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 .
Status of the Claims
Claims 1-22 are pending and under current examination.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: Specifically, the equation for “HIR” recited in claim 2, line 2 “(m”*(L)/(VD)*(10^-6)” lacks antecedent basis. The specification describes an equation for HIR of:
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The difference between claim 2 and the equation in the specification is that the parameter “L” is squared in the specification but not in the equation recited in claim 2. Correction or clarification is requested.
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 1-22 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.
Both of claims 1 and 19 recite the term “glycolide-based”. This term renders the claims indefinite because it is unclear to what extent the copolymer must resemble glycolide to fall within the scope of the term “glycolide-based”.
Claim 1 recites “including” in line 6. This renders the claim indefinite because in this instance the word “including” could reasonably be interpreted as indicating the text that follows is exemplary. As such one of ordinary skill cannot unambiguously ascertain whether the language following “including” further limits the claimed invention.
Claim 1 recites “a first uterus location”, implying that there is also a second uterus location in the claimed method; however, this is not expressly recited in the claim. For this reason, one of ordinary skill cannot determine whether the claim also requires a additional uterine locations in addition to the first location.
Claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness concerns outlined 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 6-9 and 11-18 are rejected under 35 U.S.C. 103 as being unpatentable over McIntyre et al. (US 2006/0251581; publication date: 11/09/2006) in view of Shalgi et al. (US 2018/0043001; publication date: 02/15/2018) and further in view of Canifax et al. (US 20120150105; publication date: 06/14/2012), and Trollsas et al. (US 2022/0031606; publication date: 02/03/2022).
With regard to claim 1, McIntyre discloses an injectable uterine fibroid treatment formulation comprising a treatment agent in an amount effective to cause shrinkage or elimination of the uterine fibroid wherein the composition is, inter alia, a high-viscosity fluid (abstract). The method of treatment is minimally invasive (0010), results in improved retention of the active agents within the uterine fibroid (0011) that are injected into the uterine fibroid using a hollow delivery channel such as a needle or canula associated with a specially designed syringe (0068). The injection may be laparoscopic, trans-abdominal, or hysteroscopic and trans-vaginal (0078, 0079). The agents may be oral contraceptives and GnRH agonists or chemical agents that cause death or shrinkage of the fibroid tissue (0021, 0022).
Thus, McIntyre discloses a method for treating uterine fibroids in a subject in need thereof, comprising using a needle syringe containing a liquid, viscous active agent formulation and dispensing a total volume of the composition into a uterus to produce an efficacious outcome for treating fibroids. A unit volume would necessarily be dispensed to a first uterus location using the needle syringe according to McIntyre’s method. McIntyre discloses further that uterine fibroids (also called leiomyomas) are common non-cancerous smooth muscle tumors (i.e. overgrowth of smooth muscle) of the uterus that can cause various uncomfortable symptoms in some women (0003). However, McIntyre does not expressly disclose a “first uterus location”, or imply greater than one uterus location is being treated, as do the instant claims.
Shalgi discloses that uterine fibroids can occur as a plurality of fibroids (0075).
It would have been prima facie obvious to inject the first of many fibroids in McIntyre’s method in the case that the patient had greater than one fibroid in need of treatment, in order to treat each of the areas in need of treatment.
McIntyre also does not disclose administering a cytotoxic and/or cytostatic drug in a glycolide-based bioabsorbable copolymer and a water soluble solvent capable of dissolving the drug and copolymer.
Canifax discloses that anti-proliferative agents such as rapamycin (cytostatic agents) or docetaxel or paclitaxel (cytotoxic agents) delivered to the treatment location can effectively treat uterine fibroids (abstract, 0010, table 1, 0100).
It would have been prima facie obvious to also deliver cytotoxic agents or cytostatic agents directly to the uterine fibroid in McIntyre’s method. One having ordinary skill would have been motivated to do so in order to cause shrinkage or death of the fibroid, a goal stated by McIntyre and would have had reasonable expectation of success because these agents have been shown to be effective in this context (Canifax).
Neither McIntyre nor Canifax disclose a formulation comprising the cytotoxic or cytostatic drug and a glycolide-based bioabsorbable copolymer, and a water soluble solvent capable of dissolving the drug and copolymer.
