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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/28/24 is being considered by the examiner.
Claim Status
Claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, 18, 19, 20, and 21 are pending and are examined. Claims 16 and 22 are cancelled.
Claim Objections
Claim 1 is objected to because of the following informalities: Correct “between 5 to 45 mL” to “between 5 mL to 45 mL”. Appropriate correction is required.
Claim 7 is objected to because of the following informalities: Add punctuation “.” at the end. Appropriate correction 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, 2, 4, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, 18, 19, 20, and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Song (US Pub 2018/0334646).
Regarding Claim 1, Song teaches a bioreactor for the production of organoids (cell culture systems and methods of generating organoids. See Abstract.), the bioreactor comprising:
is comprised of at least two reactor modules for cultivation of said organoids (culture wells in base substrate 70),
wherein the at least two reactor modules are comprised of a culture vessel having a volume of between 5 to 45 mL (volume would be capable of being between 5 to 45 ml), and
wherein each reactor module further comprises; at least one gas exchange portal for continues gas exchange to and from the reactor module ([0045] Similar to the standard plate cover, while ensuring gas exchange from the side, SpinΩ's plate cover design contains no direct vertical opening to the outside and prevents contaminants from falling into wells.)
a stirring element inside the reactor module for providing continuous mixing ([0051] Generate flow and lift: the key function of SpinΩ is provided by the spin shafts with fins on the side. The spin generates circular laminar flow within the wells. The fins are slightly tilted to generate a lifting force to ensure tissue culture constantly in suspension. The fins are for mixing (stirring).),
a motor in operable connection with the stirring element (motor 30), and
a lid or cap closing the bioreactor as a culture vessel (plate cover 50),
wherein the bioreactor further comprises a microcontroller in communication with said motor of each reactor module for controlling the speed of the stirring element per reactor module ([0086] A control system such as a computer or other automation devices (not shown in the figures) may be used to monitor and control the operation of the device, and to analyze obtained data).
Regarding Claim 2, Song teaches the bioreactor according to claim 1, wherein the bioreactor is further comprised of one or more holders arranged for holding the at least two reactor modules (base substrate 70).
Regarding Claim 4, Song teaches the bioreactor according to claim 1, wherein the at least two reactor modules are at least 4 reactor modules (See Fig. 1, culture wells in base substrate 70).
Regarding Claim 7, Song teaches the bioreactor according to claim 6, wherein the multitude of fins or fin structures is at least three fins or fin structures, along the length of the stirring element ([0046] Below the plate cover 50, the spin is generated by one or more paddles or fins 65 attached on each shaft 60.)
Regarding Claim 8, Song teaches the bioreactor according to claim 1, wherein the at least two reactor modules are further comprised of one or more sensors selected from the group consisting of temperature, gas and pH sensor ([0086] sensors may be connected to the control system using electrodes and may be used to simultaneously measure the concentration of oxygen and the pH value in the culture spaces. Further, with multiple sensors, the gradient of a given material in the chamber can be measured. Feedback information may include values of pH, glucose and oxygen concentrations, temperature, osmolarity, shear forces, and the like.).
Regarding Claim 9, Song teaches the bioreactor according to claim 1, wherein the bioreactor further comprises one or more elements selected from the group consisting of control panel, LCD screen, power source ([0087] Electrical conductors may be embedded in the device for connecting sensor and pump electrodes to external electronics and power sources.).
Regarding Claim 10, Song teaches a method for cell culturing using the bioreactor according to claim 1, wherein the cell culturing is done at a cell culture volume of between 5 to 45 mL ([0172] a 15 ml conical tube).
Regarding Claim 11, Song teaches the method according to claim 10, wherein the cell culturing is one or more selected from the group consisting of the cultivation of an organoid, immune cells, antibodies, stem cells, EBs, iPSCs, ESCs, and spheroids or cellular aggregates ([0097] Here, we developed a miniaturized spinning bioreactor (SpinΩ as shown in FIGS. 1-11) to generate forebrain-specific organoids from human iPSCs.).
Regarding Claim 12, Song teaches the method according to claim 11, wherein the organoids are human organoids ([0097] Here, we developed a miniaturized spinning bioreactor (SpinΩ as shown in FIGS. 1-11) to generate forebrain-specific organoids from human iPSCs.).
Regarding Claim 13, Song teaches the method according to claim 11, wherein the organoid is one or more selected from the group consisting of liver, intestine, kidney, pancreas, lung, brain, spleen and heart organoid ([0068] kidney).
