Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claims 1-25 and 33-37, and 39-41 are pending. Claims 1-19, 25 and 33-36 are withdrawn. Claims 20-24, 37, and 39-41 are examined.
Response to Amendment
Applicant amended claim 24 to replace “first” with “second”, and canceled claim 38.
The rejection of claims 24 and 38 under 35 U.S.C. 112(b) is withdrawn in view of the amendment.
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.
Claims 20-21, 23-24, 37, and 39-41 remain rejected under 35 U.S.C. 103 as being unpatentable over in Zhang (Industrial & Engineering Chemistry Research 57.21 (2018): 7291-7300, hereinafter “Zhang”) in view of Ye (RSC advances 7.77 (2017): 48826-48834).
Regarding claim 20, Zhang teaches a system for producing macroporous alginate beads via cryo-crosslinking under freezing conditions comprising a micro-tube housing an alginate solution (i.e., a micro-dispenser), a tube connected to the microtube on one end and the second end connected to a pump, a first beaker housing a cooled cross-linking reagent and a second beaker housing ethanol under freezing and the cooled cross-linking reagent and configured to receive the frozen drops from the first beaker (Figure 1 of Zhang reproduced below, para 2.3). Zhang teaches the alginate droplets are first generated by the microtube dripping, then these alginate drops are frozen to solid-state beads partially, and then they are cross-linked by the cryo-cross-linking induced by Ca2+ under the freezing conditions (page 7293 left column first para.). In order to address Applicant’s argument, Zhang’s Figure 1 is interpreted as teaching a first beaker that houses a cooled cross-linker solution (i.e., cooled liquid) and receives the drops from the micro-dispenser. The second beaker contains the first beaker and as such the second beaker contains all the contents of the first beaker including the cooled cross-linking reagent and the frozen cross-linked drops.
[AltContent: textbox (Second beaker housing the first beaker and all its contents (i.e., second beaker housing a cooled cross-linking reagent configured to receive the frozen drops from the first beaker))][AltContent: textbox (First beaker housing a cooled cross-linker (i.e. cooled liquid) receiving dispensed droplets from the micro-dispenser to form frozen drops.
the micro-dispenser that themix with cooled liquid to form frozen drops)][AltContent: arrow][AltContent: arrow]
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Zhang does not teach the second end of the tube being affixed to a component that receives pressured air.
However, Ye teaches an air-blast microfluidic nozzle to produce alginate microparticles comprising a microfluidic nozzle housing an alginate solution and a tube connected to the microfluidic nozzle on one end and the second end connected to air compressor with pressured air (Figure 1, para. 2.2). Ye teaches that the pump is
connected to the nozzle with tubes and that the droplets were dropped into a beaker (para. 2.2 first section).
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 the system taught by Zhang by connecting the second end of the tube to a compressor with pressured air, as suggested by Ye. One of ordinary skill in the art would be motivated to do so in order to control the diameter of the droplets. Since Zhang and Ye both teach a desire to form alginate droplets, there is a reasonable expectation of success.
Zhang teaches the alginate bead has an average diameter of 3 mm (Figure 6). Ye teaches the particles have a diameter of 500 µm (i.e., 0.5 mm) (Fig. 3).
Regarding claims 21 and 37, Zhang teaches using 4 g of alginate in 200 mL water (2% alginate solution) (para. 2.2) and teaches that cryo-cross-linking was achieved at -13 °C. Zhang does not teach the pressure in the tube. However, Ye teaches pressure of 40 Kpa (i.e. 0.4 Bar) (para. 3.1.1). One of ordinary skill in the art would be motivated to use an air pressure of 0.4 Bar in order to produce particles with uniform diameter.
Regarding claim 23, Zhang teaches using CaCl2 solution in a low-temperature bath and teaches that cross-linking was achieved at -13oC (page 7293 para. 2.4).
Regarding claim 24, Zhang teaches that the concentration of the cross-linking CaCl2 solution is 15%. One of ordinary skill in the art would be motivated to optimize the concentration of the cross-linking reagent depending on the reagent itself and to control the speed of the cross-linking reaction.
Regarding claim 39, Zhang does not teach the exact size of the pores. However, it can be estimated from Figure 7 that the diameter of the pore in the bead is bigger than 10 µm.
Regarding claim 40-41, Ye teaches alginate bead with pore diameter of 150 µm (Fig. 8d). One of ordinary skill in the art would be motivated to optimize the diameter of the pores in order to form beads capable to holding biological material such as cells of different sizes.
Claim 22 remains rejected under 35 U.S.C. 103 as being unpatentable over Zhang and Ye as applied to claim 20 above, and further in view of Buthe (Journal of microencapsulation 21.8 (2004): 865-876).
Regarding claim 22, Zhang and Ye do not teach wherein the cooled liquid in the first beaker is a hydrophobic solvent, and wherein the hydrophobic solvent is selected from the group consisting of hexane, heptane and octane.
However, Buthe teaches a method for the preparation of alginate beads with improved shape and teaches the alginate solution was dispensed into a solution of hexane (abstract, figure 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 further modify the system taught by Zhang by dispensing the alginate solution into a hexane solution as suggested by Buthe. One of ordinary skill in the art would be motivated to do so in order to improve the roundness of the beads. Since Zhang and Buthe teach a desire to form alginate beads, there is a reasonable expectation of success.
Response to Arguments
Applicant's arguments filed 01/07/2026 have been fully considered but they are not persuasive.
Applicant argues that Zhang does not disclose the features associated with the various beakers. Applicant presents a figure (Remarks page 10) to show what features in Zhang might possibly be the micro-dispenser, the first beaker and the second beaker. Applicant argues the second beaker cannot be the same as the first beaker because the claim delineates between a first beaker and a second beaker and argues the second beaker house a cooled cross-linking reagent configured to receive the frozen drops from the first beaker.
In response to the argument, Zhang teaches a first container housing a cooled crosslinking solution that receives the dispensed droplets (Figure 1) (i.e., a first beaker housing a cooled liquid and configured to receive dispensed droplets from the micro-dispenser). Zhang teaches the droplets in the container freeze first then crosslink (page 7293 left column first para.) (i.e. drops mix with cooled liquid to form frozen drops). Zhang teaches a second beaker housing the first beaker which contains the cooled crosslinking reagent and the frozen droplets (i.e., a second beaker housing a cooled cross-linking reagent). Zhang teaches that the second beaker contains the first beaker and thus can receive the contents of the first container including the frozen droplets (i.e., is configured to receive the frozen drops from the first beaker). Zhang teaches that the drops freeze upon mixing with the cooled solution in the first beaker and then crosslink (i.e. the frozen drops mix unthawed with the crosslinking reagent to form cross-linked drops). Scheme a), presented by Applicant and is identical to the scheme shown in the rejection, reads on the limitations of claim 20.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/MARY A CRUM/Examiner, Art Unit 1657
/THANE UNDERDAHL/Primary Examiner, Art Unit 1699