Trollsas discloses a minimally invasive treatment of benign prostatic hyperplasia (BPH) tissue by a system that directly injects into the affected area (the prostate) a sustained release formulation that comprises PLGA (poly(lactic-co-glycolic) acid; a glycolide-based polymer) a cytotoxic or cytostatic drug such as paclitaxel or sirolimus, respectively, releasing drug for a period between 14 days and 12 months (abstract, 0028, 0029). Both the drugs and the PLGA are dissolved in the NMP (0059, 0060). Trollsas also factors the viscosity of the polymer (0044, 0047) and describes the composition as being able to pass through a 16G needle or larger and having a gel-like viscosity (0060, 0061). Trollsas describes successful localized injection and sustained delivery specifically to the affected area when the composition comprises PLGA, sirolimus or paclitaxel, and the solvent N-methyl pyrrolidone (NMP; Table 1, page 4 and 0085 – 0102, which detail successful BPH treatment in an animal model). Trollsas discloses further that BPH involves pathologic hyperproliferation of smooth muscle in the prostate (0003).
It would have been prima facie obvious to administer the composition containing PLGA and paclitaxel or the mTOR inhibitor, sirolimus, in NMP via injection into a uterine fibroid as described by McIntyre. The artisan of ordinary skill would have been motivated to do so and had a reasonable expectation of success because this formulation already had been demonstrated to provide local sustained delivery of drug to a lesion formed by hyperproliferation of smooth muscle cells, causing shrinkage of the smooth muscle tumor. One having ordinary skill would have reasonably expected the uterine fibroid smooth muscle tumor to respond similarly to the prostate smooth muscle overgrowth.
With regard to claim 3, it would have been obvious to treat each of the fibroids in need of treatment with the composition above, i.e. administer a unit volume, only as much as needed, to a second target tissue of the uterus using the same apparatus that was effective for delivering the first dose.
With regard to claim 6, McIntyre discloses that the volume of injection will vary depending upon the size of the fibroid to be treated and will typically range from 1.0 to 10.0 mL per injection (0076). This would give one of ordinary skill a starting point to optimize dose/volume of the injection to deliver and effective amount of the composition disclosed by Trollsas. See MPEP 2144.05.
With regard to claims 7, 15, and 17, Trollsas discloses anywhere from 1 to 20% of drug in the formulation in example compositions (table 1, page 4). This would give the artisan of ordinary skill a starting point to optimize dose for effective treatment of uterine fibroids (see MPEP 2144.05).
With regard to claims 8, 9, and 17, as noted above, the drug used in Trollsas’s composition is paclitaxel and/or sirolimus.
With regard to claim 11, as noted above, the composition disclosed by McIntyre may be used to deliver GnRH or birth control such as levonogestrel (0029).
With regard to claim 12, the PLGA used in example compositions ranges from 85:15 to 50:50 LA:GA monomer ratio (table 1, page 4).
With regard to claims 13 and 14, as noted above, the composition contains PLGA and NMP.
With regard to claim 16, Trollsas discloses the SRF, once located at the target tissue, may release 1-10%, or 11-50% of the drug load in less than 24 hours (0040). This range overlaps with the range recited in the instant claims and would give the person of ordinary skill a starting point to optimize the initial effective concentration that is achieved shortly after the formulation is deposited in the region of the fibroid. See MPEP 2144.05.
With regard to claim 18, as noted above it would maximize efficiency to deliver each dose of the composition from a single needle syringe device, and therefore it would have been obvious to contain the total volume required for multiple doses within the syringe.
Claims 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over McIntyre et al. (US 2006/0251581; publication date: 11/09/2006) in view of Shalgi et al. (US 2018/0043001; publication date: 02/15/2018) and further in view of Canifax et al. (US 20120150105; publication date: 06/14/2012), and Trollsas et al. (US 2022/0031606; publication date: 02/03/2022) as applied to claims 1, 3, 6-9 and 11-18 above, and further in view of Pui et al. (US20200113820; publication date: 04/16/2020; cited in the IDS filed 08/08/2023).
