Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Request for Continued Examination
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/17/2025 has been entered.
DETAILED ACTION
Claims 1, 18, 22 and 27, 29, 31, 34, 35, 36 and 41 are pending in the Claim Set filed 12/17/2025.
Claims 1, 29 and 34 have been amended.
Claims 2-17, 19-21, 23-26, 28, 30, 32, 33 and 37-40 are canceled.
Claims 18 and 22 remain withdrawn.
Applicants elected species is as follows: Oleic acid (lipophilic surfactant); polyoxyethylene (40) hydrogenated castor oil (hydrophilic surfactant); A Maximum testosterone concentration that does not concentration exceed 1500 ng/dL when administered with a meal. (Maximum testosterone concentration).
Herein, claims 1, 27, 29, 31, 34-36 and 41 are for examination to the extent that they read on the elected species.
Withdrawn Rejection
The rejection of claims 39 and 40 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Vies (USP 4147783, cited in IDS) [Vies] in view of Lacy et al (WO 95/24893, Foreign Patents Documents, Cite No. 180, cited in IDS) [Lacy] and Giliyar et al (US 20100173882, cited in IDS) [Giliyar] as applied to claims 1, 6, 8, 27, 28, 29, 31-38 and 41 above and further in view of Liao et al (USP 5605929, Cite No. 9, cited in IDS filed 8/22/2023) [liao] and Wacher et al (Peppermint Oil; Journal of Pharmaceutical Sciences, Cite No. 412, cited in IDS filed 8/22/2023) [Wacker] is withdrawn because claims 39 and 40 are canceled in in the Instant Claim Set filed 12/17/2025.
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 27 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 pre-AIA the applicant regards as the invention.
Regarding Claim 27:
Base claim 1 is directed to a capsule comprising a pharmaceutical composition a pharmaceutical composition and not a method. Thus, claim 1 does not require administration in a subject and it is unclear what is contemplated by claim 27, which is directed to a limitation associated with administration in a subject, which is not required by claim 1. Thus, it is unclear whether claim 27 is intended to be a limitation of the amount of testosterone undecanoate in each capsule, which already requires 18 to 22 %wt. of solubilized testosterone undecanoate (claim 1), or whether claim 27 is a limitation on the functional limitation of claim 1 associated with the intended use of the capsule, i.e., ‘upon twice-daily administration with a meal to a male subject’, or if claim 27 was intended to depend from withdrawn method claim 18. As written, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 103
(Reformulated and made again)
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 27, 29, 31, 34-36 and 41 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Vies (USP 4147783, cited in IDS) [Vies] in view of Lacy et al (WO 95/24893, Foreign Patents Documents, Cite No. 180, cited in IDS) [Lacy] and Giliyar et al (US 20100173882, cited in IDS) [Giliyar]. Rejections set forth below have been reformulated in view of the claim amendments.
CLAIM INTERPRETATION
The transitional term ‘comprising’ is open-ended and does not exclude additional, unrecited elements or method steps. See, e.g. Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). Further, the claims are directed to a capsule comprising a pharmaceutical composition, thus, the recitations of intended use with respect to administering the capsule to a subject, i.e., twice daily oral administration with a meal to a male subject (claim 1), and the amount administered per day (claim 27) are given no patentable weight. MPEP 2111.02.
Regarding claims 1, 27, 29, 31, 34-36 and 41,
Vies teaches an oral pharmaceutical composition comprising a capsule and a liquid pharmaceutical preparation within the capsule, wherein the liquid comprises one or more esters of testosterone, e.g., testosterone undecanoate, in combination with a lipoid (Abstract; col.1, lns.1-60; col,3, lns.50-67; col.5, lns.48-66; col.6, lns.3-25; col.7, lns.57-69 to col.8, lns.1-3; Vies: claim 7; See entire document). Vies teaches that the lipoid substance is preferably oleic acid (i.e., lipophilic surfactant: elected species) (col. 3, lns.25-30). Vies teaches that the oral pharmaceutical preparation comprises 1-40% testosterone undecanoate by weight in the composition (Abstract; col.5, lns.48-66; col.6, lns.21-25; See entire document) and that the lipoid substance, e.g., oleic acid, constitutes about 25% to about 95% by weight of the preparation (Vies: claims 1-5). Vies teaches orally administering daily to a subject 400 mg of testosterone undecanoate, together with a lipoid substance, e.g., preferably, oleic acid (col.7, lns.40-70; claim 7). Vies teaches that testosterone undecanoate is dissolved in the lipoid substance, e.g., oleic acid, and the solution is processed to provide a liquid pharmaceutical dosage form that is administered orally in the form of a capsule (col,3, lns.1-25; col.5, lns.5-39). Thus, the teachings of Vies makes obvious to one of ordinary skill in the art at the time of the invention to provide solubilized testosterone undecanoate (TU), for example, a liquid solution comprising testosterone undecanoate and oleic acid that is encased in a capsule. Moreover, Vies teaches oleic acid provides for high dissolving power and enhances solubility of testosterone undecanoate [emphasis added] [emphasis added] (col.3, lns.39-42). The amount of testosterone undecanoate of 1-40 % by weight encompasses the claimed amount. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257,191 USPQ 90 (CCPA 1976); In re Woodruff, 91 9 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05.
Accordingly, a person of ordinary skill in the art would have recognized that oleic acid effectively dissolves testosterone esters. Consequently, they would have been motivated to use oleic acid in a testosterone undecanoate capsule composition to enhance its solubility. Therefore, the teachings of Vies establishes oleic acid’s strong dissolving power for testosterone undecanoate providing both motivation and a reasonable expectation of success.
However, Vies does not teach that the oral pharmaceutical composition comprising a capsule and a liquid pharmaceutical preparation within the capsule, of which further comprises a hydrophilic surfactant that is polyethylene (40) hydrogenated castor oil (also known as Cremophor RH40), therefore, it lacks the hydrophilic surfactant required by the claims.
However, Lacy cures the deficiencies.
Lacy teaches oral drug delivery systems for hydrophobic drugs for improving the bioavailability of hydrophobic drugs from such systems comprising a carrier system for a wide range of different hydrophobic drugs (p.1, lns.1-4; p.5, lns.15-26). Lacy teaches administration of a hydrophobic drug in an oil-based oral delivery systems comprising a digestible oil and further comprises a hydrophilic surfactant and lipophilic surfactant (p.6 to p.7). Lacy teaches the hydrophilic surfactant component may inhibit the lipolysis of a digestible oil so that a lipophilic surfactant capable of reducing the inhibitory effect of the hydrophilic surfactant component is employed, wherein the pharmaceutical composition improves the in vivo bioavailability of the hydrophobic drug (p.5, lns.15-28; p.7-p.8; claims 1-19; See entire document). Lacy teaches that the lipophilic surfactant(s) is/are a fatty acid such as oleic acid (preferred: elected species; recited in Instant Claim 1) and linolenic acid (recited in Instant Claim 29 (p.9, lns.1-10; p.12, lns.10-13; See entire document). Further, Lacy teaches that the hydrophilic surfactant is preferably Cremophor RH40 (also known as polyoxyethylene (40) hydrogenated castor oil: elected species) (p.14, lns.16-18; p.15, line 15). Lacy teaches that the digestible oil serves not only the function of providing a base carrier (i.e., reads on carrier in Instant Claims) for the hydrophobic drug, but also serves as an in vivo source of lipolytic products whereby the in vivo absorption of the hydrophobic drug is enhanced (p.17, lns.13-29). Lacy teaches that the digestible oil includes soyabean oil, safflower seed oil, cottonseed oil and coconut oil (See examples, p.18; all of these vegetable oils are disclosed in Specification at [0095]). Lacy teaches that the carrier system comprises: 0.1% to 50% by weight of a hydrophobic drug and correspondingly from 50% to 99.9% by weight of said carrier system; 10-90% by weight of digestible oil; 10-60% by weight of a hydrophilic surfactant component, e.g., Cremophor RH40; and 5-60% by weight of a lipophilic surfactant component, e.g., oleic acid (Lacy: claims 7, 12, 13; p.25, lns.25-29). The amount of hydrophobic drug, hydrophilic surfactant and lipophilic surfactant encompasses the claimed amounts. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257,191 USPQ 90 (CCPA 1976); In re Woodruff, 91 9 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05. moreover, Lacy teaches that the hydrophobic drug includes sex hormones (p.25, lns.13-17). Further, Lacy teaches that the pharmaceutical compositions for oral administration are preferably liquids, wherein preferred compositions are liquid oral unit dosage forms (p.2, lns.10-12; p.28, lns.27-35; claims 15, 16). Moreover, the normal desire of scientists or artisans to improve upon what is already generally known would provide the motivation to determine the optimum weight percent amounts of each component to optimize the in vivo bioavailability of the hydrophobic drug. Optimization of parameters is a routine practice that would be obvious to a person of ordinary skill in the art to employ and reasonably expect success. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955) & MPEP 2144.05.
