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 .1
Reopening of Prosecution After Appeal Brief
In view of the Appeal Brief filed on Nov 12 2025, PROSECUTION IS HEREBY REOPENED. A new ground of rejection is set forth below.
To avoid abandonment of the application, appellant must exercise one of the following two options:
(1) file a reply under 37 CFR 1.111 (if this Office action is non-final) or a reply under 37 CFR 1.113 (if this Office action is final); or,
(2) initiate a new appeal by filing a notice of appeal under 37 CFR 41.31 followed by an appeal brief under 37 CFR 41.37. The previously paid notice of appeal fee and appeal brief fee can be applied to the new appeal. If, however, the appeal fees set forth in 37 CFR 41.20 have been increased since they were previously paid, then appellant must pay the difference between the increased fees and the amount previously paid.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below:
/ADAM C MILLIGAN/ Supervisory Patent Examiner, Art Unit 1623
Status of Claims
Claims 1-20 are pending. As discussed below claims 1-5, 8-12, 14 and 18-20 are under examination, as directed to Example 1 of Table 1, including previously withdrawn claim 3 directed to microcrystalline cellulose, MCC. Claim 6, 7, 15-17 are withdrawn. Withdrawn claim 13 has been rejoined. Claims 11-13 are allowable.
Terminal Disclaimer
The terminal disclaimer filed on Nov 12, 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of 17,765,934 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Response to Arguments
Applicant's arguments filed Nov 12, 2025 have been fully considered but they are not persuasive. Claims 1, 3, 4, 5, 8-10, 14, 19 and 20 remain rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/043208 A1 (WO 208). See below.
Also note new rejections of claim 2 and 18 below, necessitating the reopening of prosecution.
Maintained Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3, 4, 5, 8-10, 14, and 18-20 remain rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/043208 A1 (“WO 208” – cited on 7/2/2024 IDS, 2nd FOR reference).
Examined claim 1 requires a tablet formulation of a granulate co-precipitate of enzalutamide (ENZ) in amorphous form and a cellulosic concentration enhancing polymer selected from hydroxypropylmethylcellulose acetate succinate (HPMCAS) and hydroxypropylmethylcellulose phthalate (HPMCP); a substrate comprising a sugar alcohol (mannitol), microcrystalline cellulose, (MCC), or mixtures thereof, where the weight ratio of enzalutamide to polymer is in the range of 1 : 2 : 0.5 to 1: 6 : 5, respectively.
In terms of claim interpretation, the specification teaches co-precipitation of enzalutamide (ENZ) and a polymer (such HMPCAS) at step a) of the process of page 9. See also claim 11, step a). While the specification notes the tablet comprises a granulate formed by co-precipitation of ENZ and HMPCAS, claim 1 is interpreted to be a tablet formulation comprising a granulate (whether formed by the art recognized process of co-precipitation or not), with the required enzalutamide in granule with a polymer (HPMCAS) and a substrate of microcrystalline cellulose (MCC) in the claimed ratio range of 1 : 2 : 0.5 to 1: 6 : 5, respectively.
Further, the specification recognizes the unique challenges of formulating enzalutamide, where it states “Enzalutamide is a BCS class II2 compound, exhibiting low solubility [in water, i.e., aqueous solvents] and high permeability [easily pass thru cell membranes and are easily absorbed by the body].” See specification at page 2, lines 5-6.
Prior art recognizing these tablet limitations and recognizing the unique challenges of formulating enzalutamide tablets would have been relevant to a person having ordinary skill in the art (PHOSITA) in the obviousness analysis.
To address the recognized low solubility issue, WO 208 teaches formulating “a suitable single tablet of reasonable size comprising the prescribed amount of enzalutamide and having suitable and advantageous solubility and/or dissolution stability and absorption would be advantageous as a suitable alternative to soft capsules.” Id. at paragraph 5.
As required by claim 1’s co-precipitate limitation, WO 208 teaches a enzalutamide (amorphous form) dissolved in solvent with a polymer such as HPMCAS in the presence of a substrate, MCC, in tablet form, where the taught ENZ : HPMCAS (polymer) : MCC (substrate) ratio falls with the range of claim 1. See Example 14, Table 14.1 on page 64 reproduced below.
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While not specifically recited by claim 1, it is noted that ENZ and the concentration enhancing polymer HPMCAS component of claim 1 is formed by dissolving both in acetone. See page 9, step a) of the process recited therein. See also process claim 11, step a).
