UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS P.O. Box 1450
Alexandria, Virginia 22313-1450 www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/998,180 03/24/2011 Fr¿d¿ric Gerber 247004-205 9655
20999 7590 05/05/2025
HAUG PARTNERS LLP
745 FIFTH AVENUE - 10th FLOOR
NEW YORK, NY 10151
EXAMINER
CHANNAVAJJALA, LAKSHMI SARADA
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
05/05/2025 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es):
docket@haugpartners.com
PTOL-90A (Rev. 04/07)
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UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE PATENT TRIAL AND APPEAL BOARD
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Ex parte FRÉDÉRIC GERBER and BURKHARD SCHLUETERMANN ——————
Appeal 2024-000958
Application 12/998,180
Technology Center 1600
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Before DONALD E. ADAMS, GEORGIANNA W. BRADEN, and RACHEL H. TOWNSEND, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1appeals from the Examiner's decision to reject claims directed to a tablet comprising particles. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
Appellant's Specification describes pharmaceutical tablets in which the active ingredient is provided by subunits/particles of the active ingredient, for example "pellets or spherical particles." (Spec. 1.) The
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Specification explains that "[t]hese typically have either a layer-like structure or a matrix structure," which can be coated with a film. (Id.) The Specification notes that these "systems disintegrate into their subunits, which in each case can exhibit a desired controlled release behavior." (Id. at 2.) The Specification states that "compression of multiparticulate systems, especially of coated multiparticulate systems, however, is not simple." (Id. at 3.) The Specification further states:
Important factors that play a role in the production of a qualitatively high-quality multiparticulate administration form are, in addition to a) the selection of suitable pharmaceutical excipients, and b) the choice of suitable, well-controlled production methods, also c) the structure of a tablet.
(Id.)
Appellant's claimed invention is directed at a multiparticulate tablet formulation that has an inner phase of granulated active ingredient and an outer phase, "understood functionally, not spatially," that contains disintegrants, lubricants, flow-regulating agents, fillers and/or binders. (Id. at 4, 11-12.)
CLAIMED SUBJECT MATTER
Claims 1-3, 5-7, and 9-24 are before us on appeal. (See Final Action 1.) Claim 1, reproduced below, illustrates the claimed subject matter:
1. A tablet for oral administration, comprising:
an inner phase comprising:
a plurality of first particles, each first particle containing a first active ingredient, and having a coating and/ or releasing the active ingredient in a modified manner; and spherical particles which contain a second active ingredient that is the same or different from the first active ingredient, and which have a
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density of less than 0.8 g/ml and an absolute porosity in a range of from 0.5 to 30 percent; and an outer phase comprising one or more excipients present in non-granulated form before tableting, the one or more excipients selected from the group consisting of disintegrants, lubricants, flow regulators, fillers, and binders; wherein the plurality of first particles and the spherical particles together make up at least 75 percent of the total weight of the tablet; and
wherein the weight of the outer phase makes up not more than 25 percent of the total weight of the tablet.
REFERENCES
The Examiner relies on the following references to reject the claims:
Name Reference Date
Singh US 7,115,281 B2 Oct. 3, 2006 Parikh US 8,153,159 B2 Apr. 10, 2012 B. Johansson
and
G. Alderborn
The effect of shape and porosity on the compression behaviour and tablet forming ability of granular materials formed from microcrystalline cellulose, 52(3) Eur. J Pharm. & Biopharm. 347-57
2001
REJECTION
The following rejection by the Examiner is before us on review:
Claims 1-3, 5-7, and 9-24 are rejected under pre-AIA 35 U.S.C. § 103 as being unpatentable over Singh, Parikh, and Johansson. (Final Action 2.)
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DISCUSSION
Appellant does not argue the claims separately. Where "claims are not separately argued, they all stand or fall together." In re Kaslow, 707 F.2d 1366, 1376 (Fed. Cir. 1983); 37 C.F.R. § 41.37(c)(1)(iv). Therefore, we focus on the Examiner's rejection as it relates to independent claim 1. The Examiner found that Singh teaches a tablet dosage form of the active ingredient modafinil for oral administration in which the dosage form includes modafinil in different particle sizes. (Final Action 3-4.) The Examiner found, in particular, that the dosage form includes an inner phase, i.e., intragranular phase, where the inner phase includes a mixture of modafinil particles having a diameter greater than 220 μm (coarse particles) present from 7-25% by weight, and modafinil particles having a diameter less than 220 μm (fine particles) present from 93-75% by weight, as well as including excipients such as lactose, starch, croscarmellose sodium, and povidone. (Final Action 3 (citing Singh 1:37-49 and Table 1).) The Examiner further found that Singh teaches an outer phase, i.e., the extragranular phase, which includes croscarmellose sodium, talc, colloidal silicon dioxide, and magnesium stearate. (Id. (citing Singh 1:37-49,Table 1, 5:43-46, and 6:6-14).) The Examiner also found that Singh exemplifies a composition of the foregoing, where the outer phase included 22.5 mg compared with the 477 mg of the inner phase of the tablet, making up 4.7% of the particles of the tablet.
The Examiner further found that Singh teaches the ingredients of the tablet can be modified in order to select a desired dissolution profile. (Id at 4 (citing Singh 7:13-27).) The Examiner determined that such modification
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provides for the claim limitation "releasing the active ingredient in a modified manner." (Id.)
