throughput oil-in-water droplet microtechnology to generate highly uniform, small-volume, multi-compartment organoids (Abstract).
Regarding claim 1, Lee et al. teach dropping a liquid solution containing the first extracellular-matrix material (typically rBM Matrigel) into mineral oil. The surface tension between water and oil and the resulting Plateau-Rayleigh instability molds the matrix into uniform droplets of spherical shape (p4, parag 1), wherein the cancer cells are enclosed inside an inner compartment composed of rBM Matrigel (see p4, parag 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhang et al.’s microfluidic droplet templating method which co-injecting both the biocompatible matrix material (which contains cells) and the nonpolar, water-immiscible, biocompatible liquid to a tubing, and directly place the solution of a biocompatible matrix material into the nonpolar, water-immiscible, biocompatible liquid as taught by Lee et al.. The only difference between instant claim and Zhang et al.’s microfluidic droplet templating method is instant claim directly introduces the solution of a biocompatible matrix material (i.e., Matrigel) into the nonpolar, water-immiscible, biocompatible liquid (i.e., mineral oil) to obtain an emulsion. Given that Lee et al. teach the method of dropping a liquid solution containing the first extracellular-matrix material (typically rBM Matrigel) into mineral oil, one of ordinary skill in the art would have substituted Zhang et al.’s microfluidic droplet templating method which co-injecting both biocompatible matrix material (which contains cells) and the nonpolar, water-immiscible, biocompatible liquid to a tubing, and directly drop the biocompatible matrix material (i.e., Matrigel) into the nonpolar, water-immiscible, biocompatible liquid (i.e., mineral oil) according to their research preference. This simple substitution of one known element (directly drop biocompatible matrix material (i.e., Matrigel) into the nonpolar, water-immiscible, biocompatible liquid (i.e., mineral oil)) for another known element (co-inject both biocompatible matrix material (i.e., Matrigel which contains cells) and the nonpolar, water-immiscible, biocompatible liquid (i.e., mineral oil) to a tubing) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Regarding claim 2, following the discussion above, Lee et al. teach dropping a liquid solution containing the first extracellular-matrix material (typically rBM Matrigel) into mineral oil (p4, parag 1).
Regarding claim 3, Zhang et al. teach using growth factor reduced Matrigel (i.e., see p6, right column).
Regarding claims 4-6, following the discussion above, Zhang et al. teach growth-factor reduced Matrigel was used as the ECM, which remained liquid before being sheared into droplets in microfluidics
and was solidified by elevated temperature-triggered physical crosslinking (p2, left column).
Regarding claim 7, following the discussion above, Zhang et al. teach the tubing conducting the Matrigel droplets was put into an incubator at 37 °C (p6, right column).
Regarding claim 9, Zhang et al. teach that cells from mouse tissues or human tumors were mixed with growth factor reduced Matrigel and then immediately loaded in a 1 mL syringe (p116632, right column). The cells from mouse tissues or human tumors are biological cells.
Regarding claim 10, Zhang et al. teach live cells (in the Matrigel) were stained with DAPI (nuclei) and Calcium-AM (cell bodies) (p3, right column).
Regarding claim 11, following the discussion above, Zhang et al. teach droplet encapsulation, where cells are suspended in liquid-state extracellular matrix (ECM) and aliquoted into small units, i.e. cell-laden droplets, and remained liquid before being sheared into droplets in microfluidics (see p2, left column), reads on the matrix material is introduced into the mineral oil as fluid droplets, as recited in instant claim.
Regarding claim 13-14, following the discussion above, Zhang et al. teach Matrigel spheres, gelled from droplets, were injected into a 6-cm culture dish (p6, right column), reads on Isolating the Linkerspheres from the emulsion as recited in instant claim. Moreover, Zhang et al. also teach 6 mL culturing medium was added to each dish (p6, right column), since the culture medium is neither Matrigel or fluorocarbon oil, under broadest reasonable interpretation (BRI), this step teaches washing the isolated Linkerspheres as recited in instant claim 14.