Similar to this process, WO 208 recognized the solubility issue of enzalutamide, dissolves it with acetone, and/or mixtures with water. See paragraphs 79, 145, and Example 2 entitled (Preparation of enzalutamide dispersions with concentration enhancing polymers [example used therein HPMCAS].
The below claim chart highlights examined claim 1’s limitations and how they are taught by Table 14.1 of WO 208.
Instant Claim 1 Limitations
Table 14.1. Tablet Composition
tablet composition comprising
a granulate consisting of a co-precipitate (comprises amorphous enzalutamide (ENZ) and a polymer, hydroxypropylmethylcellulose acetate succinate (HPMCAS) on a substrate
266.7 grams of 60% amorphous (A) enzalutamide(ENZ) / HPMCAS-M-SDD (spray dry dispersions)
The ENZ SDD was formed dissolving it with acetone along with the polymer HPMCAS, as per claims 36, 37 and 38.
wherein the substrate comprises a sugar alcohol, microcrystalline cellulose, or
mixtures thereof; and
See Example 14, Table 14.1 noting the presence of 94.8 grams microcrystalline cellulose (MCC, aka Avicel® PH102)
wherein the weight ratio of enzalutamide to the cellulosic concentration enhancing polymer to the substrate is within the range of 1:2:0.5 to 1:6:5, respectively.
See Table 14.1 with 60% of enzalutamide, or 160.2 grams (60% of 267.7 grams total) with
106.8 grams of the polymer HPMCAS (40% of 267.7 grams total) with
94.8 grams microcrystalline cellulose substrate in a weight ratio as follows,
160.2 g ENZ : 106.8 g HPMCAS : 94.8 g MCC
This ratio of about 1.6 : 1 : 0.95 (or about 1 : 0.67 : 0.67) is in contrast to the claimed ratio of claim 1. 1 : 2 : 0.5 to 1 :6 : 5.
While Table 14.1 does not teach the exact ratio of ENZ : polymer (e.g., HPMCAS or HPMCP) : substrate as claimed, per MPEP 2144.05 I.-II.3, it would be prima facie obvious for a PHOSITA to adjust the ranges of the particular ratios of ENZ : polymer ratio as taught WO 208. Paragraph 88 of WO 208 teaches such adjustment of range, as well as a basis to adjust such ranges as follows.
“[t]he amount of concentration-enhancing polymer relative to the amount of enzalutamide present in the dispersions may vary widely. The composition of enzalutamide/polymer dispersions is expressed, for example, as 25%A:HPMCAS-M, where 25%A means "25% active" and the dispersion contains 25% (by weight) enzalutamide and 75% (by weight) hydroxypropylmethylcellulose acetate succinate M-grade. In enzalutamide dispersions described herein, the enzalutamide content is generally greater than 20%A; in some embodiments, from 25%A to 75%A; in some embodiments, from 50%A to 70%A. For a specific concentration-enhancing polymer, the enzalutamide/polymer ratio that yields optimum results is best determined in in vitro dissolution tests and/or in vivo bioavailability tests.
Note, where WO 208, paragraph 88, teaches an ENZ: polymer ratio 25%: 75% or 1:3 falls within the claimed range ratio of ENZ to HPMCA.
While Table 14.1 does not teach a granulate co-precipitate of amorphous enzalutamide and a polymer such as HPMCAS with other excipients, a PHOSITA would formulate such a granulate so with a reasonable expectation of success as it discloses granules for formulation into tablets as taught in WO 208 as follows.
WO 208 claim 95 teaches a process for manufacturing enzalutamide and polymer tablets where (1) a solid dispersion of enzalutamide and polymer is formed, (2) the solid dispersion of enzalutamide and polymer is mixed with additives to form a granulating mixture and (3) tableting the mixture.
Further, WO 208 teaches its spray dried dispersion post solidification, stays as a solid powder in its spray drying chamber to further evaporate solvent from it. See paragraph 81. Subsequently, the dried powder is preferably sprayed with a solvent or polymer solution or other excipient to form granules. Id. at paragraph 81. Note that paragraph 81 discloses the spraying of polymer or other excipient into the spraying drying chamber to form granules, where it would be with the purview of a PHOSITA to routinely optimize a spraying of a co-precipitate of polymer, ENZ and substate, where the ENZ and polymer co-precipitate when sprayed with a substate would form the claimed granulate consisting of a co-precipitate on a substrate.
