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 .
Status of the Claims
Per Applicant’s amendment to the claims, submitted on 01/06/2026, claims 1, 3-4, and 9-11 are amended, and claim 21 is newly added. Currently, claims 1-17 and 21 are pending in the instant application.
Claim Objections – Necessitated by Amendment
Applicant is advised that should claim 9 be found allowable, claim 10 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). In the case of the instant claims, claims 9 and 10 are verbatim identical.
Claim 1 is objected to because of the following informalities: Grammar. Currently, the instant claim recites the following: “A pharmaceutical composition consists of” (underlined for emphasis). The recitation should be amended for grammatical clarity (i.e., “A pharmaceutical composition consisting of”) Appropriate correction is required.
Claim 6 is objected to because of the following informalities: Wording. The instant claim recites “wherein the cyclodextrin solubilizer includes said hydroxypropyl-B-cyclodextrin” (underlined for emphasis). As the parent claim already defines the cyclodextrin solubilizer as either HPBCD or MBCD, the word “includes” lacks clarity. It is recommended that Applicant chooses another term, such as “is” to clarify that the instant claim is limiting the cyclodextrin solubilizer to HPBCD.
Claim 7 is objected to because of the following informalities: Wording. The instant claim recites “wherein the cyclodextrin solubilizer includes said hydroxypropyl-B-cyclodextrin” (underlined for emphasis). As the parent claim already defines the cyclodextrin solubilizer as either HPBCD or MBCD, the word “includes” lacks clarity. It is recommended that Applicant chooses another term, such as “is” to clarify that the instant claim is limiting the cyclodextrin solubilizer to HPBCD.
Claim 8 is objected to because of the following informalities: Wording. The instant claim recites “wherein the cyclodextrin solubilizer includes said hydroxypropyl-B-cyclodextrin” (underlined for emphasis). As the parent claim already defines the cyclodextrin solubilizer as either HPBCD or MBCD, the word “includes” lacks clarity. It is recommended that Applicant chooses another term, such as “is” to clarify that the instant claim is limiting the cyclodextrin solubilizer to HPBCD.
Claim 9 is objected to because of the following informalities: Wording. The instant claim recites “the types of cyclodextrin solubilizer include said hydroxypropyl-B-cyclodextrin” (underlined for emphasis). As the parent claim already defines the cyclodextrin solubilizer as either HPBCD or MBCD, the underlined portion of the claim lacks clarity. It is recommended that Applicant amends the limitation to clarify that the instant claim is limiting the cyclodextrin solubilizer to HPBCD (i.e., wherein the cyclodextrin solubilizer is HPBCD, etc.).
Claim 10 is objected to because of the following informalities: Wording. The instant claim recites “the types of cyclodextrin solubilizer include said hydroxypropyl-B-cyclodextrin” (underlined for emphasis). As the parent claim already defines the cyclodextrin solubilizer as either HPBCD or MBCD, the underlined portion of the claim lacks clarity. It is recommended that Applicant amends the limitation to clarify that the instant claim is limiting the cyclodextrin solubilizer to HPBCD (i.e., wherein the cyclodextrin solubilizer is HPBCD, etc.).
Claim 11 is objected to because of the following informalities: Wording. The instant claim recites “the types of cyclodextrin solubilizer include said hydroxypropyl-B-cyclodextrin” (underlined for emphasis). As the parent claim already defines the cyclodextrin solubilizer as either HPBCD or MBCD, the underlined portion of the claim lacks clarity. It is recommended that Applicant amends the limitation to clarify that the instant claim is limiting the cyclodextrin solubilizer to HPBCD (i.e., wherein the cyclodextrin solubilizer is HPBCD, etc.).
Claim Rejections - 35 USC § 112 Second Paragraph – Necessitated by Amendment
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 1-3, 9-11-17 and 21 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 is indefinite for reciting the phrase “wherein said pharmaceutical composition comprises 20 mg/mL of said pazopanib hydrochloride” (underlined for emphasis), because a person of ordinary skill in the art would not reasonable be able to understand the metes and bounds of the claim. The recitation of the word “comprises” provides improper antecedence to the earlier established limitation of the claim which recites a pharmaceutical composition consisting of the recited components. Applicant is recommended to change the wording of the limitation (i.e., wherein said pazopanib hydrochloride is present at a concentration of 20 mg/mL, etc.)
Claim 2 is indefinite for reciting the phrase “the pharmaceutical composition further comprises an additive”, because a person of ordinary skill in the art would not reasonable be able to understand the metes and bounds of the claim. Newly amended parent claim 1 recites a composition consisting of the recited components, including an optional additive. The use of the term “further comprising” provides improper antecedence to claim 1. If Applicant’s intent is to include the optional additive recited in claim 1, the limitation must be revised.
