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
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(a-d) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. NL2027229, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The foreign application fails to disclose features such as the moderate operating pressure is held below 10 MPa and said velocity less than 100 m/s.
As such, the instant application has been awarded an effective filing date of 12/24/2021.
Information Disclosure Statement
The Information Disclosure Statement(s) have been reviewed by the examiner and are found to comply with the provisions of 37 CFR 1.97, 1.98, and MPEP § 609.
Drawings
The drawing(s) have been reviewed by the examiner and are found to comply with the provisions of 37 CFR 1.81 to 1.85.
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 2, 4, 6, 10, 14, 15, 17, and dependents therein 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.
Regarding claims 4, 6, 14, 15, and 17, the phrases "like DNA or RNA", “in particular”, and “preferably” render 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).
Regarding claim 2, the metes and bounds of phrases like “complex proteins”, “large biological molecules”, and “large vesicles” are unclear, since one of ordinary skill in the art would not understand when a protein becomes “complex”, or a vesical becomes “large”, for example.
Regarding claim 10, the limitation “narrowing from said inlet entrance to said outlet at substantially a tapering between 5 and 45 degrees” is unclear, since the word “substantially” may modify the term “tapering”, rather than the claimed range. Examiner recommends instead reciting “a tapering between substantially 5 and 45 degrees”.
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 – 11, 15 – 17, and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nijdam (US 20180353977) in view of Patel (US 20020088781) in view of Eason (US 20040159321).
1. Nijdam discloses a method for delivering aerosol spray in an atmosphere (see [0001, 0003], Fig. 1) comprising: providing a pharmaceutical liquid ([0019], [0025]); pressurizing said liquid to a moderate operating pressure (p) to provide a pressurized liquid ([0014]; fluid may pass through the sprayer only when its supply pressure has reached the threshold value, see [0063]); and feeding said pressurized liquid through a spray nozzle orifice (see Fig. 1, 7), having a channel length (L) between an inlet and an outlet of said orifice and an average channel diameter (H) between said inlet and said outlet (see Figs. 5 and 6, where channel length is the membrane 6 thickness and channel diameter is the orifice 7 diameter), to create a liquid stream of said liquid formulation with a velocity (see Fig. 1, [0001]); wherein said moderate operating pressure is held below 10 MPa (0.2 to 1 MPa, see [0014, 0065]); wherein said orifice has a channel length (L) that is shorter than said average channel diameter (H) (see illustration in Figs. 5 and 6, and note [0082, 0062], where the lower end range of 0.1 micron length is shorter than the lower end range 0.5 micron diameter, and upper end range of 2 micron length is shorter than 10 microns diameter); and wherein said liquid stream is collected at said outlet as a jet of consecutive liquid droplets (see [0001-0002], Fig. 1).
However, Nijdam does not disclose a method for delivering nanoparticles in an atmosphere, comprising: providing nano-particles having a particle length (λ) in a liquid to form a liquid formulation; and wherein each of the droplets contain at least one nanoparticle of said nanoparticles. Nonetheless, Patel discloses a method for delivering nanoparticles in an atmosphere (drugs may include peptides and hormones such as insulin and EPO, with known diameters in the nanometer length, see [0055], conclusion below; note also claim 3, protein, antibody, or nucleotide with molecular weight greater than 100 g/mol are considered nanoparticles; see Fig. 9 for delivery to atmosphere), comprising: providing nano-particles having a particle length (λ) in a liquid to form a liquid formulation (see [0056], “preferred formulation consist essentially of pharmaceutically active drug and a pharmaceutically acceptable carrier (e.g. water…)”); and wherein each of the droplets contain at least one nanoparticle of said nanoparticles (see [0059] – [0061], the aerosol particles are all formed by the formulation comprising the drug such as nanoparticle). The liquid is pressurized below 10 MPa, and provided to a membrane comprising the nozzle, see [0081]. Therefore, according to the teachings of Patel, it would have been obvious to a person having ordinary skill in the art at the time the invention was filed to modify the method of Nijdam to deliver nanomolecular drugs such as peptides, hormones, and encoding polynucleotides for the benefit of biologically active targeted therapeutics such as insulin or EPO.