Accordingly, the teachings of Lacy renders obvious providing a pharmaceutical composition comprising a hydrophilic surfactant, e.g., Cremophor RH40 (also known as polyoxyethylene (40) hydrogenated castor) and the lipophilic surfactant. e.g., oleic acid, in combination having a reasonable expectation to enhance the solubilization of testosterone undecanoate and improve its in vivo bioavailability. Furthermore, Lacy teaches that the drug formulation comprising the digestible oil (i.e., carrier) when in the stomach is physically emulsified with the gastric juice to form an oil-in-water emulsion, wherein hydrophobic drugs will reside predominantly within the dispersed (i.e., oil) phase of this emulsion as either a solution or partial suspension (p.26, lns.10-33). Thus, Lacy renders obvious a self-emulsifying drug delivery formulation. Additionally, Lacy teaches that the pharmaceutical preparations are provided by mixing the digestible oil with a lipophilic surfactant effected by the use of a homogenizing mixer; then the hydrophilic surfactant is added; next, the hydrophobic drug is added to the combined liquids and mixing is combined to provide a homogeneous solution (p.29, lns.1-22), i.e., complete solubilization of testosterone undecanoate.
Thus, it would have been obvious to one of ordinary skill in the art at the time of the invention to modify the preparation as taught by Vies to further comprise a digestible oil and a hydrophilic surfactant, to provide a pharmaceutical composition comprising solubilized testosterone undecanoate (hydrophobic drug: also, taught by Vies), oleic acid (lipophilic surfactant: also taught by Vies), Cremophor RH40 (also known as polyoxyethylene (40) hydrogenated castor oil: preferred hydrophilic surfactant as taught by Lacy) and a digestible oil (carrier, as taught by Lacy). Moreover, one of ordinary skill in the art would have been motivated to modify Vies in order to improve the in vivo bioavailability of testosterone undecanoate because the lipolysis of a digestible oil within the gastrointestinal tract would naturally enhance the dissolution rate of a testosterone undecanoate, wherein Cremophor RH40 would be expected to provide an oil-water emulsion that uniformly empties from the stomach and further promote faster and more complete absorption of testosterone undecanoate, wherein oleic acid would ensure good homogeneity of testosterone undecanoate (i.e., Also, See Vies) and substantially inhibit the hydrophilic surfactant from inferring with the lipolysis of the digestible oil as expressly taught by Lacy (p.1, lns.24-32 to p.2, lns.1-9; pgs.6-9; See entire document).
However, Vies and Lacy do not teach a total lipophilic surfactant-to-total hydrophilic surfactant ratio (w/w) of about 6:1 to 3.5:1 to provide an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range (300-1100 ng/dL: See Specification at para. [0009]) or where the maximum testosterone concentration of (Cmax) does not exceed 1500 ng/dL, upon twice-daily oral administration with a meal to a male subject,
Giliyar cures the deficiencies.
Giliyar teaches an oral dosage form comprising testosterone undecanoate ([0006]; [0009]; [0033-0035]), at least one hydrophilic surfactant (e.g., Cremophore RH 40 (Table 5, page 22; i.e., polyoxyethylene (40) hydrogenated castor oil) and at least one lipophilic surfactant ([0033]; [0037]; [0047] (e.g., oleic acid [0069]; p.23, [0098], left column, Table 8: mixture oleic acid with stearic acid). Giliyar teaches pharmaceutical composition having lipophilic agent solubilizing the testosterone undecanoate [0020-21]. Giliyar teaches testosterone undecanoate 10-20% w/w in a capsule (overlaps with claimed amount) (Table 20 [0136]; [0121]; [0126]; [0128-0130]; See entire document). Giliyar teaches a ratio of lipophilic surfactant (55-70%) to hydrophilic surfactant (10-20%) of which is a ratio of about 7:1 to 2.7:1 (Table N, p.10; Table B ratio 4:1) Table(s) A-I [0050]; See entire document), which would encompass the lipophilic surfactant to hydrophilic surfactant ratio of 6:1 to 3.5:1, as claimed. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP 2144.05. Further, Giliyar teaches administration of an oral dosage form comprising testosterone undecanoate to an individual upon once a day or twice a day ([0036]; [0068]), which composition provides a plasma concentration of testosterone undecanoate at steady state concentration that is between about 200 ng/dL and 1300 ng/dL (i.e., in certain embodiments: 300-1000ng/dL) [0057] (i.e., lies within eugonadal range: 300-1100 ng/dL: See Specification [0009]). Giliyar teaches testosterone undecanoate therapies of pharmaceutical compositions and oral dosage forms provide a plasma Cmax of testosterone that is less than 1500 ng/dL [0054], wherein the individual is an adult hypogonadal adult male human ([0055]). Furthermore, Giliyar teaches provided herein is a pharmaceutical composition or oral dosage form that provides or is formulated to provide a testosterone (e.g., in human males, adult human males, pubescent human males, or the like) mean plasma Cmax at steady state of about 1550 ng/dL or less, about 1500 ng/dL or less, about 1450 ng/dL or less, about 1400 ng/dL or less, about 1310 ng/dL or less, about 1300 ng/dL or less [0062]; Cmax is about 500 ng/dL to about 1500 ng/dL [0080] (reads on claims 1 and 41). Where 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). MPEP 2144.05.
Further, the oral pharmaceutical capsule as taught by the Vies, Lacy and Giliyar, which comprises a capsule composition 10-20 w/w solubilized testosterone, 55-70 wt% oleic acid (elected species: lipophilic surfactant), 10-20 %wt Cremophor (polyoxyethylene (40) hydrogenated castor oil; elected species: hydrophilic surfactant) and a digestible oil, wherein the oleic acid: Cremophor ratio (w/w) is about 7,:1 to 2.7:1, identical to the claimed oral pharmaceutical capsule composition comprising about 18-22 %wt solubilized testosterone undecanoate, about 50-70 %wt oleic acid (lipophilic surfactant, about 15-17 %wt polyoxyethylene (40) hydrogenated castor oil (Cremophor RH 40: hydrophilic surfactant), wherein the oleic acid: polyoxyethylene (40) hydrogenated castor oil ratio is 6:1 to 3.5:1. Thus, where the prior art composition is structurally identical, the oral pharmaceutical capsule composition of Vies, Lacy and Giliyar, (supra) would necessarily be a self-emulsifying drug delivery system (SEEDS) formulation, and would necessarily provide upon twice-daily oral administration in a male subject an average serum testosterone concentration (Cavg) at a steady state in the subject within the eugonadal range, and necessarily provide a maximum testosterone concentration Cmax that does not exceed 1500 ng/dL when administered with a male to a male subject, and necessarily provide a maximum testosterone concentration Cmax is from 900 ng/dL to about 11 nd/dL when administered with a meal to a male subject. As evidenced by the specification (para. [0065], the identical oral pharmaceutical capsule of Vies, Lacy and Giliyar, would necessarily have self-emulsifying properties and be a self-emulsifying drug delivery system (SEEDS). These properties of the claimed capsule composition would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation(s) at issue is the 'natural result' of the combination of prior art elements." PAR Pharm., Inc. v. TWI Pharms., Inc., 773 F.3d 1186, 1195 (Fed. Cir. 2014) (quoting In re Oelrich, 666 F.2d 578,581 (CCPA 1981)).Where the claimed and prior art products are identical or substantially identical in structure or composition, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433.
Therefore, the claimed invention as a whole would have been obvious to one of ordinary skill in view of Vies, Lacy and Giliyar, as a whole.