Alternatively, the tablet formulation of Table 14.1, while being a dry powder direct compression, methods of forming solid pharmaceutical composition as granulate via dry granulation are also routine for a PHOSITA to routinely optimize to predictably arrive at the claimed invention. See paragraph 151. The granulate of claims 1 and 14, consisting of a co-precipitate on a substrate, could be formed by the dry granulation of paragraph 151, where the dry mixing and granulation of co-precipitate with a excipient/substrate would result in the claimed granulate consisting of co-precipitate on a substrate.
A PHOSITA would routinely optimize the teachings of Table 14.1 as per the granulation methods of as per claim 95 and paragraphs 81 and 151.
At the time the present application was filed, it would have been prima facie obvious to a PHOSITA following the teachings of WO 208 to have 1) arrived at the claimed enzalutamide: polymer : substrate and 2) to formulate the composition of WO 208’s Table 14.1 via dry granulation as claimed in order to arrive at the tablet formulation of instant claim 1. A rationale to do so would be the combination of prior art elements (teachings of tablet of Table 14.1) combined with known methods (adjust of ranges ENZ and polymer, and known methods to granulate to form solid dosage forms such as tablet compression) to predictably arrive at the claimed invention.
Regarding claim 3 and the limitation of microcrystalline cellulose as a substrate, WO 208 teaches MCC at Table 14.1 as discussed above.
Regarding claims 4-5 and the limitation of disintegrant, such as croscarmellose sodium, this is taught by WO 208 in Table 14.1.
Regarding claims 8-9 and the limitations of where the tablet further comprises a pharmaceutically acceptable excipient, such as diluents, disintegrants, glidants and lubricants, these limitations are taught by WO 208 in Table 14.1.
WO 208 teaches that examples of diluents include these two ingredients of Table 14.1, lactose. See paragraph 124.
WO 208 teaches that colloidal silicon dioxide of Table 14.1 is a glidant. See paragraphs 93 and 119.
WO 208 teaches croscarmellose sodium of Table 14.1 is a disintegrant. See claim 33.
WO 208 teaches the known lubricant, magnesium stearate of Table 14.1. See paragraph 115 for examples of lubricant including Mg stearate.
Regarding claim 10 and the dissolution rate properties recited therein, WO 208 does not teach this limitation that further limits the tablet of claim 1.
However, per MPEP 2112.01 II.4, “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.” citing In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
As WO 208 teaches the claimed tablet of claim 1, the dissolution rate properties of claim 10 are necessarily present in its tablet formulation of Table 14.1.
Regarding claim 14 and its granulate consisting of a co-precipitate on a substrate, as detailed above, WO 208 discloses such a granulate as detailed in the claim chart comparing claim 1 to Table 14.1, where each of the elements of the granulate of claim 14 is disclosed, such as ENZ, HPMCAS and a surfactant such as MCC, in the claimed weight ratio.
Instant Claim 1 Limitations
Table 14.1. Tablet Composition
tablet composition comprising
a granulate consisting of a co-precipitate (comprises amorphous enzalutamide (ENZ) and a polymer, hydroxypropylmethylcellulose acetate succinate (HPMCAS) on a substrate
266.7 grams of 60% amorphous (A) enzalutamide(ENZ) / HPMCAS-M-SDD (spray dry dispersions)
The ENZ SDD was formed dissolving it with acetone along with the polymer HPMCAS, as per claims 36, 37 and 38.
wherein the substrate comprises a sugar alcohol, microcrystalline cellulose, or
mixtures thereof; and
See Example 14, Table 14.1 noting the presence of 94.8 grams microcrystalline cellulose (MCC, aka Avicel® PH102)
wherein the weight ratio of enzalutamide to the cellulosic concentration enhancing polymer to the substrate is within the range of 1:2:0.5 to 1:6:5, respectively.
See Table 14.1 with 60% of enzalutamide, or 160.2 grams (60% of 267.7 grams total) with
106.8 grams of the polymer HPMCAS (40% of 267.7 grams total) with
94.8 grams microcrystalline cellulose substrate in a weight ratio as follows,
160.2 g ENZ : 106.8 g HPMCAS : 94.8 g MCC
This ratio of about 1.6 : 1 : 0.95 (or about 1 : 0.67 : 0.67) is in contrast to the claimed ratio of claim 1. 1 : 2 : 0.5 to 1 :6 : 5.
