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
The instant application is a national stage entry of PCT application PCT/US2022/054220, filed 06/24/2024 under 35 USC 371. Acknowledgement is made of the applicant’s claim for benefit to prior-filed U.S. provisional patent applications 63/296,224 (filed 01/04/2022), as well as the applicant’s claim for foreign priority based on an application EP22159731.3 filed in Europe on 03/02/2022.
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 1-16 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 subject 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.
Claim 1 recites the limitation "automatable" in line 2. There is insufficient antecedent basis for this limitation in the claim. Applicant may amend instant claim to recite “automated” to obviate the rejection.
Claims 2-11 depend from claim 1 directly or indirectly, and thus inherit the deficiency and are rejected on the same basis.
Claim 5 recites “preferably” renders instant claim indefinite. The term "preferably" renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 9, 10, 12 and 13 recite “at least a portion of” renders instant claims indefinite. The phrase “at least a portion of” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In instant case, it is unclear how much (i.e., the percentage) is counted as “a portion of” the cells, the non-precipitated liquid mixture as well as the filtrate.
Claims 14-16 depend from claim 12 directly or indirectly, and thus inherit the deficiency and are rejected on the same basis.
Claim Interpretation
As stated above, claim 5 is indefinite due to using the term “preferably”. In giving the claims their broadest reasonable interpretation, the examiner has interpreted the limitation as not required for the claimed invention.
Regarding claims 9, 10, 12 and 13, the recitations of “at least a portion of” of the cells, the non-precipitated liquid mixture as well as the filtrate are interpreted as comprising any amount (i.e., the percentage) of the cells, the non-precipitated liquid mixture as well as the filtrate.
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 1-4 and 6 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Johnson et al. (WO 2004/058046 A2, as cited in IDS).
Johnson et al. teach treatment apparatus, system and method for treating a biological fluid, such as blood or blood components (Abstract).
Regarding claim 1, Johnson et al. teach red cell (RBCs) or other biological fluid treatment processes (parag 000122, also figure 1). Johnson et al. teach a disposable pre-assembled fluid circuit module is provided for use with a reusable control unit for treating red cells in accordance with a predetermined sequence. The disposable module may include a fluid inlet, a red cell (or other biological fluid) inlet, a fluid outlet, an interior chamber containing a red cell treating agent, an access member for accessing the interior chamber, a fluid pump and a flow path interconnecting the fluid inlet, red cell inlet, fluid outlet, pump and access member to provide fluid flow through the module in accordance with the predetermined sequence, under the control of the reusable control unit (parag 00018). The concentrated red cells and first solution are combined with the reconstituted pathogen inactivation agent and optional quenching agent (parag 000125). The combined solutions may be mixed by expressing the solutions back and forth between two separate containers or bags, or between two or more compartments of the same container or bag. This can be done manually or can be done in an automated fashion by apparatus that alternately compresses and releases the containers or container portions to alternately express the solution back and forth between the containers or container compartments (parag 00170). This teaching reads on the same method as recited in instant claim, which is an automated method comprising mixing red cells (herein RBCs) and a red cell treating agent (herein pathogen inactivation agent and optional quenching agent) in a mixing chamber, and mixing the cells and chemical by back-and-forth liquid flow in the mixing chamber.
Regarding claim 2, following the discussion above, Johnson et al. teach i.e., in figure 67, the output bag includes a draw tube 522 which extends into the bag and near the lower end of the bag, to draw the combined red blood cell concentrate and pathogen inactivation fluid from the bag and recirculate it into the red blood cell line leading from the red blood cell container 510 to flow junction 514 (parag 303), the mixing chamber (herein the bag) is broader than the tube.
Regarding claims 3 and 4, following the discussion above, Johnson et al. teach the flow rate of the pathogen inactivation chemical may be controlled by a peristaltic pump or by an actuator that progressively depresses the plunger of a syringe pump in a programmed and controllable fashion to accurately achieve the desired linear flow rate of pathogen inactivation fluid for mixing with the red blood cells flowing through the first fluid path (parag 000296). Johnson et al. teach the concentrated red blood cells are withdrawn from the container in which they have been stored at a relatively precisely controlled flow rate. The reconstituted inactivation agent and quenching agent are added to the red
cell flow stream also at a relatively precisely controlled flow rate, so that the ratio of the flow rate of the
reconstituted inactivation agent and quenching agent (with the second part of the solution) and the flow rate of the collected red blood cells is basically constant (parag 000161). The combined solutions may
be mixed by expressing the solutions back and forth between two separate containers or bags, or between two or more compartments of the same container or bag (parag 000170).
