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 .
Claim Objections
Claims 1 and 4 are objected to because of the following informalities: “the second streams” should read “the second stream”. Appropriate correction is required.
Claim 12 is objected to because of the following informalities: “optionally at a concentration in the range of 0.1 mol% to 2 mol% cholesterol” should read “optionally at a concentration in the range of 0.1 mol% to 2 mol%, cholesterol”. 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 1-4, 8-9, 12, 15, 19-20, 22-25, 27-28, 30-31, and 34-35 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 "the flow rate ratio" in line 10 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 1, the claim recites “a reaction chamber” in line 8 of the claim. It’s not clear if it’s referring to “a reaction chamber” recited in line 6 of the claim.
Claims 2-4, 8-9, 12, 15, 19-20, 22-25, 27-28, 30-31 and 34-35 are rejected for depending from claim 1.
Claim 3 recites the limitation "the total flow rate" in line 1 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim 4 recites the limitation "the total flow rate" in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 12, the claim is rejected from claim 11, which is cancelled. It’s not clear if it’s intended to depend from claim 1.
Regarding claim 12, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The term “small molecules” in claim 15 is a relative term which renders the claim indefinite. The term “small” is not defined by the claim, 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. The molecule size of the active pharmaceutical ingredient in the claim has been rendered indefinite by the use of the term "small".
Claim 19 recites the limitation "the average particle size" in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim 22 recites the limitation "the pressure" in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 22 and 34 recite the broad recitation 0.1 to 120 bar, and the claim also recites 1 to 40 bar which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 23 recites the limitation "the distance" in line 12 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim 23 recites the limitation "the diameter" in line 13 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claims 24-25, 27-28, 30-31, 34-35 are rejected for depending from claim 23.
Claim 24 recites the limitation "the centre" in line 5-6 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 25, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 28 recites the limitation "the diameter of the upstream portion" in line 7 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim 28 recites the limitation "the diameter of the downstream portion" in line 8 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 28, the claim recites the limitation “the nozzle”. It’s not clear if it’s referring to “the nozzle of the first or second fluid inlet” recited in claim 27.
Claim 31 recites the limitation "the second orifice diameter" in line 3 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim 35 recites the limitation "the orifice of the second nozzle" in line 3 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim 35 recites the limitation "the orifice of the first nozzle" in line 3 of the claim. There is insufficient antecedent basis for this limitation in the claim.
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.
Claim(s) 1-4, 8-9, 19-20, 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over MacSweeney et al. (2020/0060321).
Regarding claims 1-2, MacSweeney et al. discloses a method for producing a dispersion of nanoparticles comprising at least one amphiphilic lipid, wherein the method comprising the steps of:
Providing a first stream comprising an organic solvent and the amphiphilic lipid;
Providing a second stream comprising an aqueous solvent;
Pumping the first stream under a raised pressure through a first nozzle and pumping the second streams under a raised pressure through a second nozzle into a reaction chamber; wherein the first nozzle is located at an angle within the range of 90 to 180 degrees from the second nozzle;
Colliding the first stream and the second streams frontally in a reaction chamber (see abstract, para 31-46, claim 10).
MacSweeney et al. does not teach the angle of about 180 degrees and wherein the flow rate ration between the first stream and the second stream is in a range from 1:1.5 to 1:4.5. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the flow rate ratio between the first stream and the second stream since MacSweeney et al. teaches that solvent and nonsolvent flow rates are result effective variables that affect the particle size (see para 31-32, 34, 45-46). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the angle of the nozzles relative to each other depending on the number of nozzles used.
Regarding claim 3, MacSweeney et al. discloses wherein the total flow rate is more than 0.2 mil/min (see para 46 and claim 12). MacSweeney et al. does not teach wherein the total flow rate is in the range of from 1 ml/min to 1,000 ml/min, or form 5 ml/min to 800 ml/min. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the total flow rate since MacSweeney et al. teaches that the solvent and nonsolvent flow rates are result effective variables that affect the particle size (see para 31-32, 34, 45-46).