While Table 14.1 does not teach the exact ratio of ENZ : polymer (e.g., HPMCAS or HPMCP) : substrate as claimed, per MPEP 2144.05 I.-II.5, it would be routine for a PHOSITA to adjust the ranges of the particular ratios of ENZ : polymer ratio as taught WO 208. Paragraph 88 of WO 208 teaches such adjustment of range, as well as a basis to adjust such ranges as follows.
“[t]he amount of concentration-enhancing polymer relative to the amount of enzalutamide present in the dispersions may vary widely. The composition of enzalutamide/polymer dispersions is expressed, for example, as 25%A:HPMCAS-M, where 25%A means "25% active" and the dispersion contains 25% (by weight) enzalutamide and 75% (by weight) hydroxypropylmethylcellulose acetate succinate M-grade. In enzalutamide dispersions described herein, the enzalutamide content is generally greater than 20%A; in some embodiments, from 25%A to 75%A; in some embodiments, from 50%A to 70%A. For a specific concentration-enhancing polymer, the enzalutamide/polymer ratio that yields optimum results is best determined in in vitro dissolution tests and/or in vivo bioavailability tests.
Note, where WO 208, paragraph 88, teaches an ENZ: polymer ratio 25%: 75% or 1:3 falls within the claimed range ratio of ENZ to HPMCA.
While Table 14.1 does not teach a granulate co-precipitate of amorphous enzalutamide and a polymer such as HPMCAS with other excipients, a PHOSITA would formulate such a granulate so with a reasonable expectation of success as it discloses granulates for formulation into tablets as taught in WO 208 as follows.
WO 208 claim 95 teaches a process for manufacturing enzalutamide and polymer tablets where (1) a solid dispersion of enzalutamide and polymer is formed, (2) the solid dispersion of enzalutamide and polymer is mixed with additives to form a granulating mixture and (3) tableting the mixture.
Further, WO 208 teaches its spray dried dispersion post solidification, stays as a solid powder in its spray drying chamber to further evaporate solvent from it. See paragraph 81. Subsequently, the dried powder is preferably sprayed with a solvent or polymer solution or other excipient to form granules. Id. at paragraph 81. Note that paragraph 81 discloses the spraying of polymer or other excipient into the spraying drying chamber to form granulate, where it would be with the purview of a PHOSITA to routinely optimize a spraying of a co-precipitate of polymer, ENZ and substate, where the ENZ and polymer co-precipitate when sprayed with a substate would form the claimed granulate consisting of a co-precipitate on a substrate.
Alternatively, the tablet formulation of Table 14.1, while being a dry powder direct compression, methods of forming solid pharmaceutical composition as granules via dry granulation are also routine for a PHOSITA to routinely optimize to predictably arrive at the claimed invention. See paragraph 151.
The granulate of claims 1 and 14, consisting of a co-precipitate on a substrate, could be formed by the dry granulation of paragraph 151, where the dry mixing and granulation of co-precipitate with a excipient/substrate would result in the claimed granulate consisting of co-precipitate on a substrate.
A PHOSITA would routinely optimize the teachings of Table 14.1 as per the granulation methods of as per claim 95 and paragraphs 81 and 151.
At the time the present application was filed, it would have been prima facie obvious to a PHOSITA following the teachings of WO 208 to have 1) arrived at the claimed enzalutamide: polymer : substrate and 2) to formulate the composition of Table 14.1 via dry granulation as claimed in order to arrive at the tablet formulation of claim 1. A rationale to do so would be the combination of prior art elements (teachings of tablet of Table 14.1) combined with known methods (adjust of ranges ENZ and polymer, and known methods to granulate to form solid dosage forms such as tablet compression) to predictably arrive at the claimed invention.
Claim 18 is directed to the granulate wherein the weight ratio of enzalutamide: polymer: substrate is 1:3:1 to 1:5:3, respectively.
This ratio of about 1.6 : 1 : 0.95 (or about 1 : 0.67 : 0.67) is taught above, see Table 14.1.
While Table 14.1 does not teach the exact ratio of ENZ : polymer (e.g., HPMCAS or HPMCP) : substrate as claimed, per MPEP 2144.05 I.-II.6, it would be routine for a PHOSITA to adjust the ranges of the particular ratios of ENZ : polymer ratio as taught WO 208. Paragraph 88 of WO 208 teaches such adjustment of range, as well as a basis to adjust such ranges as follows.