While the modified Nijdam discloses that the velocity of the aerosolized formulation moving out of the porous membrane can have a relative velocity that is substantially zero with reference to patient inhalation flow (see Patel, [0063]), the modified Nijdam does not disclose wherein said velocity is less than 100 m/s. Nonetheless, Eason discloses that the typical inhalation velocity is 2 m/s. It is additionally noted that, using the operating pressure and areas disclosed within the device of Nijdam (sharing same inventor and likely device, undisclosed and unillustrated in the instant application), to deliver water-based drugs as discussed in Patel, a stream velocity well within 100 m/s would be expected (assuming an input pressure of 3 bar and output pressure of 1 bar or atmosphere as discussed in Nijdam [0014], with an input diameter 100 and nozzle diameter 10 as discussed in Nijdam, [0061 – 0062], using the density of water at 1,000 kg/m^3, calculates an output velocity of approximately 20 m/s; calculated according to Bernoulli’s equation and the continuity equation, see conclusion below for formulas). Therefore, it would have been obvious to a person having ordinary skill in the art at the time the invention was filed to modify the stream velocity of Nijdam within applicant’s claimed range to thereby approach the typical inhalation velocity as taught in Eason, for the benefit of suitably entraining the medicament in the user flow stream in a comfortable manner that cannot jet, pierce, or hurt the user. Examiner additionally notes that one of ordinary skill in the art would expect a stream velocity well within 100 m/s to be the predictable result of operating the sprayer under typical conditions per the discussion above.
2. Nijdam as modified discloses the method according to claim 1, wherein said liquid formulation comprises shear stress-sensitive nanoparticles taken from a group, containing complex proteins, large biological molecules, long chain DNA & RNA, viruses, large vesicles, liposomes, bacteriophages, and antibodies (see Patel, [0055], EPO is a complex protein modified with carbohydrates); and wherein said orifice has a channel length (L) that is shorter than half said average channel diameter (H) (see Nijdam, lower and upper values are both 1/5 shorter channel length per [0082, 0062], where the lower end range of 0.1 micron length is 1/5 shorter than the lower end range 0.5 micron diameter, and upper range of 2 micron length is 1/5 shorter than 10 microns diameter; see also Figs. 5 – 6; given the relationship between lower and upper end values, examiner considers Nidjam’s disclosure sufficiently specific to the claimed range).
3. Nijdam as modified discloses the method according to claim 2, wherein said orifice has a channel length (L) that is at most a quarter of said average channel diameter (H) (see Nijdam, lower and upper values are both 1/5 shorter channel length per [0082, 0062], where the lower end range of 0.1 micron length is 1/5 shorter than the lower end range 0.5 micron diameter, and upper range of 2 micron length is 1/5 shorter than 10 microns diameter; see also Figs. 5 – 6; given the relationship between lower and upper end values, examiner considers Nidjam’s disclosure sufficiently specific to the claimed range).
4. Nidjam as modified discloses the method according to claim 2, wherein said liquid formulation comprises protein and/or antibody molecules, and/or nucleotide compounds like DNA or RNA molecules, with a molecular weight that is larger than 100.000 g/mol (see Patel, [0055], EPO has molecular weight of 30,000 g/mol, see conclusion below).
8. Nidjam discloses the method according to claim 2, wherein said nozzle orifice has a substantially constant diameter (H) that is between 1 micron and 10 micron (see [0062] and Figs. 5 - 6).
9. Nidjam discloses the method according to claim 2, wherein said nozzle orifice has an average diameter (H) between 1 micron and 10 micron (see [0062]). Nidjam does not disclose wherein said orifice tapers over at least part of said length from said inlet to said outlet. Patel discloses wherein said orifice tapers over at least part of said length from said inlet to said outlet (see claim 1, Fig. 1). Therefore, it would have been obvious to a person having ordinary skill in the art at the time the invention was filed to modify the nozzle orifice of Nidjam according to the taper of Patel for the benefit of reducing applied pressure, see [0009].
