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 6 are objected to because of the following informalities: claims 1 recites that the biodegradable microparticles have: a Dv50 of 30 mm to 90 mm. However, the instant specification recites the Dv50 of 30 µm to 90 µm. Claim 6 recites a Dv50 of 50 mm to 80 mm, preferably 60 mm to 75 mm. However, the instant specification recites the Dv50 50 µm to 80 µm, preferably 60 µm to 75 µm. Appropriate correction is required.
Claims 3-6, 8 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim any of the preceding claims. See MPEP § 608.01(n). Accordingly, the claims 4-6, 8 cannot be further treated on the merits.
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 1-19 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.
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, claim 1 recites the broad recitation specific surface area of less than 0.50 m2/g, and the claim also recites preferably less than 0.40 m2/g 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.
In the present instance, claim 1 recites the broad recitation over 30 days or more, and the claim also recites and more preferably over 30 days to 200 days, or over 60 days or more, and preferably 60 to 200 days, or over 90 days or more, and preferably 90 to 200 days 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.
In the present instance, claim 4 recites the broad recitation have a drug loading of 11 to 14 w/w%, and the claim also recites and preferably 11.5 to 12.5 w/w% 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.
In the present instance, claim 6 recites the broad recitation a Dv50 of 50 mm to 80 mm, and the claim also recites preferably 60 mm to 75 mm 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.
In the present instance, claim 7 recites the broad recitation the somatostatin analogue is octreotide or pharmaceutically acceptable salt, and the claim also recites preferably wherein the somatostatin analogue is a pharmaceutically acceptable salt of octreotide selected from the group consisting of octreotide and octreotide pamoate 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.
In the present instance, claim 8 recites the broad recitation at least 50 w/w% of the PGLA, and the claim also recites preferably at least 85 w/w%, and more preferably 100 w/w% 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.
In the present instance, claim 9 recites the broad recitation at least 50 w/w% of the total, and the claim also recites preferably at least 75 w/w%, and more preferably at least 80 w/w% 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.
In the present instance, claim 10 recites the broad recitation release of less than 7% of the somatostatin analogue comprised therein over 5 hours, wherein said release is measured in vitro (at 37°C in 900mL of a pH4 100mM acetate buffer) according to the method described in the European Pharmacopoeia 10, 2.9.3., wherein said composition is tested in an amount equating to 30mg of the somatostatin analogue, and wherein said somatostatin analogue is preferably octreotide, and the claim also recites wherein the composition is preferably characterized by a release of the somatostatin analogue that fulfils the following test criteria: release of less than 3% of the somatostatin analogue comprised therein over 5 hours, wherein said release is measured in vitro (at 37°C in 900mL of a pH4 100mM acetate buffer) according to the method described in the European Pharmacopoeia 10, 2.9.3., wherein said composition is tested in an amount equating to 30mg of the somatostatin analogue, and wherein said somatostatin analogue is preferably octreotide, 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.
In the present instance, claim 11 recites the broad recitation: a concentration of 100mg/mL to 500 mg/mL, and the claim also recites particularly preferably, 100 mg/mL to 375 mg/mL, and most preferably 125 mg/mL to 375 mg/mL 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.
In the present instance, claim 14 recites the broad recitation a somatostatin analogue, or a pharmaceutically acceptable salt thereof, and the claim also recites preferably the disease is from the group consisting of autosomal dominant polycystic kidney disease, Cushing's disease, polycystic liver disease, acromegaly, gigantism, TSH-secreting pituitary adenomas, carcinoid syndrome, vasoactive intestinal peptide tumors, and neuroendocrine neoplasms including neuroendocrine tumors including gastro-entero-pancreatic neuroendocrine tumors, and preferably is selected from acromegaly and gastro-entero-pancreatic neuroendocrine tumors 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.
In the present instance, claim 17 recites the broad recitation administered to a patient, and the claim also recites preferably via intra-muscular or subcutaneous injection 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.
