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 Status
The preliminary amendment filed March 29, 2023 has been entered. Claims 1-9 are canceled. Claims 10-29 are new. Thus, claims 10-29 as amended are examined on the merits herein.
Claim Objections
Claims 10, 12, 14 and 16 are objected to because of the following informalities:
Claim 10, line 2, recites “which formulation comprises” which is clearly missing the article “the” immediately before the word “formulation”. Thus, to promote clarity the Examiner suggests inserting the word “the” immediately before “formulation” as discussed above.
Claim 12, lines 2-3, recite “endosperms of palm and or coconut plants” and is clearly missing the forward slash (i.e. “/”) between the recitation of “and or”. Thus, to promote clarity the Examiner suggests inserting the forward slash (i.e. “/”) between the recitation of “and or” in line 3 of claim 12.
Claim 14, line 3, recites “capric (C10) acids)” which recites a superfluous right parathesis immediately after the recitation “acids”. Thus, to promote clarity the Examiner suggests deleting the right parathesis immediately after the recitation “acids” as discussed above.
Claim 16, line 2, the Examiner respectfully notes there is a missing period immediately after the recitation “glyceride”. Thus, to promote clarity the Examiner suggests inserting a period immediately after the word “glyceride” as discussed above.
Appropriate correction is required.
Claim Interpretation
Claim 10, lines 7-8, recite the phrase “wherein said formulation exhibits enhanced bioavailability upon oral administration”. The Examiner respectfully notes that claim 10 is a product claim and therefore reasonably interprets that the recited limitation above is an intended effect of the product.
Additionally, claim 10 recites said formulation contains ivermectin, an oily solvent, a surfactant, a co-surfactant, and an antioxidant within the formulation at the recited weight percentages within lines 3-7 of the claim.
Therefore, the Examiner reasonably interprets that the body of the claim fully and intrinsically sets forth all of the limitations of the claimed invention, and thus the statement “wherein said formulation exhibits enhanced bioavailability upon oral administration” is reasonably interpreted by the Examiner to be an intended effect of the claimed formulation.
Furthermore, the Examiner does not find anything in the Specification where the recited phrase above provides any distinct definition of any of the claimed invention’s limitations, and thus the phrase “wherein said formulation exhibits enhanced bioavailability upon oral administration” is reasonably interpreted by the Examiner to be an intended effect of the recited structural limitations of claim 10 as discussed above.
Therefore, in view of the foregoing reasons discussed above, the Examiner does not consider the recited phrase of “wherein said formulation exhibits enhanced bioavailability upon oral administration” to be a limitation of the claim and thus the recited limitation above is not provided patentable weight and is of no significance to claim construction.
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 10-29 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.
Claim 10 and Claim 21 are drawn to a formulation of ivermectin for incorporation into softgel capsules, with respect to claim 10; or within a softgel capsule with respect to claim 21.
Additionally, claim 10 and claim 21 both recite the terms “oily solvent”, “surfactant” or “co-surfactant” as components within the formulation as recited in claim 10 or claim 21.
Moreover, claims 24 and 29 recite the term “plasticizer” as a component with the gelatin of the soft-gel capsule recited in claim 21.
Although, the Examiner respectfully notes the Specification does not explicitly define the terms “oily solvent”, “surfactant”, “co-surfactant” or “plasticizer”. The Specification exemplifies the following:
(a) when referring to the “oily solvent”, the Specification exemplifies the oily phase comprises about 95% medium chain triglycerides, see pg. 8, line 15; medium chain triglycerides containing 8 to 12 carbon atoms, see pg. 9, lines 15-16; as well as the examples listed on pg. 10, lines 3-6;
(b) when referring to the “surfactant”, the Specification exemplifies the term includes linoleoyl polyoxyl-6 glycerides, see pg. 9, line 17; as well as the examples listed on pg. 10, lines 7-10;
(c) when referring to the “co-surfactant”, the Specification exemplifies the term includes propylene glycol monocaprylate, see pg. 9, line 18; as well as the examples listed on pg. 10, lines 11-15; and
(d) when referring to the “plasticizer”, the Specification exemplifies the term includes glycerin, sorbitol, sorbitan and propylene glycol, see pg. 10, the last two lines of the page.
However, the Examiner respectfully notes that exemplification is not an explicit definition.
