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 .
Response to Amendment
This office action is responsive to the amendment filed on May 22, 2026. As directed by the amendment: claims 1, 8, 9, 11, 12, 15, and 22 have been amended, no claims have been canceled, and new claims 23-24 have been added. Thus, claims 1-24 are presently pending in the application.
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 1-24 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.
As to claim 1, line 10 recites “…albuterol, which may be in the form of albuterol, one or more pharmaceutically acceptable salts thereof, and/or one or more pharmaceutically acceptable hydrates of any of the foregoing”. Use of the term “may be” renders the claim indefinite as it is not clear if the limitation is required or optional. Examiner suggests amending the language to read --“…albuterol, which is and/or one or more pharmaceutically acceptable hydrates of any of the foregoing”--- to overcome the rejection.
Claims 2-24 are rejected based solely on their dependency to rejected claim 1.
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 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 1-24 are rejected under 35 U.S.C. 103 as being unpatentable over Ashurst et al. (US 6,131,566), in view of Zhu et al. (US 2018/0071231).
As to claim 1, Ashurst discloses an inhaler (metered dose inhaler, col. 5, ln. 40-47) comprising:
a valve 3 (Fig. 1, col. 2, ln. 15-19);
a coating 14 (Fig. 1, col. 2, ln. 9-11);
a pressurized canister 10 (Fig. 1) in fluid communication with the valve 3, the pressurized canister 10 containing a pharmaceutically acceptable inhalable composition that comprises a propellant (col. 1, ln. 66 – col 2, ln. 6); and
a single active agent consisting of albuterol, which may be in the form of albuterol, one or more pharmaceutically acceptable salts thereof, and/or one or more pharmaceutically acceptable hydrates of any of the foregoing (see col. 1, ln. 66 – col. 2, ln. 6: the other active agents are optional and col. 9, ln. 49-51: the formulation consists of albuterol or a physiologically acceptable salt thereof and a fluorocarbon propellant), free albuterol being present in a concentration of 2 milligrams/milliliter (mg/mL) or greater (col. 5, ln. 36-40 discloses “The final aerosol formulation desirably contains 0.005-10% weight to weight ratio, in particular 0.005-5% weight to weight ratio, especially 0.01-1.0% weight to weight ratio, of drug relative to the total weight of the formulation”, which overlaps the claimed range since 0.01-1% w/w of albuterol sulfate would convert to about 0.083-8.3 mg/mL of free base albuterol in an aqueous solution considering the molecular weights of albuterol (239.3) and albuterol sulfate (576.7); see also Ashurst’s claims 37 and 39 at col. 10, ln. 54-67, wherein the drug consists of albuterol sulfate and a propellant and has a w/w% of 0.005 to 10%; since the concentrations overlap the claimed range, a prima facie case of obviousness exists. See MPEP 2144.05 I).
Ashurst does not expressly disclose that the valve has a valve volume of no more than 40 microliters (µL), with the coating being on at least a portion of the valve and comprising the condensation product of a first layer on the valve and a second layer on the first layer; the first layer comprising a silane having one or more reactive silane groups, and the second layer comprising polyfluoropolyether silane.
However, Zhu teaches an inhaler for a drug formulation comprising albuterol, the inhaler including a valve having a valve volume of no more than 40 microliters (µL) (paragraph [0033], last four lines – typical valve sizes range from 20µL to 35 µL); a valve coating on at least a portion of the valve (paragraph [0049]), the coating comprising the condensation product of a first layer on the valve (primer) and a second layer (coating) on the first layer (paragraph [0051]-[0057]);
the first layer comprising a silane having one or more reactive silane groups (paragraph [0053]), and
the second layer comprising a polyfluoropolyether silane (paragraph [0054],[0063]).
Therefore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to modify the inhaler of Ashurst so that the valve has a volume of no more than 40µL, as taught by Zhu, in order to provide a typical valve size for a metered dose inhaler delivering albuterol, since it appears the inhaler of Ashurst would perform equally well with a valve volume of typical size (20µL to 35 µL).