Regarding claim 6, Johnson et al. teach figure 1 process flow chat, wherein RBCs are stored in suspension solution, this reads on the RBCs are provided in form of a cell suspension.
Claims 1 and 3-11 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Suh et al. (US 9,328,342 B2, patented in 2016, as cited in IDS).
Suh et al. teach isolating extrachromosomal replicons such as plasmids (Abstract).
Regarding claim 1, Suh et al. teach a method of breaking open cells in a liquid culture and capturing plasmid DNA on a pipette tip column (Col 2, L41-43). The method involves the following steps:
1. cell growth; 2. cell lysis; 3. precipitation of cell debris and other components; 4. capture of plasmid DNA on a pipette tip column; 5. elution of the purified plasmid. All the method steps can be performed using automation in a 96-well format or another microplate format (e.g., 6, 12, 24, 48, 72 or 384 wells). Steps 1 through 3 can be performed using a single plate (Col 2, L48-57). Lysis buffer comprised of sodium hydroxide and SDS is on the robotic instrument. A gentle mixing step follows the addition of the lysis buffer (Col 5, L47-50). In Example 2, the detailed step about the mixing is described: mix using gentle pipette mixing with wide bore 1000 μL pipette tips for 30 back-and-forth cycles of 1 mL/min (Col 16, L16-18). This teaching reads on the automated method as recited in instant claim.
Regarding claims 3 and 4, following the discussion above, the back-and-forth liquid flow cycles are aspirate and expel steps (cycles) by pipette, which worked as same physical principles as a pump. Therefore under broadest reasonable interpretation (BRI), the back-and-forth liquid flow is provided by injecting liquid (as recited in instant claim 3) and ejecting liquid (as recited in instant claim 4), wherein the pipette (pump) is connected to the mixing chamber (i.e., a mixing well) to execute such operation.
Regarding claim 5, Suh et al. teach in Example 2, the detailed step about the mixing is described: mix using gentle pipette mixing with wide bore 1000 μL pipette tips for 30 back-and-forth cycles of 1 mL/min (Col 16, L16-18).
Regarding claim 6, Suh et al. teach in Example 3, plasmid purification from E. coli, cultures were collected into microcentrifuge tubes. These tubes were centrifuged at 10,000 RPM for 10 minutes using a microcentrifuge. Supernatant was removed from the pelleted cells. Pelleted cells from the 150 μL cultures were resuspended in 150 μL of resuspension buffer (Col 18, L1-6). These cell suspensions are used for the purification, which using lysis buffer and mixing (see Col 18). These resuspended cells are the cells provided in form of a cell suspension.
Regarding claim 7, following the discussion above, Suh et al. teach using lysis buffer comprised of sodium hydroxide and SDS (Col 5, L47-48).
Regarding claim 8, Suh et al. teach lysis can be performed after the addition of RNase or
concurrently (Col 5, L28-29).
Regarding claims 9 and 10, Suh et al. teach after the lysis step, the genomic DNA is released into the solution (Col 21, L25-26), indicates that at least some cells in the liquid mixture undergoes lysis as recited in instant claim 9 and DNA (a macromolecule) is released as recited in instant claim 10.
Regarding claim 11, following the discussion of claim 1, Suh et al. also teach precipitation step, which using precipitation buffer (Col 6, L13). After addition of the precipitation buffer, gentle mixing is performed by repeated aspiration and expulsion of the mixture (Col 6, L56-58).
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, 3-13 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Suh et al. (US 9,328,342 B2, patented in 2016, as cited in IDS) in view of Chen (WO 2009/111336 A2), as evidenced by Takara Bio USA, Inc (User manual, 2019).
Suh et al. teach isolating extrachromosomal replicons such as plasmids (Abstract).
Regarding claim 1, Suh et al. teach a method of breaking open cells in a liquid culture and capturing plasmid DNA on a pipette tip column (Col 2, L41-43). The method involves the following steps:
1. cell growth; 2. cell lysis; 3. precipitation of cell debris and other components; 4. capture of plasmid DNA on a pipette tip column; 5. elution of the purified plasmid. All the method steps can be performed using automation in a 96-well format or another microplate format (e.g., 6, 12, 24, 48, 72 or 384 wells). Steps 1 through 3 can be performed using a single plate (Col 2, L48-57). Lysis buffer comprised of sodium hydroxide and SDS is on the robotic instrument. A gentle mixing step follows the addition of the lysis buffer (Col 5, L47-50). In Example 2, the detailed step about the mixing is described: mix using gentle pipette mixing with wide bore 1000 μL pipette tips for 30 back-and-forth cycles of 1 mL/min (Col 16, L16-18). This teaching reads on the automated method as recited in instant claim.