Response to Arguments
Applicants argue:
The Instant Claims Are Commensurate in Scope with the Unexpected Results
The Advisory Action asserts that "the unexpected results are not commensurate in scope with what is instantly claimed, because the scope of Instant Claims encompasses, at least, one or more lipophilic surfactant(s) described in Applicants' Specification in para. [0037-0045] and mixture thereof [0046]. The Advisory Action also notes that the formulation in the Dudley Declaration is a SEDDS formulation and that it "is unclear whether claimed invention claimed invention is a SEDDS formulation and whether the data presented in Table 1 is applicable to instantly claimed invention." Applicant argue in order to advance prosecution, the pending claims have been amended to recite that the carrier comprises "a lipophilic surfactant comprising oleic acid in an amount of from about 50 to about 70 percent by weight based on the total weight of the composition" and "a hydrophilic surfactant comprising polyoxyethylene (40) hydrogenated castor oil in an amount of from about 15 to about 17 percent by weight based on the total weight of the composition," and to recite "wherein the oral pharmaceutical composition is a self-emulsifying drug delivery system (SEDDS) composition." The pending claims thus require each of the key elements of the composition that together produce the superior results detailed in the instant application and in the Dudley Declaration: the presence of oleic acid and polyoxyethylene (40) hydrogenated castor oil as lipophilic and hydrophilic surfactants, each present in a specific amount, wherein the amount of total lipophilic surfactant and total hydrophilic surfactant is such that their ratio is "in the range of 6:1 to 3.5: 1," and wherein the composition is a SEDDS formulation. Claim 34 further requires that the "the oleic acid is present in an amount of from about 50 to about 55 percent by weight of the oral pharmaceutical composition"). Accordingly, the pending claims are commensurate in scope with the claimed invention.
Moreover, the data presented in Table 1 of the Dudley Declaration confirms the surprising superiority of the claimed invention. As detailed in the instant application, "the formulations of the invention are designed to be self-emulsifying drug delivery systems (SEDDS) so that a TU-containing emulsion (or dispersion) is formed upon mixing with intestinal fluids in the gastrointestinal tract." See as filed application at paragraph [0046]. As observed in the Advisory Action at page 10, referring to the as filed specification at page 34, paragraph [0107] (See Applicants argument at page 7, first full paragraph).
Statistical comparisons of the serum T response observed after oral TU was taken without food or with a very low fat, low fat, or high fat diet versus a normal fat diet (i.e., reference diet) revealed that there was no statistically significant difference at the p<0.05 level between the low-fat or high-fat diets versus the normal diet. Conversely, administration of oral TU as a SEDDS formulation while fasting or with a very low-fat breakfast yielded serum T PK parameters significantly different (i.e., lower) from a normal diet. Accordingly, the fat content of meals taken with the inventive formulations can differ substantially from 'normal', without a clinically significant impact on the levels of T obtained. Thus, a patient is permitted flexibility in eating habits from meal to meal, and from day to day, which could not have been heretofore possible with known oral TU formulations. Oral TU formulations known in the art have heretofore been unable to achieve any meaningful serum T levels in the fasted state.
Thus, while the drug is to be taken with a meal, the instantly claimed oral TU formulation allows flexibility as to whether that meal is a low, normal, or high fat diet. In other words, the patient no longer has to be concerned about varying fat content in their diet. This is yet another surprising benefit of the claimed formulation.
The Advisory Action acknowledges that the element of an oral TU as a SEDDS formulation affords pharmacokinetic parameters that are "significantly different" from those possible with alternative oral TU formulations, regardless of the fat content of the meal, and further acknowledges that these differences afford a meaningful improvement in patient quality of life. Thus, the Advisory Action acknowledges that the element of an oral TU as a SEDDS formulation renders the claimed composition surprisingly superior compared to alternative oral TU formulations. As detailed herein, the pending claims have been amended to expressly recite that the oral TU composition is a SEDDS formulation. Accordingly, the instant claims are commensurate in scope with the surprisingly superior results.
Applicant’s arguments have been fully considered but they are not persuasive, because the claimed composition and the prior art composition of Vies, Lacy and Giliyar, as a whole, are structurally indistinguishable, they would necessarily share identical functional properties. Thus, the prior art of Vies, Lacy and Giliyar, as a whole, has the same self-emulsifying properties and is necessarily a self-emulsifying drug delivery system (SEDDS) formulation. Furthermore, the mere addition of the phrase ‘wherein the oral pharmaceutical composition is a self-emulsifying drug delivery system (SEDDS) formulation’ to instant claim 1 adds no further structurally distinguishing features to the claimed pharmaceutical composition, but merely characterizes a property of what is already claimed and prima facie obvious according to Vies, Lacy and Giliyar, supra. Also, the limitations recited in claim 1: ‘provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, and, ‘wherein the composition provides a maximum testosterone concentration Cmax that does not exceed 1500 ng/dL when administered with a meal, are physical properties of the claimed composition. Because the pharmaceutical composition as taught by the Vies, Lacy and Giliyar, as a whole, where the claimed composition and the prior art composition are structurally indistinguishable, they would share identical functional properties. These properties of the claimed composition would be the natural result of the combination of the prior art elements. Consequently, the composition of the prior art would allow flexibility as to whether that meal is a low, normal, or high fat diet. In other words, the patient no longer has to be concerned about varying fat content in their diet, while the testosterone undecanoate is to be taken with a meal. Furthermore, these properties would not be unexpected in view of the prior art of Vies, Lacy and Giliyar, as a whole. For instance, Vies teaches oleic acid is the preferred lipophilic surfactant because it enhances solubilization of testosterone undecanoate and to dissolve testosterone undecanoate. Lacy renders obvious providing a pharmaceutical composition comprising Cremophor RH40 (also known as polyoxyethylene (40) hydrogenated castor) and oleic acid to enhance the solubilization of testosterone undecanoate and, moreover, improve the in vivo bioavailability of a hydrophobic drug, e.g., testosterone undecanoate. Giliyar teaches an oral dosage form comprising testosterone undecanoate, at least one hydrophilic surfactant, e.g., Cremophore RH 40 (Table 5, page 22; i.e., polyoxyethylene (40) hydrogenated castor oil) and at least one lipophilic surfactant, oleic acid. Furthermore, Giliyar t teaches testosterone undecanoate 10-20% w/w in a capsule (overlaps with claimed amount) and a ratio of lipophilic surfactant (55-70%) to hydrophilic surfactant (10-20%) of which is a ratio of about 7:1 to 2.7:1, which would encompass the lipophilic surfactant to hydrophilic surfactant ratio of 6:1 to 3.5:1, as claimed. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. Consequently, Applicants arguments that the claimed composition provides surprising results is not persuasive, because the results that Applicants are directed to would actually be expected in view of the teachings of Vies, Lacy and Giliyar, as a whole. As is the case here, the obviousness of the claimed invention outweighs any unexpected results argued by Applicants.
Regarding whether Instant Claims are commensurate in scope with the surprisingly superior results. The Exemplary composition TU-4 in the Dudley Declaration contains 51.6 wt% oleic acid ("a lipophilic surfactant") and 16.1 wt% Cremophor RH 40 ("a hydrophilic surfactant") and further contains a ratio total lipophilic surfactant to total hydrophilic surfactant (inclusive of all lipophilic and hydrophilic excipients) of 3.98. See Dudley Declaration at Table 1 (page 5), As shown in Table 1 (See page 9 of Applicants reply filed 8/08/2025), exemplary composition TU-4 includes three lipophilic surfactants (i.e., oleic acid, borage oil, and peppermint oil; see gray shading). Specification at paragraph [0019]: Borage oil and peppermint oil are both considered lipophilic surfactants. The ratio of the total lipophilic surfactant to the total hydrophilic surfactant is, thus, 3.98.
Table 1of the Dudley Declaration contains shown below:
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338
297
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However, the Office would like to point out that instant claim 1 recites (in part): a carrier comprising: (i) a lipophilic surfactant comprising oleic acid; a hydrophilic surfactant comprising polyoxyethylene (40) hydrogenated castor oil. Thus, it clear from the recitation of the transitional phrase ‘comprising; the lipophilic surfactant does not exclude additional lipophilic surfactants and a hydrophilic surfactant does not exclude additional hydrophilic surfactants.