Regarding claim 15, following the discussion above, Zhang et al. teach Matrigel spheres, gelled from droplets, were injected into a 6-cm culture dish. 6 mL culturing medium was added to each dish (p6, right column). Since culture medium is an aqueous solution, this teaching reads on the step 4’) Introducing an aqueous solution, as recited in instant claim.
Regarding claims 16-18 and 20, Zhang et al. teach the Matrigel spheres, gelled from droplets, were injected into a 6-cm culture dish. 6 mL culturing medium was added to each dish. The organoid precursors, i.e. cell-laden Matrigel spheres, were cultured at 37°C in an incubator with 5% CO2 (p6, right column).
Regarding claim 19, following the discussion above, Zhang et al. only teach the concentration of CO2, do not specify the concentration of O2, indicates the concentration of the O2 is the concentration of O2 in the air, which is around 20% (v/v).
Regarding claim 21, following the discussion above, Zhang et al. teach the organoid precursors, i.e. cell-laden Matrigel spheres, were cultured at 37°C in an incubator with 5% CO2, the medium was changed on day 3 and day 7 (p6, right column), reads on the linkerspheres are cultured for at least about 12 hours.
Regarding claim 32, Zhang et al. do not teach after step (2) the following step is carried out: (3) Repeating steps (1) and (2). However, Lee et al. teach the mixture (of cancer cells with 1 μl Matrigel) was dropped into mineral oil and incubated at 37°C for 30 min to allow for the gelation of Matrigel. The Matrigel sphere containing the cancer cells was harvested from the mineral oil and resuspended in a type I collagen solution. This mixture was then dropped into mineral oil at 37 °C for 1 hour to allow for the gelation of type I collagen. The double-layered sphere was then collected. Each new organoid was cultured in suspension in a round-bottom well (p20, parag 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhang et al.’s microfluidic droplet templating method, and repeat the process of mixing a nonpolar, water-immiscible, biocompatible liquid (i.e., a mineral oil) and a solution of a biocompatible matrix material (i.e., an ECM type material) as taught by Lee et al.. The only difference between instant claim and Zhang et al.’s microfluidic droplet templating method is instant claim repeats the process of mixing a nonpolar, water-immiscible, biocompatible liquid (i.e., a mineral oil) and a solution of a biocompatible matrix material (i.e., an ECM type material). Given that Lee et al. teach this process can lead to an organoid model in which cells are enclosed inside an inner compartment (i.e., composed of rBM Matrigel) and an outer compartment (i.e., ECM type I collagen) (see p4, parag 1), one of ordinary skill in the art would have substituted Zhang et al.’s method of obtaining cell-laden Matrigel spheres, and use Lee et al.’s method in order to obtain a sphere having inner compartment and out compartment as needed. This simple substitution of one known element (obtain a sphere having inner compartment and out compartment by repeating process 1) and 2)) for another known element (Zhang et al.’s method of obtaining cell-laden Matrigel spheres) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Regarding claim 33, Zhang et al. teach the tubing conducting the Matrigel droplets was put into an incubator at 37 °C (p6, right column), but not teach the exposure is for about 15 to 30 minutes (to introduce the gelation of Matrigel). However, Lee et al. teach the mixture (of cells with 1 μl Matrigel) was dropped into mineral oil and incubated at 37°C for 30 min to allow for the gelation of Matrigel (p20, parag 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhang et al.’s microfluidic droplet templating method, and incubate the biocompatible matrix material (i.e., Matrigel) at 37 °C for about 30 min as taught by Lee et al.. The only difference between instant claim and Zhang et al.’s microfluidic droplet templating method is instant claim discloses incubate the biocompatible matrix material (i.e., Matrigel) at 37 °C for about 30 min. Given that Lee et al. teach incubating at 37°C for 30 min to allow for the gelation of Matrigel (p20, parag 1), one of ordinary skill in the art would have substituted Zhang et al.’s undisclosed incubation time, and incubate the biocompatible matrix material (i.e., Matrigel) at 37 °C for about 30 min as needed. This simple substitution of one known element (incubating the biocompatible matrix material (i.e., Matrigel) at 37 °C for about 30 min) for another known element (incubating the biocompatible matrix material (i.e., Matrigel) at 37 °C for an undisclosed time) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Claims 1-11, 13-21 and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Chem. Eng. Sci.238 (2021), published in March 2021, cited in IDS) in view of Lee et al. (bioRxiv, 2020), as applied to claims 1-7, 9-11, 13-21 and 32-33, further in view of Chen et al. (Molecules. 2021 Jun 20;26(12):3752).