“[t]he amount of concentration-enhancing polymer relative to the amount of enzalutamide present in the dispersions may vary widely. The composition of enzalutamide/polymer dispersions is expressed, for example, as 25%A:HPMCAS-M, where 25%A means "25% active" and the dispersion contains 25% (by weight) enzalutamide and 75% (by weight) hydroxypropylmethylcellulose acetate succinate M-grade. In enzalutamide dispersions described herein, the enzalutamide content is generally greater than 20%A; in some embodiments, from 25%A to 75%A; in some embodiments, from 50%A to 70%A. For a specific concentration-enhancing polymer, the enzalutamide/polymer ratio that yields optimum results is best determined in in vitro dissolution tests and/or in vivo bioavailability tests.
Note, where WO 208, paragraph 88, teaches an ENZ: polymer ratio 25%: 75% or 1:3 falls within the claimed range ratio of ENZ to HPMCA.
While Table 14.1 does not teach a granulate co-precipitate of amorphous enzalutamide and a polymer such as HPMCAS with other excipients, a PHOSITA would formulate such a granulate so with a reasonable expectation of success as it discloses granulates for formulation into tablets as taught in WO 208 as follows.
WO 208 claim 95 teaches a process for manufacturing enzalutamide and polymer tablets where (1) a solid dispersion of enzalutamide and polymer is formed, (2) the solid dispersion of enzalutamide and polymer is mixed with additives to form a granulating mixture and (3) tableting the mixture.
Further, WO 208 teaches its spray dried dispersion post solidification, stays as a solid powder in its spray drying chamber to further evaporate solvent from it. See paragraph 81. Subsequently, the dried powder is preferably sprayed with a solvent or polymer solution or other excipient to form granules. Id. at paragraph 81. Note that paragraph 81 discloses the spraying of polymer or other excipient into the spraying drying chamber to form granulate, where it would be with the purview of a PHOSITA to routinely optimize a spraying of a co-precipitate of polymer, ENZ and substate, where the ENZ and polymer co-precipitate when sprayed with a substate would form the claimed granulate consisting of a co-precipitate on a substrate.
Alternatively, the tablet formulation of Table 14.1, while being a dry powder direct compression, methods of forming solid pharmaceutical composition as granules via dry granulation are also routine for a PHOSITA to routinely optimize to predictably arrive at the claimed invention. See paragraph 151.
The granulate of claims 1 and 14, consisting of a co-precipitate on a substrate, could be formed by the dry granulation of paragraph 151, where the dry mixing and granulation of co-precipitate with a excipient/substrate would result in the claimed granulate consisting of co-precipitate on a substrate.
A PHOSITA would routinely optimize the teachings of Table 14.1 as per the granulation methods of as per claim 95 and paragraphs 81 and 151.
Regarding claim 19 and the limitation the ENZ tablet comprising the granulate of claim 14, the claimed ENZ tablet and granulate are rendered obvious as explained in the rejection of claims 1 and 14. With regard to the limitations of one or more extragranular excipients (diluents, disintegrants and lubricants), Table 14.1 teaches these excipients as follows.
WO 208 teaches that examples of diluents include these two ingredients of Table 14.1, lactose. See paragraph 124.
WO 208 teaches that colloidal silicon dioxide of Table 14.1 is a glidant. See paragraphs 93 and 119.
WO 208 teaches croscarmellose sodium of Table 14.1 is a disintegrant. See claim 33.
WO 208 teaches the known lubricant, magnesium stearate of Table 14.1. See paragraph 115 for examples of lubricant including Mg stearate.
Regarding claim 20 and the dissolution rate properties recited therein, WO 208 does not teach this limitation that further limits the tablet of claim 19.
However, per MPEP 2112.01 II.7, “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.” citing In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
As WO 208 teaches the claimed tablet of claim 19, the dissolution rate properties of claim 20 are necessarily present in its tablet formulation of Table 14.1.
Consistent with the non-final office action, claims 11-13, directed to process claims, remain free of the closest prior art, WO ‘208, of this obviousness rejection.
Claims 1-5, 8-10, 14, and 18-20 remain rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/043208 A1 (“WO 208”) reference in view of WO 2008064202A2 (“WO 202”).