That the transitional term ‘comprising’ is open-ended and does not exclude additional, unrecited elements or method steps. See, e.g. Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004).
Instant Specification at para. [0075] states: As well, it should be apparent to one of ordinary skill in the art that many, if not all, of the surfactants within a category (e.g., lipophilic, hydrophilic, etc.) may be exchanged with another surfactant from the same category. Thus, while Table 1 lists formulations comprising oleic acid, one of ordinary skill in the art should recognize other lipophilic surfactants (e.g., those listed above) rnay be suitable as well. Similarly, while Table l lists formulations cornprising Cremophor RH40 (HLB = 13), one of ordinary skill in the art. should recognize other hydrophilic surfactants (e.g., those listed above) may be suitable. Borage oil, peppermint oil, BHT, and ascorbyl palmitate may be substituted for chemically similar substances or eliminated. Further, Specification at para. [0020] (in part) states: In addition, to Cremophor RH40, Solutol-TS-15, Tween 80 and TPGS are preferred hydrophilic surfactants; and, in addition to oleic acid, Glycerol monoleate, propylene glycol laurate and Capmul MCM are preferred lipophilic surfactants. Further, Specification at para. [0035-0036] states: Lipophilic surfactants suitable in drug delivery systems of the present invention include, for example, octanoic acid, decanoic acid, undecanoic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid. Oleic acid is preferred (Also, See para. [0037-0046] for a laundry list of varied lipophilic surfactants, some examples shown below).
[0037]: Mono- and/or di-glycerides of fatty acids,
[0038]: Acetic, succinic, lactic, citric and/or tartaric esters of mono- and/or diglycerides of fatty acids,
[0039]: Propylene glycol mono- and/or di-esters of fatty acids,
{0040]: Polyglycerol esters of fatty acids
[0041]: Castor oil ethoxylates of low ethoxylate content (HLB<IO)
Accordingly, one of ordinary skill in the art would recognize that ‘a’ lipophilic surfactant’ as instantly claimed is not limited to the total lipophilic surfactant of oleic acid, borage oil and peppermint oil. As described above, a lipophilic surfactant, in accordance with applicants’ specification, can also include one or more lipophilic surfactant(s) selected from at least para. [0037-0045] and mixture thereof [0046]. Moreover, Instant claims do not specifically claim borage oil and peppermint oil as lipophilic surfactants, so the claims encompass additional lipophilic surfactants other than oleic acid, borage oil and peppermint oil.
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range, not just a species or a group of species, for example, lipophilic surfactant of oleic acid, borage oil and peppermint oil. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). Thus, in the instant case, the unexpected results are not commensurate in scope with what is instantly claimed, because the scope of Instant Claims would encompass, would encompass, at least, one or more lipophilic surfactant(s) and/or hydrophilic surfactant(s) described in Applicants’ Specification in para. [0037-0045] and mixture thereof [0046]. The scope of the showing must be commensurate with the scope of claims to consider evidence probative of unexpected results. Therefore, the probative value of the data is not commensurate in scope with the degree of protection sought by the claim(s).
Applicants argue:
The Instant Claims Are Nonobvious over Vies, Lacy, and Giliyar
Applicants argue the instant claims are commensurate in scope with the unexpected results. Moreover, as stated in the Response filed on December 30, 2024, the superior data obtained using the instantly claimed formulation "are particularly surprising in view of Giliyar, which uses less TU and reports a mean Cmax of Capsule 1 of 1820 ng/dL (18.2 ng/mL) after a single dose and 1700 ng/dL (17.0 ng/mL) at steady state." See Response filed on December 30, 2024 at page 20. As to "the test data for women" of Giliyar, such data is not presented to support the instant claims - such data is in the prior art and used for comparative purposes only. Thus, the Applicant has presented data to demonstrate the superiority of the claimed invention and has pointed to the data of Giliyar to further confirm the surprisingness of this superiority. Applicants argue the Advisory Action alleges that the instant specification at paragraph [0070] distinguishes between men and women such that serum T data for women (as in Giliyar) would not be relevant. In fact, paragraph [0070] of the instant specification is discussing testosterone amounts in normal men and women. In a normal man, serum concentrations of testosterone are much higher than in (pre-menopausal) women. However, in a hypogonadal man, serum concentrations of testosterone are much lower. So, too, in a post-menopausal woman, serum concentrations of testosterone tend to be higher. The result is that serum T levels in hypogonadal men and post-menopausal women are more closely aligned. For this reason, post-menopausal women are commonly used as a surrogate for hypogonadal males. Applicants argue that serum T data for post-menopausal women is relevant for treatment of hypogonadal men.
Applicant’s arguments have been fully considered but they are not persuasive, because Giliyar teaches administration of an oral dosage form comprising testosterone undecanoate to an individual upon once a day or twice a day ([0036]; [0068]), which composition provides a plasma concentration of testosterone undecanoate at steady state concentration that is between about 200 ng/dL and 1300 ng/dL (i.e., in certain embodiments: 300-1000ng/dL) [0057], of which render obvious the physical properties recited in instant claims, as discussed above. Moreover, the Examiner would like to point out that the scope of the showing must be commensurate with the scope of claims to consider evidence probative of unexpected results. However, instant claim 1 recites (in part): a carrier comprising: (i) a lipophilic surfactant comprising oleic acid; a hydrophilic surfactant comprising polyoxyethylene (40) hydrogenated castor oil. Thus, it clear from the recitation of the transitional phrase ‘comprising; the lipophilic surfactant does not exclude additional lipophilic surfactants and a hydrophilic surfactant does not exclude additional hydrophilic surfactants. However, Specification at para. [0075] states: As well, it should be apparent to one of ordinary skill in the art that many, if not all, of the surfactants within a category (e.g., lipophilic, hydrophilic, etc.) may be exchanged with another surfactant from the same category. Thus, while Table 1 lists formulations comprising oleic acid, one of ordinary skill in the art should recognize other lipophilic surfactants (e.g., those listed above) rnay be suitable as well. Similarly, while Table l lists formulations cornprising Cremophor RH40 (HLB = 13), one of ordinary skill in the art. should recognize other hydrophilic surfactants (e.g., those listed above) may be suitable. Borage oil, peppermint oil, BHT, and ascorbyl palmitate may be substituted for chemically similar substances or eliminated. Further, Specification at para. [0020] (in part) states: In addition, to Cremophor RH40, Solutol-TS-15, Tween 80 and TPGS are preferred hydrophilic surfactants; and, in addition to oleic acid, Glycerol monoleate, propylene glycol laurate and Capmul MCM are preferred lipophilic surfactants. Further, Specification at para. [0035-0036] states: Lipophilic surfactants suitable in drug delivery systems of the present invention include, for example, octanoic acid, decanoic acid, undecanoic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid. Oleic acid is preferred (Also, See para. [0037-0046] for a laundry list of varied lipophilic surfactants).
Thus, in the instant case, the unexpected results are not commensurate in scope with what is instantly claimed, because the scope of Instant Claims would encompass, at least, one or more lipophilic surfactant(s) and/or hydrophilic surfactant(s) described in Applicants’ Specification in para. [0037-0045] and mixture thereof [0046]. The scope of the showing must be commensurate with the scope of claims to consider evidence probative of unexpected results. Therefore, the probative value of the data is not commensurate in scope with the degree of protection sought by the claim(s).
That is, the pharmaceutical composition comprising testosterone, oleic acid and polyoxyethylene (40) hydrogenated castor oil (The Exemplary composition TU-4 in the Dudley Declaration) that generated said alleged unexpected results are not commensurate in scope with the pharmaceutical composition which is presently claimed. Applicants must further show that the results over the entire claimed range were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The Nutrasweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991). Accordingly, Applicants arguments regarding post-menopausal women are commonly used as a surrogate for hypogonadal males do not the overcome the fact that the unexpected results are not commensurate in scope with what is instantly claimed. Applicants must further show that the unexpected results over the entire scope of instant claims.