Furthermore, the Examiner respectfully notes explicit definitions for “oily solvent”, “surfactant”, “co-surfactant” or “plasticizer” are of particular relevance and importance as:
(i) the Specification states it is of paramount importance for formulation scientists to explore the potential of a self-emulsifying delivery system by combining appropriate excipients based on critical parameters which allow it to be administered for oral administration, see pg. 7, lines 2-5;
(ii) the Specification states only some preferred embodiments have been illustrated by way of example, and that it is appreciated that the formulation of ivermectin in soft capsules, as well as the configurative arrangements can be chosen from a plurality of alternatives without departing from the spirt of the invention, see pg. 13, lines 4-7; and
(iii) the Examiner respectfully notes that both claim 10 and claim 21 contain identical percentages by weight of “oily solvent”, “surfactant” and “co-surfactant” within their formulations, respectively; and where the Examiner respectfully notes that claim 10 also states “said formulation exhibits enhanced bioavailability upon oral administration, see claim 10, lines 7-8.
Thus, the terms “oily solvent”, “surfactant”, “co-surfactant” and “plasticizer” are all unclear and indefinite as to the scope of these terms and thus the metes and bonds of each of these terms are unclear and indefinite as to what other structures are to be included in the terms “oily solvent”, “surfactant”, “co-surfactant” and “plasticizer” other than the structures exemplified within the Specification, and particularly, the Examiner also respectfully notes that it’s unclear and indefinite as to what structures are to be excluded from each of these terms within these formulations in view of claim 10 reciting said formulation exhibits enhanced bioavailability upon oral administration as discussed above.
Claims 11-20 are included in this rejection as they depend from the formulation of claim 10.
Claims 22-29 are included in this rejection as they depend from the formulation of claim 21.
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.
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.
(I) Claims 10-26 are rejected under 35 U.S.C. 103 as being unpatentable over Dugger (Published 30 June 2005, US-20050142069-A1, PTO-892) in view of Cleverly et al. (Published 09 July 2015, US-20150190417-A1, PTO-892) and Soll et al. (Published 07 October 2004, US-20040198676-A1, PTO-892).
Regarding claims 10-26, Dugger teaches capsules containing drugs for treating an infectious disease, see title; wherein the soft-bite gelatin capsule using a non-polar solvent provides biologically active compounds for rapid absorption through the oral mucosa, resulting in the fast onset of effect, see paragraph [0003]; because the enhanced absorption of the compound through the oral mucosa and no chance of a first pass effect, will eliminate much of the lag time of typical capsules which are swallowed whole or bitten and then swallowed, resulting in hasten onset of biological effect, see paragraph [0020], (e.g. exhibits enhanced bioavailability upon oral administration, required in claim 10, lines 7-8).
Dugger teaches a soft-bite gelatin capsule (e.g. the softgel capsule, required in claims 10 and 21-23), see paragraph [0003].
Dugger teaches the shell of the soft gelatin capsule may comprise gelatin from 50-75%, glycerin from 20-30% and sorbitol from 2-10% (e.g. the capsule, required in claims 24-26), see paragraph [0020].
Dugger teaches soft-bite gelatin capsules for transmucosal administration of a pharmacologically active compound, see paragraph [0008], wherein transmucosal administration includes systemic circulation, see paragraph [0024] and Fig. 1; and wherein the capsule comprises in weight % of the total composition of the following ingredients, see paragraph [0008];
(i) active compound between 0.01-80%, see paragraph [0008], wherein the active compound is an anti-parasitic agent, wherein suitable anti-parasitic agents include ivermectin (e.g. the ivermectin, required in claim 10, line 3 and claim 21, line 3), see paragraph [0039];
(ii) non-polar solvent between 4-99.99%, see paragraph [0008], wherein suitable non-polar solvents for the capsules include corn oil, soya oil and other vegetable oils (e.g. the vegetable oils, required in claim 11) and C2-C24 fatty acid C2-C6 esters and the triglycerides of the corresponding acids, see paragraph [0027]; and is preferably a C7-18 hydrocarbon of a linear or branched configuration, fatty acid esters, and triglycerides, such as Miglyol (e.g. the medium chain triglycerides, required in claim 11), see paragraph [0015];
and
(iii) emulsifier between 0-20%, see paragraph [0008].
The Examiner respectfully notes the teachings discussed in (ii) of Dugger above correspond to the limitation of 60-80% by weight of an oily solvent, required in claim 10, line 4 and claim 21, line 4.
Although, Dugger does not teach (a) caprylic/capric triglyceride, required in claim 12; (b) polyoxyl-6 linoleoyl glyceride, required in claims 13, 16 and 21; (c) propylene glycol monocaprylate, required in claims 14, 17 and 21; (d) propylene glycol dicaprylate/dicaprate, required in claims 14, 18 and 21; (e) butylhydroxyanisole, required in claims 15, 19 and 21; and (f) DL-α-tocopherol, required in claims 15, 20 and 21.
However, in the same field of endeavor of formulations with ivermectin as the pharmaceutically active agent, with respect to limitations (a), (c), (e) and (f), Cleverly teaches a chewable formulation for delivering a pharmaceutically active agent, see abstract; wherein said agent is an anthelmintic such as a macrocyclic lactone, for example the macrocyclic lactone could be selected from and including ivermectin, see paragraph [0310].