WO 208 is cited on the 7/2/2024 IDS, 2nd FOR WO 202 is cited on the PTO 892 form.
While WO 208 teaches the limitations of claims 1, 3-5, 8-10, 14, and 18-20 as detailed above, it does not teach claim 2 and where the species of sugar alcohol component of the substrate is mannitol.
Mannitol as a substrate of co-precipitation process is well known. See WO 202 page 8, lines 11-16. Note that WO 202 discloses “Other hydrophilic or hydrophobic materials acceptable for the preparation of solid dispersions are well within the scope of this invention without limitation as long as these materials improve the solubility properties of the active.” See page 8, lines 19-22.
At the time the present application was filed, it would have been prima facie obvious to a PHOSITA following the teachings of WO 208 to have 1) arrived at the claimed enzalutamide: polymer : substrate and 2) to formulate the composition of WO 208’s Table 14.1 via dry granulation as claimed in order to arrive at the tablet formulation of instant claim 1, where 3) the art discloses mannitol is known to be co-precipitation substrate. A rationale to do so would be the combination of prior art elements (teachings of tablet of Table 14.1) combined with known methods (adjust of ranges ENZ and polymer, and known methods to granulate to form solid dosage forms such as tablet compression), where mannitol is known as a co-precipitation substrate, to predictably arrive at the claimed invention.
Response to Argument:
Initially it is noted that process claims 11-13 are allowable. Therefore, a composition or product by the allowed process of making would similarly be allowable.
Starting at page 4 of the Appeal Brief, Applicant arguments can be summarized as follows: Starting at page 7, Applicant argues that with regard to broadest reasonable claim construction the Examiner’s claim construction seeks to ignore Applicant’s claim language and relationship that it requires, while not staying true to the claim language naturally aligned with the patent’s description. See page 10 of Appeal Brief.
Applicant states:
The dry granulation granules proposed by the Examiner do not have a co-precipitate on a substrate. And the dry granulation granulates used to incorporate a spray-dried
dispersion are different from and distinguished from the inventive granulate. A worker skilled in the art could not reasonably find that the very granulate criticized by the applicant was nonetheless covered by the claim language. Accordingly, the Examiner's claim construction is unreasonably broad and should be reversed. Id. at page 10.
Applicant argues, while not explicitly stating the language of “product by process” that specific product composition claimed, is limited in essence by the invention’s process, where, the claimed invention is limited by the process of incorporating solid dispersion particles into a granulate. Id. at page 7 of the Appeal Brief, where the Attorney argues proper weight needs to be given the term “co-precipitate” “on” a “substrate” (i.e. formed by a process of co-precipitation ). See also page 8 of the Appeal Brief, where it states the claimed invention is specifically limited as a product by process, where “[t]he result of this process places the co-precipitate on the substrate. . . . “ where the “structural relationship of the co-precipitate on the substrate” is limited to the process, that is consistent with and “supported by, the disclosed method of making the granulate.”
The Attorney states it has distinguished the present invention form granules made with spray dried solid dispersions via dry granulation.
In response, as noted above, WO 208 teaches methods granulation as per claim 95 and paragraphs 81 and 151. Note that unlike claim 11 (process NOT rejected for obviousness over WO 208), there is no explicit limitation requiring a spraying on (deposited step), but rather a co-precipitate on a substrate. Note that paragraph 81 discloses the spraying of polymer or other excipient into the spraying drying chamber to form granules, where it would be with the purview of a PHOSITA to routinely optimize a spraying of a co-precipitate of polymer, ENZ and substate, where the ENZ and polymer co-precipitate when sprayed with a substate would form the claimed granulate consisting of a co-precipitate on a substrate. Further, the granulate of claims 1 and 14, consisting of a co-precipitate on a substrate, could be formed by the dry granulation of paragraph 151, where the dry mixing and granulation of co-precipitate with a excipient/substrate would result in the claimed granulate consisting of co-precipitate on a substrate.
As noted ,process claim 11 and claims dependent are allowable. Applicant states, there is “No Prima Facie Case of Obviousness Under Correction Construction,” arguing “the claimed granulate as properly construed is not taught or suggested by the dry granulation disclosure of spray dried dispersions in WO 208.” See page 10 of the Appeal Brief.
However, it is noted that claims directed either to the claimed tablet or claimed granulate, do not explicitly recite the allowable process steps of claim 11.