Applicants argue the instantly claimed invention would not have been obvious over Vies in view of Lacy and Giliyar. Vies discloses relatively simple oral formulations composed of a lipoid substance and a testosterone ester, wherein the lipoid solubilizes the C9-C16 esters and thereby increases their oral activity. Vies does not disclose a hydrophilic surfactant or the specific ratio of lipophilic surfactant to hydrophilic surfactant required to achieve the specific pharmacokinetic parameters recited herein. In other words, Vies does not disclose self-emulsifying oral formulations as recited herein. Lacy cannot cure the deficiencies of Vies because Lacy does not teach any formulations or methods of treatment using TU. Rather, Lacy acknowledges that broad teachings cannot be applied to drug carrier systems and notes that a separate drug carrier system must be devised for each drug. Thus, neither Vies nor Lacy provide any guidance as to how one skilled in the art might arrive at the specific SEDDS formulation recited herein, which requires specific ingredients (i.e., TU, oleic acid, and polyoxyethylene (40) hydrogenated castor oil) in specific amounts and specific ratios. Applicants argue Giliyar does describe compositions containing TU and further describes polyoxyethylene (40) hydrogenated castor oil as one of hundreds of potential hydrophilic carriers that can be combined with lipophilic carriers in a ratio ranging from 1:99 to 99:1; however, Giliyar does not describe such combinations with oleic acid. Indeed, the only place the word "oleic acid" appears is in the context of an immediate release dosage form (as in the prior art Andriol composition), wherein 90% or more of the TU is released within 15 minutes of exposure. See Giliyar at paragraph [0069]. The immediate release compositions contrast with the delayed release formulations of the invention, wherein the formulation provides "a mean plasma Cmax of testosterone that is at least 5%, at least 10% or at least 15% lower than the mean plasma Cmax of testosterone that is provided by a single dose of an immediate release oral dosage form having an identical amount of the testosterone alkyl ester." Thus, a person of ordinary skill in the art (POSA) reviewing Vies, Lacy, and Giliyar would not have been motivated to select oleic acid for combination with TU and polyoxyethylene (40) hydrogenated castor oil since Giliyar does not describe oleic acid as suitable for delayed release. Further, the POSA would have understood that Giliyar discloses that delayed release is necessary to produce a reduced mean plasma Cmax to ensure that the Cmax does not exceed, e.g., 1500 ng/dL, when administered with a meal.
Applicant’s arguments have been fully considered but they are not persuasive, because the mere addition of the phrase ‘wherein the oral pharmaceutical composition is a self-emulsifying drug delivery system (SEDDS) formulation’ to instant claim 1 adds no further structurally distinguishing features to the claimed pharmaceutical composition. Furthermore, the limitations recited in claim 1: ‘provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, and, ‘wherein the composition provides a maximum testosterone concentration Cmax that does not exceed 1500 ng/dL when administered with a meal, are physical properties of the claimed composition. Accordingly, the pharmaceutical composition as taught by the Vies, Lacy and Giliyar, as a whole, where the claimed composition and the prior art composition would necessarily share identical functional properties. These properties of the claimed composition would be the natural result of the combination of the prior art elements. Moreover, the composition of the prior art would allow flexibility as to whether that meal is a low, normal, or high fat diet. In other words, the patient no longer has to be concerned about varying fat content in their diet, while the testosterone undecanoate is to be taken with a meal. Furthermore, these properties would not be unexpected in view of the prior art of Vies, Lacy and Giliyar, as a whole.
. Moreover, Vies teaches oleic acid provides for high dissolving power and enhances solubility of testosterone undecanoate (col.3, lns.39-42). The amount of testosterone undecanoate of 1-40 % by weight encompasses the claimed amount. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257,191 USPQ 90 (CCPA 1976); In re Woodruff, 91 9 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05. Furthermore, one of ordinary skill in the art would have been motivated to modify Vies in order to improve the in vivo bioavailability of testosterone undecanoate because the lipolysis of a digestible oil within the gastrointestinal tract would naturally enhance the dissolution rate of a testosterone undecanoate, wherein Cremophor RH40 (hydrophilic surfactant) would be expected to provide an oil-water emulsion that uniformly empties from the stomach and further promote faster and more complete absorption of testosterone undecanoate, wherein oleic acid would ensure good homogeneity of testosterone undecanoate and substantially inhibit the hydrophilic surfactant from inferring with the lipolysis of the digestible oil as expressly taught by Lacy (p.1, lns.24-32 to p.2, lns.1-9; pgs.6-9; See entire document). According to MPEP § 2144, IV. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant (In re Kahn, 78 USPQ2d 1329, 1336, Federal Circuit 2006). Additionally, Giliyar teaches (in part) an oral dosage form comprising testosterone undecanoate, Cremophore RH 40 and oleic acid, wherein testosterone undecanoate 10-20% w/w in a capsule (overlaps with claimed amount), wherein a ratio of lipophilic surfactant (55-70%) to hydrophilic surfactant (10-20%) of which is a ratio of about 7:1 to 2.7:1, which would encompass the lipophilic surfactant to hydrophilic surfactant ratio of 6:1 to 3.5:1, as claimed. Further, Giliyar teaches administration of an oral dosage form comprising testosterone undecanoate to an individual upon once a day or twice a day ([0036]; [0068]), which composition provides a plasma concentration of testosterone undecanoate at steady state concentration that is between about 200 ng/dL and 1300 ng/dL (i.e., in certain embodiments: 300-1000ng/dL) [0057] (i.e., lies within eugonadal range: 300-1100 ng/dL: See Specification [0009]). Giliyar teaches testosterone undecanoate therapies of pharmaceutical compositions and oral dosage forms provide a plasma Cmax of testosterone that is less than 1500 ng/dL [0054], wherein the individual is an adult hypogonadal adult male human. The mere fact that a reference suggests a multitude of possible combinations does not in and of itself make any one of those combinations less obvious, see Merck v. Biocraft, 10 USPQ2d 1843 (Fed Cir 1985). Furthermore, it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands. Merck & Co., Inc. v. BiocrafiLabs, Inc., 874 F.2d 804, 807 (Fed. Cir. 1989); In re Corkill, 771 F.2d 1496, 1500. Moreover, Applicant’s arguments are not persuasive, because the addition of the phrase ‘wherein the oral pharmaceutical composition is a self-emulsifying drug delivery system (SEDDS) formulation’ to instant claim 1 adds no further structurally distinguishing features to the claimed pharmaceutical composition. Also, the limitations recited in claim 1: ‘provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, and, ‘wherein the composition provides a maximum testosterone concentration Cmax that does not exceed 1500 ng/dL when administered with a meal, are physical properties of the claimed composition.
Accordingly, the oral pharmaceutical composition as taught by the Vies, Lacy and Giliyar, as a whole, where the claimed composition and the prior art composition are structurally indistinguishable, they would share identical functional properties. Thus, the prior art of Vies, Lacy and Giliyar, as a whole, would necessarily provide a self-emulsifying drug delivery system (SEDDS) formulation having an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, a composition that provides a maximum testosterone concentration Cmax that does not exceed 1500 ng/dL when administered with a meal and where the maximum testosterone concentration Cmax is from about 900 ng/dL to about 1100 ng/dL. These properties of the claimed composition would be the natural result of the combination of the prior art elements. Inherency is appropriate in an obviousness analysis "when the limitation(s) at issue is the 'natural result' of the combination of prior art elements." PAR Pharm., Inc. v. TWI Pharms., Inc., 773 F.3d 1186, 1195 (Fed. Cir. 2014) (quoting In re Oelrich, 666 F.2d 578,581 (CCPA 1981)). Therefore, the claimed invention as a whole would have been obvious to one of ordinary skill in view of Vies, Lacy and Giliyar, as a whole.
Double Patenting
(Reformulated and maintained and made again)
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1, 27, 29, 31, 34-36 and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 and 21-30 of U.S. Patent No. 8241664 (herein ‘664) in view of Giliyar et al (US 20100173882, cited in IDS) [Giliyar]. Rejection has been reformulated and made again.
Although the claims at issue are not identical, they are not patentably distinct from each other because Instant Claims and ‘664 claims are directed to common subject matter.
Instant claims are directed to an oral pharmaceutical composition comprising 18 to 22 percent by weight testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, which composition, upon twice-daily oral administration with a meal to a male subject, provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, 1800 ng/dL, or 2500 ng/dL, when administered with a meal.