Cleverly teaches the pharmaceutically active agent is combined with one or more ingredients selected from, see paragraph [0172];
(iv) an antioxidant, see paragraph [0179], wherein within the chewable formulation comprises about 0.1, 0.2, 0.3, 0.4, 0.5 or 1% by weight of an antioxidant, and useful ranges may be selected between any of these values, see paragraph [0139]; wherein example antioxidants include ascorbyl palmitate (e.g. required in claim 15), BHA (e.g. butylhydroxyanisole, required in claim 15 and claim 19) or α-tocopherol (e.g. required in claim 15 and claim 20), see paragraph [0350] and Table 1; and wherein the chewable formulation comprises the antioxidant to protect the active ingredient from oxidation (e.g. the ivermectin taught by Cleverly above), see paragraph [0414];
the Examiner notes the teachings of (iv) of Cleverly above correspond to the antioxidant required in the formulation recited in claim 10, line 7 and claim 21, line 7;
(v) a solubility enhancer, see paragraph [0187], wherein the solubility enhancer is selected from and including caprylic/capric glycerides (e.g. the caprylic/capric triglyceride, required in claim 12);
the Examiner notes the teaching of (v) of Cleverly above combined with the teachings of (ii) wherein the non-polar solvent is between 4-99.99% by weight of the soft gelatin capsule of Dugger as discussed above corresponds to the oily solvent required in claim 10, line 4, claim 12 and claim 21, line 4; and
(vi) a surfactant, see paragraph [0186]; wherein the formulation comprises about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19% and 20% surfactant by weight, see paragraph [0152]; where the surfactant is selected from and including propylene glycol monocaprylate (e.g. the co-surfactant, required in claims 14 and 17), see paragraph [0153]; wherein surfactants are solubility enhancers, see paragraph [0156];
and wherein Cleverly teaches solubility enhancers enhance the solubility of the pharmaceutically active agent (e.g. the ivermectin taught by Cleverly above), see paragraph [0154].
With respect to limitations (b) and (d), Soll teaches antiparasitic formulations are known in the art and include oral formulations, see paragraph [0009], wherein a pharmaceutical combination consisting of a macrocyclic lactone such as ivermectin, see paragraph [0077]. Soll teaches a solvent pair, i.e. a mixture of two solvents one of which dissolves the macrocyclic lactone and the second of which dissolves the anthelmintic agent used to form the solutions, where solvents that may be used in solvent pairs preferably include MiglyolR 840 (propylene glycol dicaprylate/dicaprate) (e.g. propylene glycol dicaprylate/dicaprate, required in claims 14 and 18) and alcoholysis/esterification product of apricot kernel oil and PEG 300 (LabrafilR M 1944 CS) (e.g. linoleoyl polyoxyl-6 glyceride, required in claims 13 and 18, as evidenced by the Specification on pg. 10, lines 9-10), see paragraph [0063].
The Examiner respectfully notes the teachings of Soll discussed above combined with the teachings of (vi) wherein the surfactant can be about 10-20% by weight of the formulation as taught by Cleverly above correspond to the surfactant of claim 10, line 5, claim 13, claim 16 and claim 21, line 5; and correspond to the co-surfactant of claim 10, line 6, claim 14, claim 18 and claim 21, line 6.
Additionally, the Examiner respectfully notes that one of ordinary skill in the art would have been motivated to incorporate propylene glycol dicaprylate/dicaprate as taught by Soll above into the formulation as taught by Dugger above, as Dugger teaches Miglyol can be used as a non-polar solvent as discussed above; and as evidenced by the Specification which discloses propylene glycol dicaprylate/dicaprate as MiglyolTM 810 on pg. 10, line 5.
Moreover, the Examiner respectfully notes that one of ordinary skill in the art would have been motivated to incorporate the alcoholysis/esterification product of apricot kernel oil and PEG 300 (LabrafilR M1944 CS) as taught by Soll above into the formulation as taught by Dugger above as Soll teaches LabrafilR M 1944 CS is a solvent of ivermectin which is the active pharmaceutical agent of Dugger; and wherein Dugger teaches the formulation can include an emulsifier as discussed above, which as evidenced by the Specification discloses LabrafilR M 1944 CS as a solubilizing and emulsifying agent on pg. 10, lines 9-10.
Furthermore, the Examiner respectfully notes the teaching of Soll discussed above combined with the teachings of (vi) wherein the surfactant can be about 10-20% by weight of the formulation as taught by Cleverly above and/or with the teachings of (iii) wherein the emulsifier is between 0-20% by weight of the soft gelatin capsule of Dugger as discussed above corresponds to the surfactant or co-surfactant required in claim 10, lines 5-6, claims 13-14, claim 16, claim 18, and claim 21, lines 5-6.