Furthermore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to modify the inhaler of Ashurst so that coating is of the claimed formulation, as taught by Zhu, in order to provide a suitable known alternative coating since it appears the inhaler of Ashurst would perform equally well with the coating formulation in preventing adhesion of drug particles to the inhaler.
Finally, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to modify the inhaler of Alshurst so that the modified coating is applied to the valve of the inhaler in addition to the walls of the canister, as taught by Zhu, in order to insure every surface in contact with the drug is coated and prevented from the particles adhering to its surface during delivery.
As to claim 2, modified Ashurst discloses the inhaler of claim 1, wherein the silane having one or more reactive silane groups comprises a compound of Formula (I)
X3-m (R1)mSi - Q - Si(R2)k X3-k (I)
wherein Ri and R2 are independently selected from C1-C4 alkyl, X is a hydrolysable group or a hydroxy group, m and k are independently 0, 1, or 2 and Q is a divalent organic linking group (see paragraph [0058] of Zhu).
As to claim 3, modified Ashurst discloses the inhaler of claim 2, wherein Q comprises a substituted or unsubstituted C2 to C12 hydrocarbyl chain (see paragraph [0059] of Zhu).
As to claim 4, modified Ashurst discloses the inhaler of claim 1, wherein the silane having one or more reactive silane groups comprises a mixture of two or more of 1,2- bis(trialkoxysilyl) ethane, 1,6- bis(trialkoxysilyl) hexane, 1,8- bis(trialkoxysilyl) octane, 1,4- bis(trialkoxysilylethyl)benzene, bis(trialkoxysilyl)itaconate, and 4,4'-bis(trialkoxysilyl)- 1,1'-diphenyl (paragraph [0059] of Zhu).
As to claim 5, modified Ashurst discloses the inhaler of claim 1, wherein the perfluoropolyether silane is a compound of Formula (Ia)
Rf[Q1-[C(R)2-Si(Y)3-x(R1a)x]y]z (Ia)
wherein:
Rf is a monovalent or multivalent polyfluoropolyether moiety;
Q1 is an organic divalent or trivalent linking group;
each R is independently hydrogen or a C1-4 alkyl group;
each Y is independently a hydrolysable group;
each Ria is independently a C1-8 alkyl or phenyl group;
xis0 or 1 or 2;
y is 1 or 2; and
z is 1, 2, 3, or 4 (see paragraphs [0063]-[0070], [0092]-[0101] of Zhu).
As to claim 6, modified Ashurst discloses the inhaler of claim 5, wherein the compound of Formula (Ia) is a compound of Formula (Ib)
Rf[Q1-[C(R)2-Si(O-)3-x(R1a)x]y]z (Ib)
wherein:
Rf is a monovalent or multivalent polyfluoropolyether segment;
Q1 is an organic divalent or trivalent linking group;
each R is independently hydrogen or a C1-4 alkyl group; and
each R1a is independently a C1-8 alkyl or phenyl group (paragraphs [0063]-[0070],[0092]-[0101] of Zhu).
As to claim 7, modified Ashurst discloses the inhaler of claim 5, wherein the compound of Formula (Ia) is a compound of Formula (Ic)
RfQ1v[Q2w-[C(R4)2-Si(X)3-x(R5)x]y]z (Ic)
wherein:
Rf is a polyfluoropolyether moiety;
Q1 is a trivalent linking group;
each Q2 is an independently selected organic divalent or trivalent linking group;
each R4 is independently hydrogen or a C1-4 alkyl group;
each X is independently a hydrolysable or hydroxyl group;
R is a C1-8 alkyl or phenyl group;
v and w are independently 0 or 1, x is 0 or 1 or 2; y is 1 or 2; and z is 2, 3, or 4 (paragraph [0063]-[0070] of Zhu).
As to claim 8, modified Ashurst discloses the inhaler of claim 5, wherein each of x, y, and z of Formula (Ia) are 1 (paragraph [0099]-[0101] of Zhu).
