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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 25th, 2026 has been entered.
Response to Arguments
Applicant's arguments filed on 02/25/2026 have been fully considered.
Applicant's arguments, see Remarks, under “Rejections under 35 U.S.C. § 103”, on page 6, filed on 02/25/2025, have been fully considered but they are not persuasive since, in response to applicant’s argument that the office has not set forth a proper prima facie case obviousness regarding the concentration of chemotherapeutic agent range, as set forth in the MPEP 2144.05; In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness does exist. The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range, therefore the rejection set forth in the previous office actions has set forth a proper prima facie case of obviousness regarding the ranges of the concentration of chemotherapeutic agent.
Applicant’s arguments, see Remarks, under “Rejections under 35 U.S.C. § 103”, on page 6-7, filed on 02/25/2025, regarding the argument that Pirfenidone and pyridine analog compounds are not chemotherapeutic agents because they do not induce cell death or prevent cell growth, with respect to the rejection of claim 1 under 35 U.S.C. 103 rejection, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of an additional disclosure in the previously applied reference, Surber.
Applicant's arguments, see Remarks, under “Rejections under 35 U.S.C. § 103”, on page 7, filed 02/25/2025 have been fully considered but they are not persuasive since in response to applicant’s argument that a person of skill in the art would have understood that inhalation of an aerosolized composition is distinct from bathing tissue directly in a liquid composition, according to Merriam-Webster, the definition of “bathing” is “moisten, wet” and/or “to apply water or a liquid medicament to”, which Surber discloses applying liquid medicament to the lungs through an inhaled dose being administered with a liquid nebulizer, therefore bathing the lung tissue in the liquid formulation.
Applicant’s arguments, see Remarks, under “Rejections under 35 U.S.C. § 103”, on page 7-8, regarding modifying the method of Surber to administer a lower concentration of therapeutic agent to maintain an effective dose delivered to the lung tissue, filed on 02/25/2025, have been considered but are moot because the explanations given above.
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.
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 1, 3, 9 and 30 are rejected under 35 U.S.C. 102(a) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Surber (US Pub No. 20150196543 A1).
Regarding claim 1, Surber discloses a method for treating lung cancer in a subject, comprising: administering a liquid formulation (“aqueous solution” – Para [0005]) comprising a chemotherapeutic agent directly (“pirfenidone or a pyridine” – Para [0005]) to a lung tissue in the subject (“after administration of the inhaled dose, achieves lung deposition…” – Para [0005]), wherein the concentration of a chemotherapeutic agent in the liquid formulation is from about 0.1 mg/ml (100,000 ng/mL) to about 20 mg/mL (20,000,000 ng/mL)(Para [0005]), thus Surber does disclose the concentration of 100,000 ng/mL; and
Wherein the administering comprises locally bathing the lung tissue in the liquid formulation (“each inhaled dose is administered with a liquid nebulizer” – Para [0005]).
In the alternative, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the concentration of the chemotherapeutic agent of Surber to have a concentration in the range between 2,000 ng/mL to about 100,000 ng/mL because the range disclosed by Surber and the claimed range have overlapping endpoints. As set forth in MPEP 2144.05, the optimization of a concentration would have been considered a matter of routine experimentation to discover workable ranges, making it non-inventive. Further, applicant places no criticality on the range claimed, indicating simply that the concentration of a chemotherapeutic agent in the liquid formulation is from “2,000 ng/mL to about 100,000 ng/mL” (Para [0044]).
Regarding claim 3, Surber discloses the method for treating lung cancer set forth above, wherein the concentration of chemotherapeutic agent in the liquid formulation is from about 0.1 mg/ml (100,000 ng/mL) to about 20 mg/mL (20,000,000 ng/mL)(Para [0005]); thus Surber does disclose the concentration of 100,000 ng/mL.
In the alternative, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the concentration of the chemotherapeutic agent of Surber to have a concentration in the range between 25,000 ng/mL to about 100,000 ng/mL because the range disclosed by Surber and the claimed range have overlapping endpoints. As set forth in MPEP 2144.05, the optimization of a concentration would have been considered a matter of routine experimentation to discover workable ranges, making it non-inventive. Further, applicant places no criticality on the range claimed, indicating simply that the concentration of a chemotherapeutic agent in the liquid formulation is from “25,000 ng/mL to about 100,000 ng/mL” (Para [0044]).