‘664 claims are directed to a pharmaceutical composition suitable for oral administration comprising 10-20 percent by weight of solubilized testosterone ester; 5-20 percent by weight of hydrophilic surfactant (c) 50-70 percent by weight of lipophilic surfactant; and (d) 10-15 percent by weight of digestible oil, which composition is free of ethanol and exhibits a percent (%) in vitro dissolution profile in phosphate buffered saline, which indicates release from the composition of substantially all of the solubilized testosterone ester within about 2 hours, in which the testosterone ester is testosterone undecanoate
‘644 claims differ from Instant Claims in that the ‘644 claims do not recite orally administering upon twice-daily with a meal to a male subject, provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, from 900-1100 ng/dl, when administered with a meal.
However, Giliyar cures the deficiencies.
Giliyar teaches an oral dosage form comprising testosterone undecanoate ([0006]; [0033-0035]), at least one hydrophilic surfactant and at least one lipophilic surfactant [0033]; [0037], wherein the hydrophilic surfactant is Cremophore RH 40 (Table 5, page 22) and wherein mixtures of surfactants comprising oleic acid (p.23, [0098], left column, Table 8). Particularly, Giliyar teaches that the ratio of lipophilic surfactant (55-70%) to hydrophilic surfactant (10-20%) of about 7:1 to 2.7:1, which would encompass the lipophilic surfactant to hydrophilic surfactant ratio of 6:1 to 3.5:1, as claimed. Further, Giliyar teaches administration of an oral dosage form comprising testosterone undecanoate to an individual upon once a day or twice a day [0036], which composition provides a plasma concentration of testosterone undecanoate at steady state concentration that is between about 200 ng/dL and 1300 ng/dL [0057], of which does not exceed a maximum testosterone concentration of (Cmax) of 1500 ng/dL, 500-1500 ng/dL ([0058]; [0080]; see entire document) of which overlaps with 900-1100 ng/dL.
Accordingly, ‘664 claims in view of Giliyar would provide an identical composition as Instant Claims, so that property of providing an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL with twice daily oral administration with a meal would necessarily result. Accordingly, ‘664 claims in view of Giliyar would provide an identical composition as Instant Claims. Thus, it would have been prima facie obvious to one of ordinary skill in the art to provide the oral pharmaceutical composition of Instant Claims in view of the subject matter as recited in the ‘664 claims and Giliyar, as a whole, at the time the claimed invention was made. Furthermore, U.S. Patent No. 8241664 discloses that formulations have self-emulsifying properties (col.11).
Claims 1, 27, 29, 31, 34-36 and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11179402 (herein ‘402) in view of Giliyar et al (US 20100173882, cited in IDS) [Giliyar]. Rejection has been reformulated and made again.
Although the claims at issue are not identical, they are not patentably distinct from each other because Instant Claims and ‘402 claims are directed to common subject matter.
Instant claims are directed to an oral pharmaceutical composition comprising 18 to 22 percent by weight testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, which composition, upon twice-daily oral administration with a meal to a male subject, provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, 1800 ng/dL, or 2500 ng/dL, when administered with a meal.
‘402 claims are directed to a pharmaceutical composition suitable for oral administration to a mammalian subject, comprising: (a) 10-20 percent by weight of solubilized testosterone ester; (b) 5-20 percent by weight of hydrophilic surfactant (c) 50-70 percent by weight of lipophilic surfactant which is a C14-C24 fatty acid that is oleic acid; wherein said composition further comprises an antioxidant; wherein said composition is free of monohydric alcohol wherein the formulation consists of a liquid encased in a capsule, and wherein administration of the formulation twice daily provides a serum concentration of testosterone ranging from about 300 to about 1100 ng/dL.
‘402 claims differ from Instant Claims in that the ‘402 claims do not recite that the composition provides at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1.
However, Giliyar cures the deficiencies.
Giliyar teaches that the ratio of lipophilic surfactant to hydrophilic surfactant of about 7:1 to 2.7:1, which would encompass the lipophilic surfactant to hydrophilic surfactant ratio of 6:1 to 3.5:1, as claimed. Accordingly, ‘402 claims in view of Giliyar would provide an identical composition as Instant Claims. Thus, it would have been prima facie obvious to one of ordinary skill in the art to provide the oral pharmaceutical composition of Instant Claims in view of the subject matter as recited in the ‘402 claims and Giliyar, as a whole, at the time the claimed invention was made.
Accordingly, ‘402 claims in view of Giliyar would provide an identical composition as Instant Claims, so that property of providing an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL with twice daily oral administration with a meal would necessarily result. Accordingly, ‘402 claims in view of Giliyar would provide an identical composition as Instant Claims. Thus, it would have been prima facie obvious to one of ordinary skill in the art to provide the oral pharmaceutical composition of Instant Claims in view of the subject matter as recited in the ‘664 claims and Giliyar, as a whole, at the time the claimed invention was made. Furthermore, U.S. Patent No. 11179402 discloses that formulations have self-emulsifying properties (col.11).
Claims 1, 27, 29, 31, 34-36 and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10617696 (herein ‘696) in view of Giliyar et al (US 20100173882, cited in IDS) [Giliyar]. Rejection has been reformulated and made again.
Although the claims at issue are not identical, they are not patentably distinct from each other because Instant Claims and ‘696 claims are directed to common subject matter.
Instant claims are directed to an oral pharmaceutical composition comprising 18 to 22 percent by weight testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, which composition, upon twice-daily oral administration with a meal to a male subject, provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, 1800 ng/dL, or 2500 ng/dL, when administered with a meal.
‘696 claims are directed to an oral composition comprising a capsule and a liquid or semi-solid pharmaceutical formulation within the capsule, wherein the pharmaceutical formulation comprises: 19.8 percent by weight of testosterone undecanoate; 51.6 percent by weight of oleic acid; 16.1 percent by weight of polyoxyethylene (40) hydrogenated castor oil; 10 percent by weight of borage seed oil; and 2.5 percent by weight of peppermint oil.
‘696 claims differ from Instant Claims in that the ‘696 claims do not recite that the composition provides at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio falling in the range of about 6:1 to 3.5:1, twice-daily oral administration with a meal to a male subject, and provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, 1800 ng/dL, or 2500 ng/dL, when administered with a meal.
However, Giliyar cures the deficiencies.
Giliyar teaches an oral dosage form comprising testosterone undecanoate, at least one hydrophilic surfactant and at least one lipophilic surfactant wherein the hydrophilic surfactant is Cremophore RH 40 and wherein mixtures of surfactants is provided in a ratio of lipophilic surfactant to hydrophilic surfactant 7:1 to 2.7:1, which would encompass the lipophilic surfactant to hydrophilic surfactant ratio of 6:1 to 3.5:1. Further, Giliyar teaches administration of an oral dosage form comprising testosterone undecanoate to an individual upon twice a day , which composition provides a plasma concentration of testosterone undecanoate at steady state concentration that is between about 200 ng/dL and 1300 ng/dL [0057], of which does not exceed a maximum testosterone concentration of (Cmax) of 1500 ng/dL, 500-1500 ng/dL ([0058]; [0080]; see entire document) of which overlaps with 900-1100 ng/dL
Thus, it would have been prima facie obvious to one of ordinary skill in the art to provide the oral pharmaceutical composition of Instant Claims in view of the subject matter as recited in the ‘696 claims and Giliyar, as a whole, at the time the claimed invention was made. It would have been well within the purview of one of ordinary skill in art to optimize the ratio of the lipophilic surfactant to hydrophilic surfactant to 6:1 to 3.5:1 as taught by Giliyar to achieve optimal solubilization of testosterone undecanoate. Accordingly, ’696 claims in view of Giliyar would provide an identical composition as Instant Claims, so that property of providing an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL with twice daily oral administration with a meal would necessarily result, so that it would necessarily follow that the average serum testosterone concentration in a subject with twice daily oral administration is within the eugonadal range. Furthermore, Instant Claims are open-ended and do not exclude additional, unrecited elements so that the scope of instant claims does not exclude the addition of borage seed oil and peppermint oil. Thus, it would have been prima facie obvious to one of ordinary skill in the art to provide the oral pharmaceutical composition of Instant Claims in view of the subject matter as recited in the ‘696 claims and Giliyar, as a whole, at the time the claimed invention was made. Furthermore, U.S. Patent No. 10617696 discloses that formulations have self-emulsifying properties (col.10).