As to claim 9, modified Ashurst discloses the inhaler of claim 5, wherein y of Formula (Ia) is 0 (paragraph [0100] of Zhu).
As to claim 10, modified Ashurst discloses the inhaler of claim 5, wherein Rf comprises perfluorinated repeating units selected from the group consisting of -(CnF2n)-,-(CF(Z)O)-, -(CF(Z)CnF2n0)-, -(CnF2nCF(Z)O)-, -(CF2CF(Z)O)-, and combinations thereof,
wherein n is an integer from 1 to 6, and
Z is a perfluoroalkyl group, an oxygen-containing perfluoroalkyl group, a perfluoroalkoxy group, or an oxygen-substituted perfluoroalkoxy group, each of which can be linear, branched, or cyclic, and have 1 to 5 carbon atoms and up to 4 oxygen atoms when oxygen-containing or oxygen-substituted and wherein for repeating units including Z the number of carbon atoms in sequence is at most 6 (paragraph [0071] of Zhu).
As to claim 11, modified Ashurst discloses the inhaler of claim 10, wherein n is an integer from 1 to 4, optionally 1 to 3 (paragraph [0071] of Zhu).
As to claim 12, modified Ashurst discloses the inhaler of claim 10, wherein Z is a perfluoroalkyl group, an oxygen- containing perfluoroalkyl group, a perfluoroalkoxy group, or an oxygen-substituted perfluoroalkoxy group (paragraph [0071] of Zhu).
As to claim 13, modified Ashurst discloses the inhaler of claim 5, wherein Rf is selected from the group consisting of -CF2O(CF2O)m(C2F4O)pCF2-, CF(CF3)O(CF(CF3)CF2O)pCF(CF3) , -CF2O(C2F40)pCF2-, -(CF2)3O(C4FSO)p(CF2)3-,-CF(CF3)-(OCF2CF(CF 3))pO-CtF2t-O(CF(CF3)CF2O)pCF(CF3)-, wherein t is 2, 3 or 4, m is 1 to 50, and p is 3 to 40 (paragraph [0071] of Zhu).
As to claim 14, modified Ashurst discloses the inhaler of claim 1, wherein the valve 3 comprises a valve stem (see Ashurst Fig. 1) and the coating is disposed on at least a portion of the valve stem (see paragraph [0075] of Zhu).
As to claim 15, modified Ashurst discloses the inhaler of claim 1, wherein the albuterol, one or more pharmaceutically acceptable salts thereof, and/or one or more pharmaceutically acceptable hydrates of any of the foregoing is albuterol sulfate (see Ashurst at col. 2, ln. 52-54).
As to claim 16, modified Ashurst discloses the inhaler of claim 1, wherein the free albuterol is present in a concentration of 2.5 mg/mL or greater (see Ashurst at col. 5, ln. 36-40 discloses “The final aerosol formulation desirably contains 0.005-10% weight to weight ratio, in particular 0.005-5% weight to weight ratio, especially 0.01-1.0% weight to weight ratio, of drug relative to the total weight of the formulation”, which overlaps the claimed range since 0.01-1% w/w of albuterol sulfate would convert to about 0.083-8.3 mg/mL of free base albuterol in an aqueous solution considering the molecular weights of albuterol (239.3) and albuterol sulfate (576.7); see also Ashurst’s claims 37 and 39 at col. 10, ln. 54-67, wherein the drug consists of albuterol sulfate (and a propellant) and has a w/w% of 0.005 to 10%; since the concentrations overlap the claimed range, a prima facie case of obviousness exists. See MPEP 2144.05 I).
As to claim 17, modified Ashurst discloses the inhaler of claim 1, wherein the valve volume is no more than 35 µL, (paragraph [0033] of Zhu, last four lines – 20-35 µL).