The teaching of Zhang et al. in view of Lee et al. is set forth above.
Regarding claim 8, Zhang et al. do not teach the solution of the matrix material comprises cell culture medium. However, this was disclosed by Chen et al. at the time of instant invention.
Chen et al. review recent developments in crosslinking polymers or monomers in microfluidic chips for the purpose of producing both matrix-type and core-shell microgels (p2, parag 3).
Regarding claim 8, Chen et al. teach a powdered crosslinking medium, such as dehydraed cell culture medium, can be dispersed in a carrier oil and used for on-chip crosslinking (p5, parag 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhang et al.’s microfluidic droplet templating method which mixing cells with growth factor reduced Matrigel, and use powdered crosslinking medium such as dehydraed cell culture medium as taught by Chen et al.. The only difference between instant claim and Zhang et al.’s microfluidic droplet templating method is instant claim has the solution of the matrix material comprises cell culture medium. Given that Chen et al. teach a powdered crosslinking medium such as dehydraed cell culture medium can be dispersed in a carrier oil and used for on-chip crosslinking (p5, parag 1), one of ordinary skill in the art would have substituted Zhang et al.’s Matrigel, and use a dehydraed cell culture medium for the crosslinking and gelation according to their research interest. This simple substitution of one known element (using a powdered crosslinking medium such as dehydraed cell culture medium for cell culture) for another known element (using a matrix material comprises Matrigel for cell culture) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Claims 1-7, 9-21 and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Chem. Eng. Sci.238 (2021), published in March 2021, cited in IDS) in view of Lee et al. (bioRxiv, 2020), as applied to claims 1-7, 9-11, 13-21 and 32-33 above, further in view of Sinha et al. (J Vis Exp. 2019 Feb 11;(144)).
The teaching of Zhang et al. in view of Lee et al. is set forth above.
Regarding claim 12, Zhang et al. teach using syringe and injection pump, do not teach the introduction of the solution into the mineral oil as fluid droplets takes place via a pipette tip. However, this was disclosed by Sinha et al. at the time of instant invention.
Sinha et al. teach a new methodology that uses pipette-tips to load cells to droplet-based microfluidic devices without the significant loss of cells (p1, Abstract).
Regarding claim 12, Sinha et al. teach using tip-loading for aqueous droplet (Protocol 2.2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhang et al.’s microfluidic droplet templating method which co-injecting both biocompatible matrix material (which contains cells) and the nonpolar, water-immiscible, biocompatible liquid by syringe and injection pump to a tubing, and use a pipette tip to load the cell mixture as taught by Lee et al.. The only difference between instant claim and Zhang et al.’s microfluidic droplet templating method is instant claim uses a pipette tip for the introduction of the solution into the mineral oil as fluid droplets. Given that Sinha et al. teach pipette tip-loading for aqueous droplet, one of ordinary skill in the art would have substituted Zhang et al.’s method of loading the biocompatible matrix material (which contains cells) by syringe and injection pump, and use pipette tip for the process according to their research preference. This simple substitution of one known element (using pipette tip for loading biocompatible matrix material which contains cells) for another known element (using syringe and injection pump for loading biocompatible matrix material which contains cells) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Conclusion
No claims are allowed.
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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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