Regarding claims 3 and 4, following the discussion above, the back-and-forth liquid flow cycles are aspirate and expel steps (cycles) by pipette, which worked as same physical principles as a pump. Therefore under broadest reasonable interpretation (BRI), the back-and-forth liquid flow is provided by injecting liquid (as recited in instant claim 3) and ejecting liquid (as recited in instant claim 4), wherein the pipette (pump) is connected to the mixing chamber (i.e., a mixing well) to execute such operation.
Regarding claim 5, Suh et al. teach in Example 2, the detailed step about the mixing is described: mix using gentle pipette mixing with wide bore 1000 μL pipette tips for 30 back-and-forth cycles of 1 mL/min (Col 16, L16-18).
Regarding claim 6, Suh et al. teach in Example 3, plasmid purification from E. coli, cultures were collected into microcentrifuge tubes. These tubes were centrifuged at 10,000 RPM for 10 minutes using a microcentrifuge. Supernatant was removed from the pelleted cells. Pelleted cells from the 150 μL cultures were resuspended in 150 μL of resuspension buffer (Col 18, L1-6). These cell suspensions are used for the purification, which using lysis buffer and mixing (see Col 18). These resuspended cells are the cells provided in form of a cell suspension.
Regarding claim 7, following the discussion above, Suh et al. teach using lysis buffer comprised of sodium hydroxide and SDS (Col 5, L47-48).
Regarding claim 8, Suh et al. teach lysis can be performed after the addition of RNase or
concurrently (Col 5, L28-29).
Regarding claims 9 and 10, Suh et al. teach after the lysis step, the genomic DNA is released into the solution (Col 21, L25-26), indicates that at least some cells in the liquid mixture undergoes lysis as recited in instant claim 9 and DNA (a macromolecule) is released as recited in instant claim 10.
Regarding claim 11, following the discussion of claim 1, Suh et al. also teach precipitation step, which using precipitation buffer (Col 6, L13). After addition of the precipitation buffer, gentle mixing is performed by repeated aspiration and expulsion of the mixture (Col 6, L56-58).
Regarding claims 12 and 15, Suh et al. teach a method of breaking open cells in a liquid culture and capturing plasmid DNA on a pipette tip column (Col 2, L41-43). The method involves the following steps: 1. cell growth; 2. cell lysis; 3. precipitation of cell debris and other components; 4. capture of plasmid DNA on a pipette tip column; 5. elution of the purified plasmid. All the method steps can be performed using automation in a 96-well format or another microplate format ( e.g., 6, 12, 24, 48, 72 or 384 wells). Steps 1 through 3 can be performed using a single plate (Col 2, L48-57). Lysis buffer comprised of sodium hydroxide and SDS (Col 5, L47-50). Lysis buffer comprised of sodium hydroxide and SDS is in deck position 5 on the robotic instrument. A gentle mixing step follows the addition of the lysis buffer (Col 5, L47-50). In Example 2, the detailed step about the mixing is described: mix using gentle pipette mixing with wide bore 1000 μL pipette tips for 30 back-and-forth cycles of 1 mL/min (Col 16, L16-18). Suh et al. also teach using precipitation buffer (Col 6, L13). After addition of the precipitation buffer, gentle mixing is performed by repeated aspiration and expulsion of the mixture (Col 6, L56-58). After precipitation, Suh et al. teach the step of capture. For the capture step, it is preferred to operate the columns by aspirating and expelling through the open lower end of the column. During the aspiration step, it is desirable to aspirate only the liquid containing the plasmid and to minimize aspiration of cell debris or precipitants as those may clog the column (Col 9, L56-61). Herein the liquid containing the plasmid is the non-precipitated liquid mixture.
Sue et al. do not teach the step of providing a filtrate by passing at least a portion of the non-precipitated liquid mixture through at least one filter, and the filter is a gravity filter. However, such was disclosed by Chen at the time of instant invention.
Chen teaches methods to purify plasmid DNA from host cells (Abstract).