Claims 1, 6, 8, 27, 28, 29 and 31-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-59 of U.S. Patent No. 8778916 (herein ‘916) in view of Giliyar et al (US 20100173882, cited in IDS) [Giliyar]. Rejection has been reformulated and made again.
Although the claims at issue are not identical, they are not patentably distinct from each other because instant Claims and ‘916 claims are directed to common subject matter.
Instant claims are directed to an oral pharmaceutical composition comprising 18 to 22 percent by weight testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, which composition, upon twice-daily oral administration with a meal to a male subject, provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, 1800 ng/dL, or 2500 ng/dL, when administered with a meal.
‘916 claims are directed to an oral pharmaceutical composition comprising 18-22 percent by weight of solubilized testosterone Undecanoate; 50-55 percent by weight of at least one lipophilic surfactant; and; c. 15-17 percent by weight of at least one hydrophilic surfactant; wherein said lipophilic surfactant is oleic acid.
‘916 claims differ from Instant Claims in that the ‘916 claims do not recite that the composition provides at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, wherein orally administering upon twice-daily with a meal to a subject, provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, 1800 ng/dL, or 2500 ng/dL, when administered with a meal.
However, Giliyar cures the deficiencies.
Giliyar teaches an oral dosage form comprising testosterone undecanoate, at least one hydrophilic surfactant and at least one lipophilic surfactant wherein the hydrophilic surfactant is Cremophore RH 40 and wherein mixtures of surfactants is provided in a ratio of lipophilic surfactant to hydrophilic surfactant 7:1 to 2.7:1, which would encompass the lipophilic surfactant to hydrophilic surfactant ratio of 6:1 to 3.5:1. Further, Giliyar teaches administration of an oral dosage form comprising testosterone undecanoate to an individual upon twice a day , which composition provides a plasma concentration of testosterone undecanoate at steady state concentration that is between about 200 ng/dL and 1300 ng/dL [0057], of which does not exceed a maximum testosterone concentration of (Cmax) of 1500 ng/dL, 500-1500 ng/dL ([0058]; [0080]; see entire document) of which overlaps with 900-1100 ng/dL Moreover, ‘916 claims in view of Giliyar would provide an identical composition as Instant Claims, so that property of providing an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL with twice daily oral administration with a meal would necessarily result. Thus, it would have been prima facie obvious to one of ordinary skill in the art to provide the oral pharmaceutical composition of Instant Claims in view of the subject matter as recited in the ‘916 claims and Giliyar, as a whole, at the time the claimed invention was made. Furthermore, U.S. Patent No. 10617696 discloses that formulations have self-emulsifying properties (col.10).
Claims 1, 6, 8, 27, 28, 29 and 31-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 8778917 (herein ‘917) in view of Giliyar et al (US 20100173882, cited in IDS) [Giliyar]. Rejection has been reformulated and made again.
Although the claims at issue are not identical, they are not patentably distinct from each other because instant Claims and ‘917 claims are directed to common subject matter.
Instant claims are directed to an oral pharmaceutical composition comprising 18 to 22 percent by weight testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, which composition, upon twice-daily oral administration with a meal to a male subject, provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, 1800 ng/dL, or 2500 ng/dL, when administered with a meal.
‘917 claims are directed to an oral pharmaceutical composition consisting essentially of 20% testosterone Undecanoate; polyoxyethylene (40) hydrogenated castor oil (Cremophor RH40); polyoxyethylated apricot kernel oil (Labrafil M1944CS); glyceryl palmitostearate (Precirol ATOS).
‘‘917 claims differ from Instant Claims in that the ‘917 claims do not recite that the composition provides at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, wherein the composition is orally administering upon twice-daily with a meal to a subject that provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, 1800 ng/dL, or 2500 ng/dL, when administered with a meal.
However, Giliyar cures the deficiencies.
Giliyar teaches an oral dosage form comprising testosterone undecanoate, at least one hydrophilic surfactant and at least one lipophilic surfactant wherein the hydrophilic surfactant is Cremophore RH 40 and wherein mixtures of surfactants is provided in a ratio of lipophilic surfactant to hydrophilic surfactant 7:1 to 2.7:1, which would encompass the lipophilic surfactant to hydrophilic surfactant ratio of 6:1 to 3.5:1. Further, Giliyar teaches administration of an oral dosage form comprising testosterone undecanoate to an individual upon twice a day , which composition provides a plasma concentration of testosterone undecanoate at steady state concentration that is between about 200 ng/dL and 1300 ng/dL [0057], of which does not exceed a maximum testosterone concentration of (Cmax) of 1500 ng/dL, 500-1500 ng/dL ([0058]; [0080]; see entire document) of which overlaps with 900-1100 ng/dL Accordingly, ‘917 claims in view of Giliyar would provide an identical composition as Instant Claims, so that property of providing an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL with twice daily oral administration with a meal would necessarily result, so that it would necessarily follow that the average serum testosterone concentration in a subject with twice daily oral administration is within the eugonadal range. Furthermore, Instant Claims are open-ended and do not exclude additional, unrecited elements so that the scope of instant claims does not exclude the addition of polyoxyethylated apricot kernel oil (Labrafil M1944CS); glyceryl palmitostearate (Precirol ATOS). Furthermore, U.S. Patent No. 8778917 discloses that formulations have self-emulsifying properties (col.11).
Claims 1, 6, 8, 27, 28, 29 and 31-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 8492369 (herein ‘369) in view of Giliyar et al (US 20100173882, cited in IDS) [Giliyar]. Rejection has been reformulated and made again.
Although the claims at issue are not identical, they are not patentably distinct from each other because instant Claims and ‘369 claims are directed to common subject matter.
Instant claims are directed to an oral pharmaceutical composition comprising 18 to 22 percent by weight testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, which composition, upon twice-daily oral administration with a meal to a male subject, provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, 1800 ng/dL, or 2500 ng/dL, when administered with a meal.
‘369 claims are directed to an n oral pharmaceutical composition comprising 18-22 percent by weight of solubilized testosterone undecanoate; 50-55 percent by weight of at least one lipophilic surfactant; percent by weight of at least one hydrophilic surfactant; and percent by weight of a mixture of borage seed oil and peppermint oil wherein said hydrophilic surfactant is polyoxyethylene(40)hydrogenated castor oil, wherein said lipophilic surfactant is oleic acid, wherein upon once- or twice-daily oral administration, provides an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL; wherein the ratio of lipophilic surfactants to hydrophilic surfactants is about 4:1.
‘369 claims differ from Instant Claims in that the ‘369 claims do not recite that the composition provides at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1.
However, Giliyar cures the deficiencies.
Giliyar teaches an oral dosage form comprising testosterone undecanoate, at least one hydrophilic surfactant and at least one lipophilic surfactant wherein the hydrophilic surfactant is Cremophore RH 40 and wherein mixtures of surfactants is provided in a ratio of lipophilic surfactant to hydrophilic surfactant 7:1 to 2.7:1, which would encompass the lipophilic surfactant to hydrophilic surfactant ratio of 6:1 to 3.5:1. Further, Giliyar teaches administration of an oral dosage form comprising testosterone undecanoate to an individual upon twice a day , which composition provides a plasma concentration of testosterone undecanoate at steady state concentration that is between about 200 ng/dL and 1300 ng/dL [0057], of which does not exceed a maximum testosterone concentration of (Cmax) of 1500 ng/dL, 500-1500 ng/dL ([0058]; [0080]; see entire document) of which overlaps with 900-1100 ng/dL . Accordingly, ‘369 claims in view of Giliyar would provide an identical composition as Instant Claims, so that property of providing an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL with twice daily oral administration with a meal would necessarily result, so that it would necessarily follow that the average serum testosterone concentration in a subject with twice daily oral administration is within the eugonadal range.
Thus, it would have been prima facie obvious to one of ordinary skill in the art to provide the oral pharmaceutical composition of Instant Claims in view of the subject matter as recited in the ‘396 claims and Giliyar, as a whole, at the time the claimed invention was made. Furthermore, U.S. Patent No. 10617696 discloses that formulations have self-emulsifying properties (col.10).
