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 .
Claims 1-11, 21-23, and 25 are pending.
Claims 1 and 2 have been amended.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/06/2026 has been entered.
Response to Arguments
Applicant’s arguments dated 1/6/2026 with respect to claim(s) 1-11, 21-21, and 25 have been considered, and are persuasive in regards to the additional new features that have been added. It is noted though from the new search and consideration conducted in light of the additional features that a new rejection of the claims are shown below. The rejections were made with new references that address the additional features, particularly in light of the teachings of WALSH and KIM.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Heyes (US 2016/0151284 A1) in view of KIM (US 2018/0133672 A1) and WALSH (US 2016/0235688 A1).
In the HEYES reference concerning the concept of the process of continuous mixing, wherein, it forms liposome encapsulating the nucleic acid (mRNA), see [0227]. Wherein, the there is a lipid particles that are provided in a solution. The concept hereof a mixing environment is noted of the solutions is thus known, see [0227, 0228].
Wherein, Re: Claim 1, Heyes teaches of a process of encapsulating in liposomes comprising:
a. providing a first solution (see with nucleic acid, mRNA, see [0227]),
b. providing a second solution (see lipid solution, see [0227], and
c. mixing the first and the second solutions to form encapsulated liposomes (see [0227, 0228]), the rate can be controlled (see teaching of the continuous process, see [0229]).
Whereby, HEYES does not specifically teach of the first and second stream that are provided into the mixing for the process, nor of a pumpless process for the streams, and of the process results in encapsulation efficiency of at least 75%.
Regarding the concept of using pumpless system for the flow, KIM teaches of forming microspheres formed via mixing of material flows, see first and second material reservoir 300, 400, through mixing or encapsulation, see [0271]. See also formation of microsphere, at A, see Fig. 1, see also Fig. 5, of the flows that meet. Wherein, the controlled flows from the reservoirs can be conducted with general constant flow rate via gravity force, see claim 26 of KIM. Whereby, the concept for a pump free transport of the liquids from the reservoir and to mix are known in the mixing arts as seen in KIM.
It would have been obvious for one of ordinary skill in the art to have modified HEYES with the streams and a pumpless system such as use of gravity force as taught by KIM as a known alternative method of the system for encapsulation of the materials. See under KSR rationale, MPEP 2143, as it seen as combining prior art elements according to known methods to yield predictable results.
Regarding the encapsulation ratio, WALSH teaches of mixing that can be done via microfluidic mixer, including herringbone mixer, zig-zag mixer, or macroscopic mixer, including T-mixer, Y-mixer, or W-mixer, [0068, 0098], and further, of teaching of rapid mixing can affect the encapsulation efficiency, see [0118], the encapsulation efficiency being from 60-100%, [0130], wherein, the teaching [005-0026] concerns of the flow and mixing of the streams, and silent on how the flows are formed of the streams.
It would have been obvious for one of ordinary skill in the art to have further modify the system of the modified HEYES with the known encapsulation efficiency as taught by WALSH with the mixing of the streams, see under KSR rationale, MPEP 2143, as use of known technique to improve similar devices (methods or products) in the same way.
Re: Claim 2, the modified HEYES reference teaches of a process of encapsulating in liposomes, it is noted that the modified HEYES reference fails to teach: step “d. wherein each of steps a-c is performed under gravity feed and without external pressure.”
Wherein, this is seen as a gravity feed of the streams into the mixing container. Wherein, the HEYES reference does not specifically teach of gravity feed.
Regarding the concept of using pumpless system for the flow, KIM teaches of forming microspheres formed via mixing of material flows, see first and second material reservoir 300, 400, through mixing or encapsulation, see [0271]. See also formation of microsphere, at A, see Fig. 1, see also Fig. 5, of the flows that meet. Wherein, the controlled flows from the reservoirs can be conducted with general constant flow rate via gravity force, see claim 26 of KIM.
It would have been obvious for one of ordinary skill in the art to have modified HEYES with the streams and a pumpless system such as use of gravity force as taught by KIM as a known alternative method of the system for encapsulation of the materials. See under KSR rationale, MPEP 2143, as it seen as combining prior art elements according to known methods to yield predictable results.
The references do not specifically teach of the encapsulation efficiency of at least 75%.