Claim 3 is indefinite for reciting the phrase “wherein, the cyclodextrin solubilizer is said B-cyclodextrin derivative”, because a person of ordinary skill in the art would not reasonable be able to understand the metes and bounds of the claim. Parent claim 1 recites a composition consisting of a cyclodextrin solubilizer, wherein the cyclodextrin solubilizer is a B-cyclodextrin derivative. The indicated limitation of claim 3 does not further limit the composition of claim 1, but simply reiterates an existing limitation of the claim.
Claim 9 is indefinite for reciting a composition “consisting of: pazopanib, a cyclodextrin solubilizer, and a solvent” because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Parent claim 1 recites a composition consisting of four components:
Pazopanib, wherein the pazopanib is pazopanib HCl
A cyclodextrin solubilizer, wherein the cyclodextrin solubilizer is a B-cyclodextrin derivative which is HPBCD or MBCD
A solvent, wherein the solvent is water free of oxygen
A pH regulator selected from one or more of glycerol, propylene glycol, poloxamer, sucrose, mannitol, glucose, sodium chloride, and amino acids
By reciting “pazopanib, a cyclodextrin solubilizer, and a solvent” in the instant claim, Applicant has created limitations that are now broader than the limitations of the parent the claim because: 1) the recited components are no longer limited to the species recited in claim 1; and 2) the instant claim no longer includes the recited pH regulator of claim 1. This rejection may be overcome by amending the instant claim to remove the recitation regarding the composition consisting of pazopanib, solubilizer, and solvent. Applicant is reminded that limitations of the parent claim do not need to be restated if they are not being further limited by the instant claim. In the case of the instant claim, only the recitation regarding the concentration of solubilizer and selection of HPBCD are further limiting of claim 1.
Claim 10 is indefinite for reciting a composition “consisting of: pazopanib, a cyclodextrin solubilizer, and a solvent” because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Parent claim 1 recites a composition consisting of four components:
Pazopanib, wherein the pazopanib is pazopanib HCl
A cyclodextrin solubilizer, wherein the cyclodextrin solubilizer is a B-cyclodextrin derivative which is HPBCD or MBCD
A solvent, wherein the solvent is water free of oxygen
A pH regulator
Optionally, an additive selected from one or more of glycerol, propylene glycol, poloxamer, sucrose, mannitol, glucose, sodium chloride, and amino acids
By reciting “pazopanib, a cyclodextrin solubilizer, and a solvent” in the instant claim, Applicant has created limitations that are now broader than the limitations of the parent the claim because: 1) the recited components are no longer limited to the species recited in claim 1; and 2) the instant claim no longer includes the recited pH regulator of claim 1. This rejection may be overcome by amending the instant claim to remove the recitation regarding the composition consisting of pazopanib, solubilizer, and solvent. Applicant is reminded that limitations of the parent claim do not need to be restated if they are not being further limited by the instant claim. In the case of the instant claim, only the recitation regarding the concentration of solubilizer and selection of HPBCD are further limiting of claim 1.
Claim 11 is indefinite for reciting a composition “consisting of: pazopanib, a cyclodextrin solubilizer, and a solvent” because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Parent claim 1 recites a composition consisting of four components:
Pazopanib, wherein the pazopanib is pazopanib HCl
A cyclodextrin solubilizer, wherein the cyclodextrin solubilizer is a B-cyclodextrin derivative which is HPBCD or MBCD
A solvent, wherein the solvent is water free of oxygen
A pH regulator
Optionally, an additive selected from one or more of glycerol, propylene glycol, poloxamer, sucrose, mannitol, glucose, sodium chloride, and amino acids
By reciting “pazopanib, a cyclodextrin solubilizer, and a solvent” in the instant claim, Applicant has created limitations that are now broader than the limitations of the parent the claim because: 1) the recited components are no longer limited to the species recited in claim 1; and 2) the instant claim no longer includes the recited pH regulator of claim 1. This rejection may be overcome by amending the instant claim to remove the recitation regarding the composition consisting of pazopanib, solubilizer, and solvent. Applicant is reminded that limitations of the parent claim do not need to be restated if they are not being further limited by the instant claim. In the case of the instant claim, only the recitation regarding the concentration of solubilizer and selection of HPBCD are further limiting of claim 1.
Claim 21 is indefinite for reciting a composition “consisting of: pazopanib; a cyclodextrin solubilizer; a solvent; a pH regulator” because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Parent claim 1 recites a composition consisting of four components:
Pazopanib, wherein the pazopanib is pazopanib HCl
A cyclodextrin solubilizer, wherein the cyclodextrin solubilizer is a B-cyclodextrin derivative which is HPBCD or MBCD
A solvent, wherein the solvent is water free of oxygen
A pH regulator
Optionally, an additive selected from one or more of glycerol, propylene glycol, poloxamer, sucrose, mannitol, glucose, sodium chloride, and amino acids
By reciting “pazopanib; a cyclodextrin solubilizer; a solvent; a pH regulator” in the instant claim, Applicant has created limitations that are now broader than the limitations of the parent claim because the components are no longer limited to the species recited in claim 1. This rejection may be overcome by amending the instant claim to remove the recitation regarding the composition consisting of pazopanib, solubilizer, and solvent. Applicant is reminded that limitations of the parent claim do not need to be restated if they are not being further limited by the instant claim. In the case of the instant claim, only the recitation regarding the selection of the additive is further limiting of claim 1 (i.e., wherein the additive is present and selected from one of glucose or sodium chloride).