Claims 1, 6, 8, 27, 28, 29 and 31-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 8828428 (herein ‘428) in view of Vies (USP 4147783, cited in IDS) [Vies] and Giliyar et al (US 20100173882, cited in IDS) [Giliyar]. Rejection has been reformulated and made again.
Although the claims at issue are not identical, they are not patentably distinct from each other because instant Claims and ‘428 claims are directed to common subject matter.
Instant claims are directed to an oral pharmaceutical composition comprising 18 to 22 percent by weight testosterone undecanoate solubilized in a carrier comprising at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, which composition, upon twice-daily oral administration with a meal to a male subject, provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, 1800 ng/dL, or 2500 ng/dL, when administered with a meal.
‘428 claims are directed to an oral pharmaceutical composition consisting essentially of 10% to 20% testosterone Undecanoate; polyoxyethylene (40) hydrogenated castor oil (Cremophor RH40); a lipophilic surfactant chosen from mono- and/or di-glycerides of fatty acids and polyethylene glycol with an average molecular weight of about 200 to about 10,000 g/mol, wherein said composition is free of ethanol, wherein said mono and/or di-glycerides of fatty acids is chosen from Precirol ATO 5 (glyceryl palmitostearate) and Maisine (glyceryl mono-linoleate).
‘428 claims differ from Instant Claims in that the ‘917 claims do not recite that the composition provides at least one lipophilic surfactant and at least one hydrophilic surfactant in a total lipophilic surfactant to total hydrophilic surfactant ratio (w/w) falling in the range of about 6:1 to 3.5:1, wherein the lipophilic surfactant is oleic acid, wherein orally administering upon twice-daily with a meal to a subject, provides an average serum testosterone concentration (Cavg) at steady state in the subject within the eugonadal range, wherein the composition provides a maximum testosterone concentration (Cmax) that does not exceed 1500 ng/dL, 1800 ng/dL, or 2500 ng/dL, when administered with a meal.
However, Vies and Giliyar, as a whole, cure the deficiencies.
Vies teaches an oral pharmaceutical composition an effective amount of a pharmaceutical preparation comprising testosterone undecanoate, in combination with a lipoid, wherein the lipoid substance (i.e., lipophilic surfactant) is selected from oleic acid and mono- and/or di-glycerides of fatty acids, wherein the lipoid substance is preferably oleic acid. Thus, it would have been obvious to modify ‘428 claims in view of Vies to substitute or further comprise oleic acid as a lipophilic surfactant for di-glycerides of fatty acids as recited in the ‘428 claims to provide an lipophilic surfactant that is oleic acid in accordance with Instant claims having a reasonable expectation of success.
Giliyar teaches an oral dosage form comprising testosterone undecanoate, at least one hydrophilic surfactant and at least one lipophilic surfactant wherein the hydrophilic surfactant is Cremophore RH 40 and wherein mixtures of surfactants is provided in a ratio of lipophilic surfactant to hydrophilic surfactant 7:1 to 2.7:1, which would encompass the lipophilic surfactant to hydrophilic surfactant ratio of 6:1 to 3.5:1. Further, Giliyar teaches administration of an oral dosage form comprising testosterone undecanoate to an individual upon twice a day , which composition provides a plasma concentration of testosterone undecanoate at steady state concentration that is between about 200 ng/dL and 1300 ng/dL [0057], of which does not exceed a maximum testosterone concentration of (Cmax) of 1500 ng/dL, 500-1500 ng/dL ([0058]; [0080]; see entire document) of which overlaps with 900-1100 ng/dL Moreover, ‘428 claims in view of Giliyar would provide an identical composition as Instant Claims, so that property of providing an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL with twice daily oral administration with a meal would necessarily result, so that it would necessarily follow that the average serum testosterone concentration in a subject with twice daily oral administration is within the eugonadal range. Furthermore, Instant Claims are open-ended and do not exclude additional, unrecited elements so that the scope of instant claims does not exclude the addition of polyethylene glycol with an average molecular weight of about 200 to about 10,000 g/mol, Precirol ATO 5 (glyceryl palmitostearate) and Maisine (glyceryl mono-linoleate)., Thus, it would have been prima facie obvious to one of ordinary skill in the art to provide the oral pharmaceutical composition of Instant Claims in view of the subject matter as recited in the ‘428 claims, Vies and Giliyar, as a whole, at the time the claimed invention was made. Furthermore, U.S. Patent No. 8828428 discloses that formulations have self-emulsifying properties (col.11).
Response to Arguments
Applicants argue:
Claims 1, 6, 8, 27-29, and 31-41 were rejected on the ground of nonstatutory double patenting as allegedly being unpatentable over Claims 1-16 and 21-30 of U.S. Patent No. 8,241,664 (hereinafter "US '664") in view of Giliyar, Liao, and Wacher.
Herein, the reformulated rejections are maintained and made again, as set forth above.
Claims 1, 6, 8, 27-29, and 31-41 were also rejected on the ground ofnonstatutory double patenting as allegedly being unpatentable over Claim 1 of U.S. Patent No. 10,617,696 (hereinafter "'696") in view of Giliyar, Liao, and Wacher.
Herein, the reformulated rejections are maintained and made again, as set forth above.
Claims 1, 6, 8, 27-29, and 31-41 were also rejected on the ground ofnonstatutory double patenting as allegedly being unpatentable over Claims 1-59 of U.S. Patent No. 8,778,916 (hereinafter "'916") in view of Giliyar, Liao, and Wacher.
Herein, the reformulated rejections are maintained and made again, as set forth above.
Claims 1, 6, 8, 27-29, and 31-41 were also rejected on the ground ofnonstatutory double patenting as allegedly being unpatentable over Claims 1-9 of U.S. Patent No. 8,778,917 (hereinafter "'917") in view of Giliyar, Liao, and Wacher.
Herein, the reformulated rejections are maintained and made again, as set forth above.
Claims 1, 6, 8, 27-29, and 31-41 were also rejected on the ground ofnonstatutory double patenting as allegedly being unpatentable over Claims 1-6 of U.S. Patent No. 8,492,369 (hereinafter "'369") in view of Giliyar, Liao, and Wacher.
Herein, the reformulated rejections are maintained and made again, as set forth above.
Claims 1, 6, 8, 27-29, and 31-41 were also rejected on the ground ofnonstatutory double patenting as allegedly being unpatentable over Claims 1-6 of U.S. Patent No. 4,147,783 (hereinafter "'783") in view of Giliyar, Liao, and Wacher.
Herein, the reformulated rejections are maintained and made again, as set forth above
Applicants argue:
As detailed above and in the Previous Response, the instantly claimed TU compositions are surprisingly superior for treating testosterone deficiency, achieving an enhanced dissolution profile and providing consistent levels of T over time that results in an average serum T concentration in the eugonadal range. Each of these benefits, alone or in combination, render the instantly claimed composition significantly improved relative to alternative TU compositions such as Andriol® Testocaps®, which improvements are unexpected. Indeed, as detailed above and in the Previous Response, these improvements are even more unexpected in view of the data in Giliyar. Thus, the instantly claimed compositions support unexpected results.
Accordingly, claims 1, 18, 22, 27, 29, 31, 34-36, and 41 are patentable over Claims 1-16 and 21-30 of US '664, Claim 1 of '696, Claims 1-59 of '916, Claims 1-9 of '917, Claims 1-6 of '369, and Claims 1-6 of '783 in view of Giliyar, Liao, and Wacher, and Applicant respectfully requests acknowledgement of same. Claims 6, 8, 28, 32, 33, and 37-40 have been canceled herein, without prejudice, thereby rendering the rejection moot with respect to those claims.
Applicant’s arguments have been fully considered but they are not persuasive, because the unexpected results are not commensurate in scope with what is instantly claimed, because the scope of Instant Claims would encompass, at least, one or more lipophilic surfactant(s) and/or hydrophilic surfactant(s) described in Applicants’ Specification in para. [0037-0045] and mixture thereof [0046], as discussed above. The scope of the showing must be commensurate with the scope of claims to consider evidence probative of unexpected results. Therefore, the probative value of the data is not commensurate in scope with the degree of protection sought by the claim(s).
Therefore, all of Double Patenting Rejections are maintained and made again.
Conclusions
No claim is allowed.
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/T.W./ Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
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