Regarding claim 4, MacSweeney et al. discloses wherein the total flow rate is more than 0.2 mil/min (see para 46 and claim 12). MacSweeney et al. does not teach wherein the total flow rate is in the range of from 100 ml/min to 500 ml/min and wherein the flow rate ratio between the first stream and the second stream is in a range from 1:1.2 to 1:2.5, or in a range from 1:2 to 1:4. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the total flow rate and the flow rate ration between the first stream and the second stream since MacSweeney et al. teaches that the solvent and nonsolvent flow rates are result effective variables that affect the particle size (see para 31-32, 34, 45-46).
Regarding claim 8, MacSweeney et al. discloses wherein the nanoparticles are liposomes formed by mixing Omega fatty acids with phospholipids (para 21-29).
Regarding claim 9, MacSweeney et al. discloses wherein the amphiphilic lipid is fatty acids (abstract).
Regarding claim 19, MacSweeney et al. discloses wherein the average particle size of the nanoparticles is from 25-500 nm (para 9, 11, 17, 20, claim 1, 6, 10, 16), which overlaps with the claimed range. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the average particle size since MacSweeney teaches that the particle size can be controlled by the temperature at which the solvent and nonsolvent collide, the flow rates of the solvent and the nonsolvent, and/or the amount of gas in the microreactor (para 32-34, 42-45, 51).
Regarding claim 20, MacSweeney et al. discloses a step of providing a jet impingement reactor that comprises the reaction chamber, the first nozzle and the second nozzle (para 31-33, 40, claim 10).
Regarding claim 22, MacSweeney et al. discloses wherein the pressure of each stream is independently selected from a value in the range of 0.75-25 bar (para 47, claim 14).
Claim Rejections - 35 USC § 103
Claim(s) 12, 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over MacSweeney et al. as applied to claim 1 above, and further in view of Zhu et al. (2016/0256387).
Regarding claim 12, MacSweeney et al. discloses wherein the first stream comprises a phospholipid (para 21-29), and further optionally, an organic solvent selected from an alcohol such as ethanol, acetone, THF (para 36). MacSweeney et al. does not teach wherein the first stream comprises a PEGylated lipid, optionally at a concentration in the range of 0.1 mol% to 2 mol$ cholesterol, and a cationic lipid. However, Zhu et al. teaches a liposomal pharmaceutical formulation can include a plurality of liposomes. A liposome can include a lipid layer comprising an unsaturated phospholipid, a cholesterol, a cationic lipid and preferably a pegylated phospholipid (see abstract). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify MacSweenety et al. with the teaching of Zhu et al. since Zhu et al. teaches that PEGylated lipids, cholesterol, and cationic lipid are common ingredients in a liposome. Zhu et al. further teaches the lipid layer comprises about 0-20%, preferably 1-10%, (molar) pegylated phospholipid (para 16, 82, claim 5).
Regarding claim 15, MacSweeney et al. as modified teaches wherein the first or the second stream further comprises an active pharmaceutical ingredient (abstract), wherein the active pharmaceutical ingredient is selected from the group of small molecules, peptides, and nucleic acids (para 54-59, 78).
Allowable Subject Matter
Claims 23-25, 27-28, 30-31, 34-35 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: Regarding claim 23, the prior art does not teach the reaction chamber having a substantially spheroidal overall shape, a fluid outlet arranged at a third position, said third position being located on a second central axis of said chamber, the second central axis being perpendicular to the first central axis; wherein the distance between the first nozzle and the second nozzle is the same or smaller than the diameter of the reaction chamber along the first central axis.
Conclusion
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/X.H.L/Examiner, Art Unit 1742 /CHRISTINA A JOHNSON/Supervisory Patent Examiner, Art Unit 1742
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