Regarding claim 12, Chen teaches a method of purifying plasmid DNA, comprising a step of a) lysing host cells containing plasmid DNA to obtain a lysate; b) precipitating host cell impurities from the lysate of step a) by adding a first solution comprising at least one monovalent cation and at least one divalent cation; c) centrifuging or filtrating the lysate from step b) to remove the precipitation of the
host cell impurities forming a clarified lysate; d) precipitating plasmid DNA from the clarified lysate of step c) by adding a second solution comprising a first plasmid DNA precipitating agent; and e) collecting the plasmid DNA precipitation by a separation step (parag 0013). Herein the step c) reads on providing a filtrate by passing at least a portion of the non-precipitated liquid mixture through at least one filter, as recited in instant claim.
Regarding claim 15, following the discussion above, Chen teaches the mechanisms of transfer can vary and include any known filtering technique. For example, the liquid can flow down by gravity (parag 0065).
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 Sue et al.’s method of isolating plasmids, and add an extra step of filtration using a gravity filter after precipitation. The only difference between instant claim and Sue et al.’s method of isolating plasmids is instant claim uses an extra step of filtration (i.e., using gravity filter) after precipitation. Given that Chen teaches filtrating the lysate (after precipitation) removes the precipitation of the host cell impurities forming a clarified lysate (parag 0013), one of ordinary skill in the art would have substituted Sue et al.’s method of isolating plasmids without a step of filtration, and use this step of filtration after precipitation depends on the research preference or the purpose to obtain a clarified lysate. This simple substitution of one known element (the method of isolating plasmids having a step of filtration after precipitation) for another known element (the method of isolating plasmids having a step of filtration after precipitation) 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 13, Suh et al. teach using pipette tip column (see Col r, L21, as well asl figure 2). The pipette tip column is made of silica resin, which is evidenced by Takara Bio USA, Inc that Silica Resin column is used to as chromatography column (see p7, parag 4). Suh et al. teach plasmid (DNA) capture using the column (Col 9-10), and one-directional flow through the column can be used for the capture mode provided the flow rate is slow enough to allow the plasmid to be captured by the column
Media (Col 9, L29-32). This teaching reads on “capturing macromolecules by passing at least a portion of the filtrate through a chromatography column” as recited in instant claim. Furthermore, Suh et al. teach the elution of plasmid from the column can be accomplished with back-and-forth flow or one direction flow (Col 11, L22-23)., reads on eluting at least a portion of the macromolecules from the chromatography column as recited in instant claim.
Regarding claim 16, following the discussion above, Suh et al. teach to capture genomic DNA, the pipette tip columns can be unloaded into a vacuum manifold on the MEA instrument. The MEA can then use pipette tips to add the sample to the top of the resin bed and passage of the sample through the pipette tip column can be achieved by gravity or by applying a vacuum. In alternative embodiments, the capture step can be performed with back-and-forth flow (Col 14, L37-43).
Claims 1 and 3-16 are rejected under 35 U.S.C. 103 as being unpatentable over Suh et al. (US 9,328,342 B2, patented in 2016, as cited in IDS) in view of Chen (WO 2009/111336 A2), evidenced by Takara Bio USA, Inc (User manual, 2019), further in view of Lander et al. (US 2002/0151048 A1).
The teaching of Suh et al. and Chen is set forth above.
Regarding claim 14, Suh et al. and Chen do not teach the step of concentrating the plasmid eluted from the chromatography column. However, this was disclosed by Lander et al..
Lander et al. teach methods of isolating clinical-grade plasmid DNA from microbial cells (parag 0012).
Regarding claim 14, Lander et al. teach concentration of the purified plasmid DNA by alcoholic precipitation (including but not limited to ethanol, methanol and isopropanol), or another concentrating method (parag 0012).
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 Sue et al.’s method of isolating plasmids, and concentrates of the purified plasmid DNA by alcoholic precipitation (parag 012). The skilled artisan would have been motivated to using alcoholic precipitation to further concentrate the purified plasmid DNA since Lander et al. teach that alcohol (Such as ethanolic) precipitation is an ideal way to gain a stable bulk product which can be resuspended at high concentrations without the anticipated shear damage which occurs during membrane based concentration (parag 0019). There would be a reasonable expectation of success of concentrating of the purified plasmid DNA by alcoholic precipitation since Lander et al. teach the method of Ethanol precipitation (i.e., parag 0095).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QINHUA GU whose telephone number is (703)756-1176. The examiner can normally be reached M-F: 9:00 - 5:00.
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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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