Regarding the encapsulation ratio, WALSH teaches of mixing that can be done via microfluidic mixer, including herringbone mixer, zig-zag mixer, or macroscopic mixer, including T-mixer, Y-mixer, or W-mixer, [0068, 0098], and further, of teaching of rapid mixing can affect the encapsulation efficiency, see [0118], the encapsulation efficiency being from 60-100%, [0130], wherein, the teaching [005-0026] concerns of the flow and mixing of the streams, and silent on how the flows are formed of the streams.
It would have been obvious for one of ordinary skill in the art to have further modify the system of the modified HEYES with the known encapsulation efficiency as taught by WALSH with the mixing of the streams, see under KSR rationale, MPEP 2143, as use of known technique to improve similar devices (methods or products) in the same way.
Re: 3 (upon 1), wherein the first stream is provided by a first conduit; and the second stream is provided by a second conduit, and thereby mixing the mRNA solution and the lipid solution. See teaching by WALSH of the first and second streams that meet together for mixing, wherein, this encompasses the claimed conduits.
Whereby, it would have been obvious for one of ordinary skill in the art to recognize the modified Heyes reference with the conduits of WALSH for providing the flow of the materials for mixing.
Re: 4 (upon 3), wherein the junction comprises a T connector or a Y connector. See teaching by WALSH of both T-shaped and Y-shaped junction for mixing.
See also KIM of the flows/channels 11, 12, 13 that flow to meet at a junction 15, see Fig. 5.
Re: 5 (upon 3), wherein the first conduit is connected to a first reservoir containing the mRNA solution and the second conduit is connected to a second reservoir containing the lipid solution.
See teaching by KIM of the input 1 and input n which connect to the mixer, see Fig. 1.
See teaching by WALSH of the first source material reservoir and second source material reservoir, see [0178], Fig. 14.
Claim(s) 6-11, 21-23, and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over the modified HEYES as applied to claim 1 above, and further in view of EP1203614A1 (see IDS, and also machine translation of document via Google Patents).
Re: 6 (upon 1), wherein a first constriction controls the first controlled flow rate and a second constriction controls the second controlled flow rate.
HEYES does not specifically teach constrictions for the controlled flow rates.
See the teaching of the mixing ratio that can be controlled via the pressure, the increasing of the diameter of the opening 3, and flows, see page 6 of translated EP reference, lines 1-10. The EP reference of a device for producing lipid vesicles, which comprises the following components: a pipe (1) which is hollow in the interior and is intended for transporting a polar liquid phase, a pipe (2) which is hollow in the interior and is intended for transporting a lipid-containing organic liquid phase, a collecting container (7) for receiving lipid vesicles produced, and means for transporting the liquid phases through the pipes (1) and (2), characterized in that the pipe (1) is connected to the pipe (2) via a common, liquid-permeable orifice (3), the common orifice (3) being arranged so that the organic liquid phase from the pipe (2) can pass through the orifice (3) substantially perpendicularly to the direction of flow of the polar liquid phase flowing in pipe (1) and can enter, preferably in the form of a spray mist, the polar liquid phase flowing past the orifice (3),and furthermore the pipes (1) and (2) in the region of the common orifice (3) being free of means generating turbulences or shear forces.
Wherein, in EP1203614A1 teaches of a process of encapsulating comprising:
a. providing a first stream (see pipe 1) comprising a solution at a first controlled flow rate,
b. providing a second stream (see pipe 2) comprising a solution at a second controlled flow rate, and
c. mixing the first stream and the second stream to form encapsulation (see wherein the pipe 1 is connected to pipe 2, and via orifice 3), wherein the first controlled flow rate and the second controlled flow rate are achieved without use of a pump. See page 5 of the EP reference:
“The volumes and flow velocities of the lipid-containing and polar phases should preferably be coordinated with one another in such a way that unused excesses of one of the two phases are largely avoided. The lipid-containing phase is pumped from a second reservoir 8 with a pump 9 through a filter 10 and a check valve or other pressure-blocking valve into an intermediate container 11. In this example, the intermediate container 11 is connected via an interposed filter 12 to a pressure source 13, for example a pressure container which preferably contains an inert gas, for example nitrogen gas, under pressure and with the aid of which the lipid-containing phase from the intermediate container 11 via a controllable valve in the direction of the crossflow module 4 is pressed. If no oxidation protection is necessary due to the lipid composition and / or the choice of the liposomal substance to be enclosed, compressed air can also be used. Alternatively, the lipid-containing phase can be conveyed from the intermediate container 11 via the line 2 to the crossflow module 4 by means of a pump. As soon as the polar phase passes opening 3 in cross-flow module 4, a controllable valve in line 2 is opened and the lipid-containing phase is pressed or pumped through opening 3 into line 1 and thus into the polar phase. A sampling device14 can also be provided downstream of the cross-flow module 4 for process and quality control.”; and
furthermore, claim 10 of the reference teaches for a pump-free:
“Device according to one of claims 1-8, characterized in that the means for conveying the liquid phases comprise a pressure source (13) which is connected to an intermediate container (11), optionally via an intermediate filter (12), and which by means of pressure overlay by Compressed air or an inert gas under pressure enables pump-free conveyance of the lipid-containing phase from the intermediate container (11) via the line (2) through the opening (3).”