Claim 12 is indefinite for reciting the phrase “comprising mixing the pharmaceutical composition as defined in claim 1” because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The recitation of the claim is currently ambiguous. As currently recited, the claim can be construed as referring back to a mixing method defined in claim 1, which would be erroneous due to claim 1 being a composition claim. Accordingly, this would provide improper antecedence to claim 1. Furthermore, the recitation of “mixing the pharmaceutical composition” does not provide a person of ordinary skill in the art with structural actionable steps with which to carry out the method. It is recommended that Applicant revise the claim, both through a re-wording of the method, and incorporation of the steps outlined in at least claims 13 and 14 into the instant claim, as these claims provide a specified action (i.e., stirring) and the order in which the components are combined.
Claim 13 is indefinite for reciting the phrase “The method for preparing the pharmaceutical composition as defined in claim 12” because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The current recitation of the instant claim is grammatically ambiguous when referring back to parent claim 12. As currently recited, the claim could be construed to be referencing a “composition as defined in claim 12” rather than the method. It is recommended that Applicant amend the claim to clearer language (i.e., “the method of claim 12 wherein…”, etc.).
Claims 14-17 are indefinite for reciting the phrase “The method for preparing the pharmaceutical composition as defined in claim 13” because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The current recitation of the instant claim is grammatically ambiguous when referring back to parent claim 13. As currently recited, the claim could be construed to be referencing a “composition as defined in claim 12” rather than the method. It is recommended that Applicant amend the claims to clearer language (i.e., “the method of claim 12 wherein…”, etc.).
Claim Rejections - 35 USC § 103 – Withdrawn
Rejections of claims 1-17:
In light of Applicant’s amendment to the claims, the rejections are hereby withdrawn. Applicant has amended claim 1 such that the claim now recites a composition “consisting of” the recited components. The teachings of the Horvath prior art are directed towards pazopanib compositions comprising polyvinylpyrrolidone (PVP) as solubilizer. The claims as recited now exclude components which are not expressly recited.
Allowable Subject Matter
While the claims are not currently allowable (see Objections and outstanding rejections), it appears that the prior art does not teach or reasonably suggest the 20 mg/ml pazopanib hydrochloride composition of the instant claims consisting of the recited elements. The closest prior art are Horvath (previously referenced) and Wu (US 20230026808 A1).
The teachings of Horvath are drawn to compositions comprising pazopanib HCl. The compositions of Horvath are generally comprised of pazopanib HCl, a cyclodextrin as a complexing agent, polyvinylpyrrolidone as a solubilizing agent, pH adjusting agents, and water as a solvent. A general summary of exemplary formulations by Horvath are provided below (specification [0251]-[0262]):
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Formulations containing the indicated components were prepared at 60, 50, and 36 mg/ml of pazopanib. As the teachings of Horvath appear to be drawn to pazopanib compositions of concentration different to the instant claims and using components outside the scope the claimed compositions, Horvath cannot be considered to obviating matter.
Wu teaches pazopanib compositions and uses thereof for the treatment of ischemia reperfusion injury. Of particular relevance to the instant invention is an exemplary formulation containing 5 mg/ml pazopanib hydrochloride and 200 mg/ml HPBCD, using water for injection as a solvent (specification [0202])1. Wu makes mention that the formulation may be diluted in saline or a 5% glucose solution for the purpose of creating a final composition for infusion administration (specification [0202])2. In the case of the aforementioned example, a 10 mL composition is combined with 24 mL of saline or glucose solution, resulting in a final composition having a pazopanib concentration of 0.147 mg/mL and HPBCD concentration of 58.8 mg/mL. While the teachings of Wu include a composition comprising pazopanib HCl, a cyclodextrin, solvent, and optional additive, Wu makes no suggestion of pH adjustment, water free of oxygen, or the scaling of pazopanib HCl to a higher concentration such as the 20 mg/ml of the claimed composition.
Conclusion
Claims 1-17, and 21 are rejected.
Claims 1 and 6-11 are objected.
THIS ACTION IS MADE FINAL. 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.
/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “A non-limiting formulation comprises pazopanib hydrochloride solubilized in hydroxypropyl betadex (HPB) and water for injection, prepared as an intravenous (IV) formulation. Each mL contains 5 mg of pazopanib hydrochloride and is solubilized with 200 mg of Hydroxypropyl Betadex USP and Water for Injection USP.”
2 “The contents of the vial are diluted into 24 mL 0.9% Sodium Chloride Injection, USP (Normal Saline), or 5% glucose solution prior to infusion. The contents of one vial will supply 30 mg of pazopanib hydrochloride. “
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