With respect to the limitation “said gelatin is of animal or vegetable origin”, required in claim 23; the Examiner reasonably interprets this limitation to be a physical limitation of said gelatin. Since Dugger teaches a soft-bite gelatin capsule as discussed above the physical limitation relating to the origin of the gelatin will be met.
It would have been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have incorporated limitations (a)-(f) into the composition as taught by Dugger above as within the scope of the artisan as combining prior art elements according to known compositions to yield predictable results.
One of ordinary skill in the art would have been motivated to incorporate limitation (a) and (c) to enhance the solubility of the pharmaceutically active agent, specifically ivermectin as taught by Cleverly above; limitations (e) and (f) to protect the active ingredient from oxidation (e.g. the ivermectin taught by Cleverly above); and limitations (b) and (d) as a solvent pair to dissolve and emulsify the macrocyclic lactone such as ivermectin as taught by Soll above, which the Examiner notes are all particularly advantageous when applied to a soft gelatin capsule containing a pharmaceutically active agent such as ivermectin within a non-polar solvent for transmucosal administration as taught by Dugger above. One of ordinary skill in the art would have had a reasonable expectation of success to have included limitations (a)-(f) into the soft gelatin capsules as taught by Dugger above, as both Cleverly and Soll are drawn to compositions that teach incorporating limitations (a)-(f) into compositions that contain ivermectin as the pharmaceutically active agent as discussed above.
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included limitations (a)-(f) into the soft gelatin capsule as taught by Dugger above as within the scope of the artisan as combining prior art elements according to known compositions to yield predictable results. One of ordinary skill in the art would have been motivated to incorporate limitations (a)-(f) into the soft gelatin capsule of Dugger in order to create a soft-bite gelatin capsule using a non-polar solvent to provide biologically active compounds for rapid absorption through the oral mucosa as taught by Dugger above. One of ordinary skill in the art would have had a reasonable expectation of success to have incorporated limitations (a)-(f) into the soft gelatin capsules as taught by Dugger above, as Dugger, Cleverly and Soll are all drawn to compositions comprising ivermectin as the pharmaceutically active agent as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(II) Claims 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Dugger (Published 30 June 2005, US-20050142069-A1, PTO-892), Cleverly et al. (Published 09 July 2015, US-20150190417-A1, PTO-892) and Soll et al. (Published 07 October 2004, US-20040198676-A1, PTO-892) as applied to claims 10-26 above, and further in view of Zhao et al. (Published 29 September 2016, US-20160279056-A1, PTO-892).
Dugger, Cleverly and Soll address claims 10-26 as written above. Although, Dugger, Cleverly and Soll do not teach wherein the gelatin further includes collagen, required in claims 27-29.
However, in the same field of endeavor of soft gelatin capsules with followable fill compositions, Zhao teaches oral pharmaceutical compositions suitable for chewing, sucking, or buccal dissolution comprising soft gel capsules and liquid fills, methods of making the same, and methods of treating subjects in need thereof with such capsules, see paragraph [0003]; and wherein the flowable fill comprises one or more active pharmaceutical ingredients or nutraceuticals, see paragraph [0008].
Zhao exemplifies a soft gel capsule, wherein the capsule shell formulation contains polymers exemplified as gelatin at a weight percent of 67% and hydrolyzed collagen from 0-7% (e.g. the percentage of collagen, required in claim 28) and wherein exemplified plasticizers include glycerol between 10-50% (e.g. the glycerin taught by Dugger above) to encapsulate the matrix fill liquid formulation in Table 2, see pg. 11, paragraph [0094] and Table 2.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have incorporated collagen at up to 7% by weight of the shell of the soft gelatin capsule as taught by Dugger above as within the scope of the artisan as combining prior art elements according to known compositions and methods to yield predictable results. One of ordinary skill in the art would have been motivated to include the collagen in order to create the shell of the soft gel capsule which comprises between gelatin from 50-75% and glycerin from 20-30% to provide biologically active compounds for rapid absorption through the oral mucosa as taught by Dugger above. One of ordinary skill in the art would have had a reasonable expectation of success to have included collagen at up to 7% by weight, as Zhao teaches softgel capsules wherein the shell contains gelatin at a weight percent of 67% and glycerol at a weight percent between 10-50%, which the Examiner respectfully notes are both within the range of the shell of the soft gelatin capsule as taught by Dugger above, and wherein both Dugger and Zhao teach soft gelatin capsules encapsulating liquid fills comprising pharmaceutically active agents; and wherein Zhao teaches a method of making the soft gel capsules as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARET J CREWS whose telephone number is (571)270-0962. The examiner can normally be reached Monday-Friday: 9:00am-5:30pm EST.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691