Regarding claim 9, Surber discloses the method for treating lung cancer set forth above, wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than 15% of the plasma Cmax for the chemotherapeutic agent from systemic administration (See modified Fig.5 below, Para [0695]). The graph below shows the difference in plasma Cmax between the inhaled chemotherapeutic agent compared to the oral systemic administration of the chemotherapeutic agent, (7.8 x 0.15 = 1.17, 1.17 > 0.4).
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Regarding claim 30, Surber discloses the method for treating lung cancer set forth above, wherein the administering comprises filling all or part of the lung with the liquid formulation (Para [0012]).
Claims 4-8 and 12-20 are rejected under 35 U.S.C. 103 as being unpatentable over Surber in view of Hsia et al. (US Pub No. 20190262376 A1, herein, Hsia).
Regarding claim 4, Surber discloses the method for treating lung cancer set forth above, wherein the concentration of chemotherapeutic agent in the liquid formulation is from about 0.1 mg/ml (100,000 ng/mL) to about 20 mg/mL (20,000,000 ng/mL)(Para [0005]).
However, Surber fails to explicitly disclose a concentration in the range between 30,000 ng/mL to about 50,000 ng/mL.
Hsia teaches that the quantity of therapeutic composition to be administered, according to unit dose, depends on effect desired. Hsia further recognizes that the actual dosage amount of the therapeutic composition administered to a subject is determined by physical and physiological factors, such as body weight, age, health, sex of the subject, previous or concurrent therapeutic interventions, idiopathy of the patient, the route of administration, etc. (Para [0053]). Hsia further teaches that the claimed range is within a range understood to be appropriate for the intended use.
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have optimized the concentration of the chemotherapeutic agent of Surber to have a concentration in the range between 30,000 ng/mL to about 50,000 ng/mL, as suggested by Hsia to give the appropriate dose for the individual subject. Further, applicant places no criticality on the range claimed, indicating simply that the concentration of a chemotherapeutic agent in the liquid formulation is from “30,000 ng/mL to about 50,000 ng/mL” (Para [0044]).
Regarding claim 5, Surber discloses the method for treating lung cancer set forth above, wherein the concentration of chemotherapeutic agent in the liquid formulation is from about 0.1 mg/ml (100,000 ng/mL) to about 20 mg/mL (20,000,000 ng/mL)(Para [0005]).
However, Surber fails to explicitly disclose a concentration in the range between 2,000 ng/mL to about 20,000 ng/mL.
Hsia teaches that the quantity of therapeutic composition to be administered, according to unit dose, depends on effect desired. Hsia further recognizes that the actual dosage amount of the therapeutic composition administered to a subject is determined by physical and physiological factors, such as body weight, age, health, sex of the subject, previous or concurrent therapeutic interventions, idiopathy of the patient, the route of administration, etc. (Para [0053]). Hsia further teaches that the claimed range is within a range understood to be appropriate for the intended use.
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have optimized the concentration of the chemotherapeutic agent of Surber to have a concentration in the range between 2,000 ng/mL to about 20,000 ng/mL, as suggested by Hsia to give the appropriate dose for the individual subject. Further, applicant places no criticality on the range claimed, indicating simply that the concentration of a chemotherapeutic agent in the liquid formulation is from “2,000 ng/mL to about 20,000 ng/mL” (Para [0044]).
Regarding claim 6, Surber discloses the method for treating lung cancer set forth above, wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than about 401 ng/mL (Fig.5).
However, Surber fails to explicitly disclose wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than about 100 ng/mL.
Hsia teaches that the quantity of therapeutic composition to be administered, according to unit dose, depends on effect desired. Hsia further recognizes that the actual dosage amount of the therapeutic composition administered to a subject is determined by physical and physiological factors, such as body weight, age, health, sex of the subject, previous or concurrent therapeutic interventions, idiopathy of the patient, the route of administration, etc. (Para [0053]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have optimized the administration results in a plasma Cmax for the chemotherapeutic agent so that is less than about 100 ng/mL, as suggested by Hsia, since the administration results of the plasma Cmax would depend on the appropriate dosage amount administered to the subject.
Regarding claim 7, Surber discloses the method for treating lung cancer set forth above, wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than about 401 ng/mL (Fig.5).
However, Surber fails to explicitly disclose wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than about 40 ng/mL.
Hsia teaches that the quantity of therapeutic composition to be administered, according to unit dose, depends on effect desired. Hsia further recognizes that the actual dosage amount of the therapeutic composition administered to a subject is determined by physical and physiological factors, such as body weight, age, health, sex of the subject, previous or concurrent therapeutic interventions, idiopathy of the patient, the route of administration, etc. (Para [0053]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have optimized the administration results in a plasma Cmax for the chemotherapeutic agent so that is less than about 40 ng/mL, as suggested by Hsia, since the administration results of the plasma Cmax would depend on the appropriate dosage amount administered to the subject.