With regard to claims 4 and 5, the relevant disclosures of McIntyre, Shalgi, Canifax, and Trollsas are set forth above and render obvious a method of treating uterine fibroids in a subject in need thereof, comprising using an apparatus comprising a needle syringe containing a composition comprising a cytotoxic or cytostatic drug, a glycolide-based bioabsorbable copolymer, and a solvent capable of dissolving the drug and copolymer and dispensing a plurality of unit volumes, v, of the composition at a respective plurality of different locations in the uterus using the needle syringe, and wherein the plurality of unit volumes is equal to a total volume for treating uterine fibroids. None of these references disclose that the injection volume is a plurality, n, of the no more than a unit volume, v, injected into the uterus to treat a fibroid having a corresponding n fibroid locations, wherein n is related to a fibroid volume (FV) as n = FV/(75*v), wherein the sum of the plurality of the n of the unit volumes v is a total volume for treatment of the fibroid.
Pui, in the analogous art of paclitaxel injections directly into a tumor to decrease the size of the tumor (abstract), discloses that the amount of the injection liquid used depends upon the size or volume of the tumor (0069).
Thus, one having ordinary skill would have recognized that the volume of formulation containing the drug in the method of McIntyre/Shalgi/Canifax/Trollsas would be proportional to the size of the fibroid to be treated. As described in the rejection above, it would have been prima facie obvious to administer multiple doses from the same syringe in a patient having multiple fibroids for efficiency. In view of the foregoing, it also follows that it would have been obvious that the total volume in the syringe would be related to the number of fibroids as well as each of their volumes. It would have been merely routine for one of ordinary skill to optimize the formulation volume (total volume for n injections and volume for each individual injection) based upon the volume of each fibroid to be treated. This is consistent with the goal Trollsas’s goal of minimizing side effects and reduce exposure of surrounding tissue to the drug (0009, 0055). See MPEP 2144.05(II): Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
With regard to claim 5, as noted in the rejection above, often a patient has greater than one fibroid in need of treatment. It would have been obvious to determine the number of fibroids requiring shrinkage, and based upon the volume of the fibroid, determining the volume of the formulation containing drug to administer to achieve shrinkage. McIntyre discloses that the volume of injection will vary depending on for example the size of the fibroid and that a range of from 1.0 to 10.0 mL per injection would be typical (0076). This would give one of ordinary skill a starting point to optimize the volume per fibroid (i.e. per injection) and as discussed above, it would have been obvious to inject each dose from a single syringe filled with the total required volume for all doses for the sake of efficiency and reduced invasiveness, as fewer injections would be less invasive. Therefore the number “n” does not patentably define over the cited prior art because “n” is simply however many fibroids are in need of treatment, and the volumes claimed overlap with the range for volume of injection disclosed by McIntyre. See MPEP 2144.05 regarding the obviousness of overlapping ranges.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over McIntyre et al. (US 2006/0251581; publication date: 11/09/2006) in view of Shalgi et al. (US 2018/0043001; publication date: 02/15/2018) and further in view of Canifax et al. (US 20120150105; publication date: 06/14/2012), and Trollsas et al. (US 2022/0031606; publication date: 02/03/2022) as applied to claims 1, 3, 6-9 and 11-18 above, and further in view of Palheta et al (Radiol Bras 56(2):86-94; publication date: March/April 2023).
The relevant disclosures of McIntyre, Shalgi, Canifax, and Trollsas are set forth above. McIntyre discloses laparoscopic or hysteroscopic injection; however, none of these references disclose measuring the uterus volume or weight by ultrasound imaging.
Palheta discloses that ultrasound for determining uterine volume is extremely useful in surgical planning for treatment of fibroids (figures and page 88, paragraph bridging left and right columns).
It would have been prima facie obvious to determine the uterine volume in the method of McIntyre/Shalgi/Canifax/Trollsas. The skilled artisan would have been motivated to do so in order to provide further information regarding the size and location of the fibroids relative to the whole uterus and would have had reasonable expectation of success because this was a routine step in fibroid assessment/surgical planning as of the instant effective filing date.
Claims 2, 19, 20 are rejected under 35 U.S.C. 103 as being unpatentable over McIntyre et al. (US 2006/0251581; publication date: 11/09/2006) in view of Shalgi et al. (US 2018/0043001; publication date: 02/15/2018) and further in view of Canifax et al. (US 20120150105; publication date: 06/14/2012), and Trollsas et al. (US 2022/0031606; publication date: 02/03/2022) as applied to claims 1, 3, 6-9 and 11-18 above, and further in view of Beebe (US20110073613; publication date: 03/31/2011).