Wherein, it would have been obvious for one of ordinary skill in the art to have modified the HEYES reference with the EP reference regarding the manner flow control of the streams for mixing of the solutions together. As under KSR, see MPEP 2143, this is seen as combining prior art elements according to known methods to yield predictable results.
Re: 7 (upon 6), wherein the first constriction and second constriction provide controlled flow rates that are the same. See controllable valves, check valve that can control the volumes and flow velocities, see page 5 of translation of EP document.
Re: 8 (upon 6), wherein the first constriction and the second constriction provide controlled flow rates that are different. Wherein, the teaching of the ratios being changed via the diameter change and flow in the EP document.
Re: 9 (upon 8), wherein the first controlled flow rate to second control flow rate is at a ratio of about 1.2X, 1.5X, 1.8X, 2.0X, 2.5X, by 1.2X or greater, 1.5X or greater, 1.8X or greater, 2.OX or greater, 2.5X or greater. See differences in the flow rates in the examples of the EP document.
Re: 10 (upon 8), wherein the second controlled flow rate to first control flow rate is at a ratio of about 1.2X, 1.5X, 1.8X, 2.0X, 2.5X, by 1.2X or greater, 1.5X or greater, 1 .8X or greater, 2.OX or greater, 2.5X or greater. See differences in the flow rates in the examples of the EP document.
Re: 11 (upon 6), wherein the first constriction comprises a first diameter of the first conduit and the second constriction comprises a second diameter of the second conduit. See teaching of the different diameters in the examples of the EP document.
Re: 21 (upon 11), wherein the first diameter of the first conduit is selected from the following ranges: 0.1 mm -1 mm, 1mm -100 mm, 100 mm -1 cm, 1 cm - 100 cm. conduit is selected from the following ranges: 0.1 mm -1 mm, 1 mm-100 mm, 100 mm - 1 cm, 1 cm - 100 cm. See in the EP reference, examples of translated document that can include 10 mm, 6 mm.
Re: 22 (upon 11), wherein the second diameter of the second conduit is selected from the following ranges: 0.1 mm -1 mm, 1mm -100 mm, 100 mm - 1 cm, 1 cm - 100 cm. See teaching in the EP reference, on page 7 of translated document of hose having a 1.6 mm inside diameter for the flow of the ethanol for the lipid phase.
Re: 23 (upon 6), wherein the first controlled flow rate ranges from about 0.1-1 mL/min, 1-150 mL/min, 150-250 mL/min, 250-500 mL/min,500-1000 mL/min, 1000-2000 mL/min, 2000-3000 mL/min, 3000-4000 mL/min, or 4000-5000 mL/min. See teaching in the EP reference, example 6: 2700 mL/min; example 7: 400 mL/min; example 8: 2700 mL/min; example 9: 400 mL/min, see page 7 of translated EP document.
Re: 25 (upon 6), wherein the second controlled flow rate ranges from about 0.1-1 mL/min, 1-150 mL/min, 150-250 mL/min, 250-500 mL/min,500-1000 mL/min, 1000-2000 mL/min, 2000-3000 mL/min, 3000-4000 mL/min, or 4000-5000 mL/min. See teaching in the EP reference, example 6: 75 mL/min; example 8: 67 mL/min
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. See attached PTO-892 form, most teaches of either gravity feed or of encapsulation efficiency from mixing in the art.
DEROSA (US 2016/0038432 A1) of encapsulation with efficiency teaching of over 70%, see [0014, 0015], and see teaching flow pumps of the materials, see Figures.
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/EMMANUEL S LUK/Primary Examiner, Art Unit 1744