In the present instance, claim 19 recites the broad recitation comprises at least 50 w/w%, and the claim also recites preferably 85 w/w% and most preferably 100 w/w% 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.
Claims 2, 3, 5, 12, 13, 15 and 18 are dependent from indefinite claims and are therefore also indefinite.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over the combined disclosures of Ahlheim et al (US 2010/0266704 A1 hereafter Ahlheim) in view of Mehta et al (Biodegradable microspheres as depot system for parenteral delivery of peptide drugs, Journal of Controlled Release, 29, 1994, 375-384 hereafter Mehta).
Ahlheim discloses a pharmaceutical dosage form comprising biodegradable polymer microparticles comprising a somatostatin analogue and wherein the biodegradable polymer is PLGA [abstract]. The PGLA has a molar ratio of lactide to glycolide from 80:20 to 90:10 [0009]; with an inherent viscosity from 0.2 to 0.4 dl/g [0009]; a drug loading from 10-15 w/w% [026] and a diameter up to 90 microns [0033]. Specific PLGA polymers have a ratio of 85:15 with an inherent velocity from 0.26-0.54 dL/g [Table 1]. Microspheres can have polymer concentration above 50% [Table 2]. The somatostatin analogue is octreotide pamoate [claims]. The composition is used as a medicament and is sterilized via radiation [0028, claims]. The composition is applied in a method of treating a disease including vasoactive intestinal peptide tumors [0002]. The composition provides sustained release up to 90 days with 30 mg of delivery of the octreotide [0011-0012]. The formulation is an injectable formulation [Examples]. A kit is disclosed comprising a vial with the composition, a vehicle for reconstitution and syringe for injection [Example 4]. The formulation is formed by a method comprising preparing an organic phase with a PLGA polymer and a solvent, preparing an aqueous phase comprising a PVA stabilizer, mixing the organic and aqueous phase, removing the solvents and drying the polymer microparticles [Examples].
While disclosing a sustained release injectable drug depot comprising microspheres comprising a drug and PLGA, the reference is silent to the specific surface area of the microspheres. The use of specific polymers for injectable drug loading is known in the art as seen in the Mehta reference.
Mehta discloses a biodegradable drug depot comprising polymers of lactic and glycolide acid (abstract). The polymers are blended with an active agent and formed into microspheres where the specific surface area of the microspheres is 0.3 m2/g (Table 1). The formulation is applied for parenteral delivery (abstract). It would have been obvious to include the specific biodegradable polymer into the formulation of Ahlheim as they solve the same problem.
Regarding the specific release kinetics of the formulation, it is the position of the Examiner that such limitations do not distinguish over the prior art. The prior art discloses a drug depot of the same drug compound, in the same concentration, polymers and formulation, delivered the same way, for the same length of time. The Office does not have the facilities for examining and comparing applicants’ product with the product of the prior art in order to establish that the product of the prior art does not possess the same material structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the claimed products are functionally different than those taught by the prior art and to establish patentable differences. See Ex parte Phillips, 28 U.S.P.Q.2d 1302, 1303 (PTO Bd. Pat. App. & Int. 1993), Ex parte Gray, 10 USPQ2d 1922, 1923 (PTO Bd. Pat. App. & Int.) and In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977).
With these aspects in mind, it would have been obvious to combine the prior art with an expected result of stable microsphere formulation useful in sustained drug delivery and treatment of intestinal peptide tumors. It would have been obvious to include the polymers of Mehta into the formulation of Ahlheim as they have similar structure and application. One of ordinary skill in the art would have been motivated to include the polymers as they solve the same problem and to form a stable injectable depot formulation.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICAH PAUL YOUNG whose telephone number is (571)272-0608. The examiner can normally be reached Monday through Friday, 9:00 am to 5:30 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 5712720616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICAH PAUL YOUNG/Primary Examiner, Art Unit 1618
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