Regarding claim 8, Surber discloses the method for treating lung cancer set forth above, wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than about 401 ng/mL (Fig.5).
However, Surber fails to explicitly disclose wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than about 30 ng/mL.
Hsia teaches that the quantity of therapeutic composition to be administered, according to unit dose, depends on effect desired. Hsia further recognizes that the actual dosage amount of the therapeutic composition administered to a subject is determined by physical and physiological factors, such as body weight, age, health, sex of the subject, previous or concurrent therapeutic interventions, idiopathy of the patient, the route of administration, etc. (Para [0053]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have optimized the administration results in a plasma Cmax for the chemotherapeutic agent so that is less than about 30 ng/mL, as suggested by Hsia, since the administration results of the plasma Cmax would depend on the appropriate dosage amount administered to the subject.
Regarding claim 12, Surber discloses the method for treating lung cancer set forth above, wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than 15% of the plasma Cmax for the chemotherapeutic agent from systemic administration (Fig.5, Para [0695]).
However, Surber fails to explicitly disclose wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than 1% of the plasma Cmax for the chemotherapeutic agent from systemic administration.
Hsia teaches that the quantity of therapeutic composition to be administered, according to unit dose, depends on effect desired. Hsia further recognizes that the actual dosage amount of the therapeutic composition administered to a subject is determined by physical and physiological factors, such as body weight, age, health, sex of the subject, previous or concurrent therapeutic interventions, idiopathy of the patient, the route of administration etc. (Para [0053]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have optimized the administration results in a plasma Cmax for the chemotherapeutic agent so that is less than 1% of the plasma Cmax for the chemotherapeutic agent from systemic administration, as suggested by Hsia, since the administration results of the plasma Cmax would depend on the appropriate dosage amount administered to the subject.
Regarding claim 13, Surber discloses the method for treating lung cancer set forth above, wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than 15% of the plasma Cmax for the chemotherapeutic agent from systemic administration (Fig.5, Para [0695]).
However, Surber fails to explicitly disclose wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than 0.1% of the plasma Cmax for the chemotherapeutic agent from systemic administration.
Hsia teaches that the quantity of therapeutic composition to be administered, according to unit dose, depends on effect desired. Hsia further recognizes that the actual dosage amount of the therapeutic composition administered to a subject is determined by physical and physiological factors, such as body weight, age, health, sex of the subject, previous or concurrent therapeutic interventions, idiopathy of the patient, the route of administration etc. (Para [0053]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have optimized the administration results in a plasma Cmax for the chemotherapeutic agent so that is less than 0.1% of the plasma Cmax for the chemotherapeutic agent from systemic administration, as suggested by Hsia, since the administration results of the plasma Cmax would depend on the appropriate dosage amount administered to the subject.
Regarding claim 14, Surber discloses the method for treating lung cancer set forth above, wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than 15% of the plasma Cmax for the chemotherapeutic agent from systemic administration (Fig.5, Para [0695]).
However, Surber fails to explicitly disclose wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than 0.5% of the plasma Cmax for the chemotherapeutic agent from systemic administration.
Hsia teaches that the quantity of therapeutic composition to be administered, according to unit dose, depends on effect desired. Hsia further recognizes that the actual dosage amount of the therapeutic composition administered to a subject is determined by physical and physiological factors, such as body weight, age, health, sex of the subject, previous or concurrent therapeutic interventions, idiopathy of the patient, the route of administration etc. (Para [0053]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have optimized the administration results in a plasma Cmax for the chemotherapeutic agent so that is less than 0.5% of the plasma Cmax for the chemotherapeutic agent from systemic administration, as suggested by Hsia, since the administration results of the plasma Cmax would depend on the appropriate dosage amount administered to the subject.
Regarding claim 15, Surber discloses the method for treating lung cancer set forth above, wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than 15% of the plasma Cmax for the chemotherapeutic agent from systemic administration (Fig.5, Para [0695]).
However, Surber fails to explicitly disclose wherein the administration results in a plasma Cmax for the chemotherapeutic agent that is less than 0.05% of the plasma Cmax for the chemotherapeutic agent from systemic administration.