As to claim 18, modified Ashurst discloses the inhaler of claim 1, further comprising an actuator (col. 2, ln. 23-28), but lacks detailed description as to the limitation that, when actuated, the actuator releases about 70 micrograms (µg) to about 140 µg. However, Zhu teaches an actuator for a metered dose inhaler that releases 16 mcg to 116 mcg, or in particular 55-75 µg, of albuterol sulfate per actuation (paragraph [0039]), which overlaps the claimed range. Therefore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to modify the inhaler of Ashurst so that the amount of formulation released is within the claimed range, as taught by Zhu, in order to provide a suitable effective dose size to treat a particular patient.
As to claim 19, modified Ashurst discloses the inhaler of claim 1, wherein the valve 3 is a metered valve (see Ashurst, Fig. 1, col. 2, ln. 20-23).
As to claim 20, modified Ashurst discloses the inhaler of claim 1, but lacks detailed description as to the inhaler further comprising a dose counter. However, Zhu teaches a metered dose inhaler having a dose counter (paragraph [0042] of Zhu). Therefore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to modify the inhaler of Ashurst so that it further comprises a dose counter, as taught by Zhu, so that he patient can keep track of how many doses the have taken or how many the have left before needing a refill.
As to claim 21, modified Ashurst discloses the inhaler of claim 1, wherein the propellant is HFC-134a (see Ashurst at col. 4, ln. 1-6: in particular, 1,1,1,2-tetrafluoroethane also known as "propellant 134a" or "P 134a).
As to claim 22, modified Ashurst discloses a method of activating the inhaler of claim 1, the method comprising actuating the inhaler of clam 1 to release the albuterol, one or more pharmaceutically acceptable salts thereof, and/or one or more pharmaceutically acceptable hydrates from the inhaler (see Ashurst, col. 3, ln. 63-66).
As to claim 23, modified Ashurst discloses the inhaler of claim 1, wherein the free albuterol is present in a concentration of 4 mg/mL or greater (see Ashurst at col. 5, ln. 36-40 which discloses “The final aerosol formulation desirably contains 0.005-10% weight to weight ratio, in particular 0.005-5% weight to weight ratio, especially 0.01-1.0% weight to weight ratio, of drug relative to the total weight of the formulation”, which overlaps the claimed range since 0.01-1% w/w of albuterol sulfate would convert to about 0.083-8.3 mg/mL of free base albuterol in an aqueous solution considering the molecular weights of albuterol (239.3) and albuterol sulfate (576.7); see also Ashurst’s claims 37 and 39 at col. 10, ln. 54-67, wherein the drug consists of albuterol sulfate (and a propellant) and has a w/w% of 0.005 to 10%; since the concentrations overlap the claimed range, a prima facie case of obviousness exists. See MPEP 2144.05 I).
As to claim 24, modified Ashurst discloses the inhaler of claim 1, wherein the free albuterol is present in a concentration of 4.5 mg/mL or greater (see Ashurst at col. 5, ln. 36-40 which discloses “The final aerosol formulation desirably contains 0.005-10% weight to weight ratio, in particular 0.005-5% weight to weight ratio, especially 0.01-1.0% weight to weight ratio, of drug relative to the total weight of the formulation”, which overlaps the claimed range since 0.01-1% w/w of albuterol sulfate would convert to about 0.083-8.3 mg/mL of free base albuterol in an aqueous solution considering the molecular weights of albuterol (239.3) and albuterol sulfate (576.7); see also Ashurst’s claims 37 and 39 at col. 10, ln. 54-67, wherein the drug consists of albuterol sulfate (and a propellant) and has a w/w% of 0.005 to 10%; since the concentrations overlap the claimed range, a prima facie case of obviousness exists. See MPEP 2144.05 I).
Response to Arguments
Applicant's arguments filed May 22, 2026 have been fully considered but are moot because the arguments do not apply to any of the references being used in the current rejection.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALERIE L WOODWARD whose telephone number is (571)270-1479. The examiner can normally be reached on Monday - Friday 8:30 am - 4:30 pm.
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/VALERIE L WOODWARD/Primary Examiner, Art Unit 3785