Applicant states the “Examiner’s Alternative Theory” also relies upon paragraph 81 of WO 208 to suggest the claimed granulate. Applicant states the Examiner is mistaken as paragraph 81 related to further removing residual solvent form the solid dispersion before exiting the spray dryer apparatus, not to spray a solvent/solution of polymer or other excipient into the spray drying chamber to form granules.
Applicant states that based on the spray drier used in WO 208, the process is dubious stating that adding a polymer solution would result in polymer particles, not a coating of polymer on the previously produced dispersion, as claimed the Examiner. See page 11 of Appeal Brief, citing to footnote 25. See also statements on page 11 of the Appeal Brief arguing subsequent spray drying of enzalutamide/polymer solution will not form the claimed granulate but provide new particles of the solid dispersion, where WO 208 does not teach the claimed process, where drying is carried out at a slower rate said to form the desired amorphous ENZ in polymer precipitate, not suggested or taught by WO 208.
In response, with regard to the Applicant’s statements above about the spray drying process, there is no citation either background of the art references noting the unsuitability of the spray dryer said to be referenced in WO 208 and its unsuitability to spray solvent on to a substrate to form granule. Nor is there is any expert testimony via Declaration or otherwise, referenced by Applicant other than Attorney Argument. See MPEP 2145(I.).8
Applicant states with regard to the claims 10 and 20, the Examiner is in error as the claimed dissolution properties are not inherent to its inventive process. Applicant argues that Example 14 does not contain a granulate at all, let alone the claimed granulate, and there is no basis to assert inherency.
Applicant states WO 208 shows that dissolution varies, where Example 25 notes differing dissolution rates for Examples 16-22 per Figures 3 and 4, and not the claimed dissolution profiles. Applicant states WO 208 does not meet the claimed dissolution standards, referencing Example 25: Figs. 3-4 in contrast to the testing methods of claims 10 and 20.
In response, it is noted that Examples 1-5 of the specification note the invention’s tablets are prepared by the process as depicted in the Flowchart of Figure 1. The process of the flowchart of Figure 1. See pages 13-17. XRPD analysis was performed to show no conversion into any crystalline form of ENZ, where the claimed dissolution rate of claims 10 and 20 were reported. Note that the product claims from which claims 10 and 20 depend from are broader than those specific examples 1-5 formed specifically by the process spelled out in the flow chart of Figure 1. Amendment of the claims to limit the composition claims to those formed by the process of Figure 1 (i.e. inclusive of the process steps of claims 11-13) so to recite a product by process composition will overcome the pending rejections of record.
Conclusion and Correspondence
Claims 1-5, 8-10, 14, and 18-20 remain rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application is a CON of Application No. 17765934 that claims earliest foreign priority to EP 19201339.9 with a priority date of 10/03/2019.
2 See Pion webpage “What are BCS Class I drugs?” accessed Dec 7 2024, reproduced below.
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https://www.pion-inc.com/blog/what-are-bcs-class-ii-drugs#:~:text=BCS%20stands%20for%20Biopharmaceutics%20Classification,high%20permeability%20but%20low%20solubility.
3 See MPEP 2144.05 Obviousness of Similar and Overlapping Ranges, Amounts, and Proportions [R-01.2024]
OVERLAPPING, APPROACHING, AND SIMILAR RANGES, AMOUNTS, AND PROPORTIONS
ROUTINE OPTIMIZATION
4 See MPEP 2112.01 II.(COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES)
5 See MPEP 2144.05 Obviousness of Similar and Overlapping Ranges, Amounts, and Proportions [R-01.2024]
OVERLAPPING, APPROACHING, AND SIMILAR RANGES, AMOUNTS, AND PROPORTIONS
ROUTINE OPTIMIZATION
6 See MPEP 2144.05 Obviousness of Similar and Overlapping Ranges, Amounts, and Proportions [R-01.2024]
OVERLAPPING, APPROACHING, AND SIMILAR RANGES, AMOUNTS, AND PROPORTIONS
ROUTINE OPTIMIZATION
7 See MPEP 2112.01 II.(COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES)
8 See MPEP 2145. I.ARGUMENT DOES NOT REPLACE EVIDENCE WHERE EVIDENCE IS NECESSARY
Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (“An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.”). See MPEP § 716.01(c) for examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration.
Prosecution Insights