10. Nidjam as modified discloses the method according claim 9, wherein said nozzle orifice is provided with a positive taper, narrowing from said inlet entrance to said outlet at substantially a tapering between 5° and 45° (see Figs. 1 – 5, of Patel, wherein the provided dimensions in the figures calculate to a taper within the claimed range).
11. Nidjam discloses the method according to claim 1, wherein an inner wall of said nozzle orifice is provided with a hydrophobic slip flow enabling coating ([0034]).
15. Nidjam as modified discloses the method according to claim 1, wherein said nano-particles comprises macromolecules with a molecular weight that is larger than 100.000 g/mol (see Patel, [0055], EPO has molecular weight of 30,000 g/mol); and wherein said macromolecules have a ratio λ.sub.max/λ of at least 2, and preferably a ratio λ.sub.max/λ of at least 4 (proteins have range of λ.sub.max/λ of at least 2 per applicant’s specification, p. 4, 4 – 9).
16. Nidjam discloses the method according to claim 1, wherein said nozzle orifice is part of a collection of substantially identical nozzle orifices (see Fig. 7, multiple nozzles 7) that extend through a common membrane layer (23) that is supported by a substrate (15), wherein said substrate has at least one cavity extending to said nozzle orifices of said collection of orifices (3), and wherein said liquid formulation is delivered at said operating pressure jointly to said cavities to supply said nozzle orifices of said collection of orifices ([0080]).
17. Nidjam as modified discloses the method according to claim 3, wherein said liquid formulation comprises protein and/or antibody molecules, and/or nucleotide compounds like DNA or RNA molecules, with a molecular weight that is larger than 100.000 g/mol (see Patel, [0055], EPO has molecular weight of 30,000 g/mol).
20. Nidjam discloses the method according to claim 3, wherein said nozzle orifice has a substantially constant diameter (H) that is between 1 micron and 10 micron (see [0062] and Figs. 5 - 6).
Claim(s) 6, 7, and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nijdam (US 20180353977) in view of Patel (US 20020088781) in view of Eason (US 20040159321) in view of Dunne (US 20210228822).
6. Nijdam discloses the Method according to claim 2, but does not disclose wherein said liquid formulation comprises lipid nanoparticles or liposomes, in particular lung surfactants, of which said length λ is larger than 20 nanometre. Nonetheless, Dunne discloses a pressurized spray device for jet delivery via nozzle orifice, see Figs. 1 and 3, wherein said liquid formulation comprises lipid nanoparticles or liposomes ([0043 – 0044]), of which said length λ is larger than 20 nanometre (see general teaching of nanoparticle length in [0042]). Therefore, it would have been obvious to a person having ordinary skill in the art at the time the invention was filed to modify the method of Nijdam according to the lipid nanoparticles of Dunne for the benefit of additional pathways in therapeutics such as encapsulation of proteins, macromolecules, and localized drug uptake, see [0044].
7. The modified Nidjam discloses the method according to claim 6, wherein said liquid formulation comprises vesicles that have a content comprising nanoparticles taken from a group, containing proteins, biological molecules, DNA, RNA, vaccines, viruses, bacteriophages and antibodies (see [0044] in Dunne, the lipid nanoparticle encompasses the macromolecular protein) with a molecular weight above 100.000 Da (see Nidjam, [0055], EPO has a molecular weight of 30,000 Da).
19. The modified Nidjam discloses the method according to claim 3 wherein said liquid formulation comprises lipid nanoparticles or liposomes, in particular lung surfactants, of which said length 2 is larger than 20 nanometre (see Dunne per claim 6 above).
Claim(s) 5 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nijdam (US 20180353977) in view of Patel (US 20020088781) in view of Eason (US 20040159321) in view of Chang (“Phage Therapy for Respiratory Infections”), as evidenced by ViralZone (“Fiersviridae”).