Hsia teaches that the quantity of therapeutic composition to be administered, according to unit dose, depends on effect desired. Hsia further recognizes that the actual dosage amount of the therapeutic composition administered to a subject is determined by physical and physiological factors, such as body weight, age, health, sex of the subject, previous or concurrent therapeutic interventions, idiopathy of the patient, the route of administration etc. (Para [0053]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have optimized the administration results in a plasma Cmax for the chemotherapeutic agent so that is less than 0.05% of the plasma Cmax for the chemotherapeutic agent from systemic administration, as suggested by Hsia, since the administration results of the plasma Cmax would depend on the appropriate dosage amount administered to the subject.
Regarding claim 16, Surber discloses the method for treating lung cancer set forth above, but Surber fails to expressly disclose wherein the liquid formulation further comprises dextrose, sodium chloride, potassium chloride, calcium chloride, sodium bicarbonate or combinations thereof.
Hsia teaches a liquid formulation further comprising dextrose, sodium chloride, potassium chloride, calcium chloride, sodium bicarbonate or combinations thereof (“sodium chloride” – Para [0052], “drug or therapeutic agent, may be dissolved or dispersed in a pharmaceutically acceptable carrier” – Para [0111]).
It would be obvious to one in the ordinary skill in the art, before the effective filing date of the applicant’s claimed invention to modify the liquid formulation disclosed by Surber to further comprise sodium chloride as taught by Hsia since sodium chloride is an aqueous solvent that can be used to dissolve the therapeutic medication in, optimizing the drug's properties for a safe and effective delivery to the lungs.
Regarding claim 17, Surber discloses the method for treating lung cancer set forth above, but Surber fails to expressly disclose wherein the liquid formulation further comprises saline solution.
Hsia teaches a liquid formulation further comprising saline solution (“saline” – Para [0052], “drug or therapeutic agent, may be dissolved or dispersed in a pharmaceutically acceptable carrier” – Para [0111]).
It would be obvious to one in the ordinary skill in the art, before the effective filing date of the applicant’s claimed invention to modify the liquid formulation disclosed by Surber to further comprise saline as taught by Hsia since saline is an aqueous solvent that can be used to dissolve the therapeutic medication in, optimizing the drug's properties for a safe and effective delivery to the lungs.
Regarding claim 18, Surber discloses the method for treating lung cancer set forth above, but Surber fails to expressly disclose wherein the liquid formulation further comprises Ringer’s solution.
Hsia teaches a liquid formulation further comprises Ringer's solution (“Ringer’s dextrose” – Para [0052], “drug or therapeutic agent, may be dissolved or dispersed in a pharmaceutically acceptable carrier” – Para [0111]).
It would be obvious to one in the ordinary skill in the art, before the effective filing date of the applicant’s claimed invention to modify the liquid formulation disclosed by Surber to further comprise Ringer’s solution as taught by Hsia since Ringer’s solution is an aqueous solvent that can be used to dissolve the therapeutic medication in, optimizing the drug's properties for a safe and effective delivery to the lungs.
Regarding claim 19, Surber discloses the method for treating lung cancer set forth above, but Surber fails to expressly disclose wherein the chemotherapeutic agent is vinblastine, vinorelbine, irinotecan, paclitaxel, docetaxel, epirubicin, doxorubicin, capecitabine, etoposide, topotecan, pemetrexed, carboplatin, fluorouracil, gemcitabine, oxaliplatin, cisplatin, trastuzumab, ramucirumab, bevacizumab or combinations thereof.
Hsia teaches a liquid formulation comprising a chemotherapeutic agent that is paclitaxel (“paclitaxel” – Para [0131]).
It would be obvious to one in the ordinary skill in the art, before the effective filing date of the applicant’s claimed invention to modify the liquid formulation disclosed by Surber to comprise a chemotherapeutic agent that is paclitaxel as taught by Hsia since paclitaxel is a compound that is administered in the treatment of cancer to kill cancer cells (Hsia, Para [0130]).
Regarding claim 20, Surber discloses the method for treating lung cancer set forth above, but Surber fails to expressly disclose wherein the chemotherapeutic agent is paclitaxel, cisplatin, levofloxacin or combinations thereof.
Hsia teaches a liquid formulation comprising a chemotherapeutic agent that is paclitaxel (“paclitaxel” – Para [0131]).
It would be obvious to one in the ordinary skill in the art, before the effective filing date of the applicant’s claimed invention to modify the liquid formulation disclosed by Surber to comprise a chemotherapeutic agent that is paclitaxel as taught by Hsia since paclitaxel is a compound that is administered in the treatment of cancer to kill cancer cells (Hsia, Para [0130]).
Conclusion
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/MARISSA TAYLOR/Examiner, Art Unit 3783
/BHISMA MEHTA/Supervisory Patent Examiner, Art Unit 3783