With regard to claims 2 and 19, the relevant disclosures of McIntyre, Shalgi, Canifax, and Trollsas are set forth above and render obvious a method of treating uterine fibroids in a subject in need thereof, comprising using an apparatus comprising a needle syringe containing a composition comprising a cytotoxic or cytostatic drug, a glycolide-based bioabsorbable copolymer, and a solvent capable of dissolving the drug and copolymer and dispensing a plurality of unit volumes, v, of the composition at a respective plurality of different locations in the uterus using the needle syringe, and wherein the plurality of unit volumes is equal to a total volume for treating uterine fibroids. None of these references disclose a range in “H-injectate rating (HIR)” value as recited in the instant claims, or more specifically, wherein the composition has an absolute viscosity, µ, and the needle syringe has a needle length L with inner diameter D; wherein a unit volume is from 0.05 ml to 0.2 ml; and wherein the apparatus has a HIR of between 10 to 400 or 30 to 300 and HIR is defined as:
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Beebe discloses that accurate, precise dispensation of a liquid from a syringe-type dispenser depends on, inter alia, the volume being dispensed, the viscosity of the formulation, the length and inside diameter of the barrel [of the device] (0012). Thus, it was known in the art at the time of filing that there was a relationship among the factors in the instant equation for “HIR” and ease/accuracy of dispensation of a fluid. It would have been merely routine for one of ordinary skill to determine the interdependency and one having ordinary skill would have been motivated to determine a range in optimal parameters for dispensation of the fluid with consistent accurately at the target location in the method of McIntyre/Shalgi/Canifax/Trollsas. For this reason, the examiner does not consider the range in “HIR” required by the instant claims to patentably define over the cited prior art.
With regard to claim 20, as noted in the rejection above, Trollsas discloses either or both of paclitaxel and sirolimus may be delivered in the formulation.
Claims 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over McIntyre et al. (US 2006/0251581; publication date: 11/09/2006) in view of Shalgi et al. (US 2018/0043001; publication date: 02/15/2018) and further in view of Canifax et al. (US 20120150105; publication date: 06/14/2012), and Trollsas et al. (US 2022/0031606; publication date: 02/03/2022) and Beebe (US20110073613; publication date: 03/31/2011) as applied to claims 1-3, 6-9 and 11-20 above, and further in view of Pui et al. (US20200113820; publication date: 04/16/2020; cited in the IDS filed 08/08/2023).
With regard to claims 21 and 22, the relevant disclosures of McIntyre, Shalgi, Canifax, Trollsas, and Beebe are set forth above and render obvious a method of treating uterine fibroids in a subject in need thereof, comprising using an apparatus comprising a needle syringe containing a composition comprising a cytotoxic or cytostatic drug, a glycolide-based bioabsorbable copolymer, and a solvent capable of dissolving the drug and copolymer and dispensing a plurality of unit volumes, v, of the composition at a respective plurality of different locations in the uterus using the needle syringe, and wherein the plurality of unit volumes is equal to a total volume for treating uterine fibroids. None of these references disclose that the injection volume is a plurality, n, of the no more than a unit volume, v, injected into the uterus to treat a fibroid having a corresponding n fibroid locations, wherein n is related to a fibroid volume (FV) as n = FV/(75*v), wherein the sum of the plurality of the n of the unit volumes v is a total volume for treatment of the fibroid.
Pui, in the analogous art of paclitaxel injections directly into a tumor to decrease the size of the tumor (abstract), discloses that the amount of the injection liquid used depends upon the size or volume of the tumor (0069).
Thus, one having ordinary skill would have recognized that the volume of formulation containing the drug in the method of McIntyre/Shalgi/Canifax/Trollsas would be proportional to the size of the fibroid to be treated. As described in the rejection above, it would have been prima facie obvious to administer multiple doses from the same syringe in a patient having multiple fibroids for efficiency. In view of the foregoing, it also follows that it would have been obvious that the total volume in the syringe would be related to the number of fibroids as well as each of their volumes. It would have been merely routine for one of ordinary skill to optimize the formulation volume (total volume for n injections and volume for each individual injection) based upon the volume of each fibroid to be treated. This is consistent with the goal Trollsas’s goal of minimizing side effects and reduce exposure of surrounding tissue to the drug (0009, 0055). See MPEP 2144.05(II): Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Conclusion
No claims are allowed.
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/KATHERINE PEEBLES/ Primary Examiner, Art Unit 1617