5. Nijdam discloses the method according to claim 2, but does not disclose wherein said liquid formulation comprises bacteriophages with an average size larger than 20 nanometre. Nonetheless, Chang discloses a method of creating aerosols to produce viable bacteriophage at 1 um diameter for inhalator treatment, see p. 5, para. 3. The most shear resistant bacteriophage Leviviridae (Fiersviridae) has an average size larger than 20 nanometers, as evidenced by ViralZone. Therefore, it would have been obvious to a person having ordinary skill in the art at the time the invention was filed to modify the method of Nijdam to include the bacteriophage of Chang for the benefit of producing an aerosol used in inhalatory treatments such as for bacterial respiratory infections, see abstract.
18. Nijdam as modified discloses the method according to claim 3, wherein said liquid formulation comprises bacteriophages with an average size larger than 20 nanometre (see Change as per claim 5 above).
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nijdam (US 20180353977) in view of Patel (US 20020088781) in view of Eason (US 20040159321) in view of Bell (US 10980954), as evidenced by Wikipedia (https://en.wikipedia.org/wiki/Reynolds_number).
12. Nijdam discloses the method according to claim 1, but does not disclose wherein a product of a mass density (ρ) of said fluid, a fluid velocity (V) inside said orifice and said nozzle diameter (H) divided by a viscosity (η) of said fluid, expressed as ρ.Math.V.Math.H/η, is maintained below 2.500. Nonetheless, Bell discloses that lower Reynold’s number below 2,000 is more efficient and reduces turbulence (c. 4: 48-59). As evidenced by Wikipedia, the Reynold’s number is a product of a mass density (ρ) of said fluid, a fluid velocity (V) inside said orifice and said nozzle diameter (H) divided by a viscosity (η) of said fluid, expressed as ρ.Math.V.Math.H/η. Therefore, it would have been obvious to a person having ordinary skill in the art at the time the invention was filed to modify the nozzle of Nijdam according to the Reynold’s number of Bell for the benefit of avoiding turbulent flow, thus increasing efficiency of the nozzle.
Allowable Subject Matter
Claim 13 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Dependent claim 14 would additionally be allowable upon obviating the rejection under 35 USC 112(b).
Claims 13 and 14 in the instant application have not been rejected using prior art because no references, or reasonable combination thereof, could be found which disclose, or suggest, all the features of claims 13 and 14. Nijdam discloses the method of claim 1, but fails to disclose the method as recited, furthermore in combination wherein said nanoparticles have a maximum particle length λ.sub.max before breakage upon elongation; wherein said liquid formulation is subjected to a wall shear rate γ.sub.wall [per second] while passing through said spray nozzle orifice; and wherein said liquid formulation is exposed within said spray nozzle orifice to said wall shear rate during a shear time (t) that is less than λ.sub.max/(λ.Math.γ.sub.wall) seconds. While the prior art discloses methods for calculating elongation strain rate, see the provided NPL dated 06/22/2023 to “Studies on Aerosol Delivery of Plasmid DNA”, p. 943, column 1, as well as calculation of wall strain rate in a similar spray nozzle/dimensions to Dunne, see [0125 – 0127], the references fail to disclose all the features of claim 13.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Targeted Delivery of Erythropoietin Hybridized with Magnetic Nanocarriers for the Treatment of Central Nervous System Injury: A Literature Review – listing the size of EPO on p. 9292, para. 1.
Https://pubchem.ncbi.nlm.nih.gov/compound/Epoetin-Alfa - listing the molecular weight of EPO.
Google snapshot, see provided NPL for Bernoulli’s equation and Continuity Equation
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRADLEY H PHILIPS whose telephone number is (571)270-5180. The examiner can normally be reached 8:00 - 5:00 M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brandy Lee can be reached at (571) 270-7410. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRADLEY H PHILIPS/Primary Examiner, Art Unit 3799
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