Regarding Claim 14, Song teaches a method for expansion and/or differentiation of organoids, the method comprising
the steps of a) providing the bioreactor according to claim 1
b) providing culture media and cells for the production of the organoids in the two or more reactor modules (Fig. 1, reactor modules on base substrate 70. [0013] the invention provides a method of screening an agent. The method includes providing a cell culture system of the present invention, culturing cells in a culture well in culture media under conditions suitable for cell culture, wherein the conditions comprise mixing of the cell culture via actuation of the motor, and introducing a biological agent into the culture media and detecting a cellular response, thereby screening the agent.),
c) culturing of the cells under culturing conditions suitable for organoid cultivation, mixing the cell culture by activating the motor of the two or more reactor modules, setting the rotational speed per reactor module between 40 to 120 rpm ([0052] The speed of the spin shaft is tunable from 30-125 RPM, to ensure full suspension and flow of human iPSC-derived brain organoids from 200 micrometers to 3 millimeters in diameter.), and
d) harvesting of the organoids from the one or more reactor modules (harvesting organoids from the culture well, thereby producing organoids.).
Regarding Claim 15, Song teaches the method according to claim 14, wherein the culture media and cells in step b at the start of cell cultivation have a cell culture volume of between 5 to 15 mL (SpinΩ requires as little as 2 mL of media to support tissues growth, dramatically reducing the cost for maintaining tissue culture.), and/or wherein culturing of the cells for organoid cultivation is done at a cell culture volume of between 5 to 45 mL ([0216] On day two, primary seed cultures were inoculated in two 16 mL of SC-URA media).
Regarding Claim 17, Song teaches the method according to claim 14, wherein culturing of the cells for organoid cultivation is done for at least 10 days ([0079] The cells may be cultured for any duration of time appropriate for forming a particular tissue structure. In embodiments, cells are culture from about 2 to 100 days, for example, between about 3 to 80 days, 4 to 21 days or 5 to 14 days.), providing an average cell expansion of at least 20 fold ([0149] For example, embryoid bodies of around 300 mm in diameter could expand to organoids that are up to 3 mm in diameter, achieving a 1,000-fold expansion in cell mass.).
Regarding Claim 18, Song teaches the method according to claim 14, wherein the rotational speed in the two or more reactor modules is between 40 to 120 rpm; preferably 50 to 80 rpm, more preferably 55 to 70 rpm, most preferably 60 to 65 rpm ([0052] The speed of the spin shaft is tunable from 30-125 RPM, to ensure full suspension and flow of human iPSC-derived brain organoids from 200 micrometers to 3 millimeters in diameter.).
Regarding Claim 19, Song teaches the method according to claim 14, wherein the rotational speed differs between the two or more reactor modules [0141] Many of the design parameters of SpinΩ, including number and size of wells, rotation speed, shaft angle, and shape, can be customized based on specific needs.).
Regarding Claim 20, Song teaches the method according to claim 14, wherein the organoid is one or more selected from the group consisting of liver, intestine, kidney, pancreas, lung, brain, spleen and heart organoid, preferably liver organoid ([0068] kidney).
Regarding Claim 21, Song teaches the method according to claim 14, wherein the organoid is a liver organoid, and the rotational speed is between about 50 to 80 rpm, and/or wherein the organoid is an intestinal organoid and the rotational speed is between about 80 to 120 rpm ([0052] The speed of the spin shaft is tunable from 30-125 RPM, to ensure full suspension and flow of human iPSC-derived brain organoids from 200 micrometers to 3 millimeters in diameter. [0068] liver [0098] intestinal).
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 3, 5, and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Song (US Pub 2018/0334646).
Regarding Claim 3, Song teaches the bioreactor according to claim 2.
Song is silent to the holder is arranged to hold at most four reactor modules.
Song teaches Fig. 1 which shows reactor modules in the base substrate 70. There are 12 reactor modules shown.
However, Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have re-arranged the device of Song to hold at most four reactor modules to allow for a more compact and portable device.
Regarding Claim 5, Song teaches the bioreactor according to claim 1.
Song is silent to the stirring element is a stirring rod having a length corresponding to at least 80%, more preferably at least 90% of the total length of the culture vessel of the reactor module.
Song teaches fins, see Fig. 2F which act as a stirring element. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted a stirring rod for the fins in the device of Song to allow for an alternative configuration and for the stirring rod having a length corresponding to at least 80%, more preferably at least 90% of the total length of the culture vessel of the reactor module to achieve maximum mixing.
Regarding Claim 6, Song teaches the bioreactor according to claim 1, wherein the stirring element comprises a multitude of fins or fin structures along the length of the stirring element ([0046] Below the plate cover 50, the spin is generated by one or more paddles or fins 65 attached on each shaft 60.),
Song is silent to along the length of the stirring element said fins or fin structures are separated by a space of 1 to 30mm.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have re-arranged the along the length of the stirring element said fins or fin structures are separated by a space of 1 to 30mm to minimize the number of fins required along the reactor module.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACQUELINE BRAZIN whose telephone number is (571)270-1457. The examiner can normally be reached M-F 8-5.
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/JB/
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
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