The Examiner recognized that the claim provides for "releasing the active ingredient in a modified manner" or a coating as alternatives, but, nevertheless addressed the obviousness of a composition that includes first particles having a coating. The Examiner addressed this limitation turning to Parikh. The Examiner also turned to Parikh to address the claim requirement of spherical particles. (See Final Action 4-6.)
The Examiner found that Parikh, like Singh, teaches pharmaceutical compositions of modafinil that may be in a tablet dosage form, and that such forms can be prepared in a way to have modified release (such as enteric release) or pulsatile release. (Id. at 4 (citing Parikh abstr., 5:40-62, 10:25- 30), see also id. at 5(citing Parikh Table 1).) Regarding such preparation, the Examiner found that Parikh teaches that the active core of modafinil in the dosage form is prepared by combining modafinil, binders such as PVP, and a rate controlling polymer such as high viscosity HPMC, a well as other excipients, which are blended to form spherical particles and then the core is coated with one or more coatings (Id. at 4-5 (citing Parikh 5:64-6:11, 6:40- 50, 6:54-63).) The Examiner further found that Parikh provides specific examples of various extended release formulations in Table 1. (Id.) The Examiner concluded that it would have been obvious to one having ordinary skill in the art to have modified the particles of Singh as spherical particles and to have coated them in view of Parikh's teachings in order to provide the release profile described by Parikh, such as enteric release, pulsatile release, or delayed release. (Final Action 5.)
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Regarding the inclusion of particles that are spherical and have the claimed density and absolute porosity claimed, the Examiner found such would have been obvious from the teachings of Johannson, which "suggests the importance of porosity, density, as well as the sphericity (shape) of the granules or pellets in obtaining the compression strength of the tablets (last para of page 12 & Fig 6 a-c)." (Final Action 6-8.) In particular, the Examiner found that Johansson teaches that in compression of pharmaceutical granules that occurs during tableting (1) fragmentation of granules into smaller agglomerates occurs, (2) deformation of the shape of individual granules occurs, and (3) reduction in granule porosity also occurs. (Final Action 6-7 (citing Johansson Introduction).) The Examiner further found that Johansson teaches that the original porosity of the pellets is critical for the evolution of tablet structure and strength during compression. (Id. at 7.) The Examiner stated in particular that
Fig. 5a-c [of Johansson] shows the degree of compression of granules and pellets as a function of porosity, shape coefficient and density of the granules, where fig 5a shows that at low porosity required a lower degree of compression, increased irregular shapes increased the degree of compression (5b) and increased density reduced the compression (fig. 5c) and that the bulk density of the granular material before compression controlled the degree of compression (page 11, last para). (Id. (citing Johansson 11).) The Examiner further found that the ranges of porosity and bulk density in Figure 5 of Johansson includes the claimed ranges. (Id.) The Examiner concluded that it would have been obvious from the teachings of Johansson to prepare a spherical particle that has an optimum density and porosity in the claimed range to achieve the desired tensile strength of the tablet. (Id. at 8.)
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We agree with the Examiner's findings and conclusion of obviousness. We address Appellant's arguments set forth in the Appeal Brief below. We note that Appellant raises several arguments in the Reply Brief that are entirely new and different from those articulated in the Appeal Brief. Appellant has not demonstrated any specific Examiner findings presented for the first time in the Answer necessitating these new arguments in rebuttal in the Reply Brief. Nor do we find any substantial differences in the Examiner's initial findings and the Examiner's findings stated in the Answer that would warrant the new arguments presented in the Reply Brief for the first time. "[T]he reply brief [is not] an opportunity to make arguments that could have been made in the principal brief on appeal to rebut the Examiner's rejections, but were not." Ex parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative). Appellant's arguments advanced in such a manner in the Reply Brief have not afforded the Examiner an opportunity to respond to these new arguments. As stated in Ex parte Borden, consideration by the Board of new arguments presented for the first time in the Reply Brief that could have been presented earlier would "vitiate the force of the requirement in Board Rule 37(c)(1)(vii) that '[a]ny arguments or authorities not included in the brief . . . will be refused consideration by the Board, unless good cause is shown."' Id. We, therefore, base our decision only on those arguments timely raised in the opening Appeal brief. In the Appeal Brief, Appellant argues that because Singh addressed different problems not related to "multiparticulate forms," which is what Appellant's claimed invention was directed at solving, "persons skilled in the art would not look to Singh as a solution to [those] problems." (Appeal Br. 7-8.) We do not find Appellant's argument persuasive because "the
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patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure." Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir. 2002). Moreover, prima facie obviousness does not require prior art references to recognize or even suggest the problem that applicant attempted to solve. See In re Kemps,
97 F.3d 1427, 1430 (Fed. Cir. 1996); In re Beattie, 974 F.2d 1309, 1312 (Fed. Cir. 1992); see also KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 419 (2007) ("In determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. What matters is the objective reach of the claim. If the claim extends to what is obvious, it is invalid under § 103."). Appellant's argument does not explain or provide evidence demonstrating how the structure of the formulation described by Singh does not meet the claim limitations identified by the Examiner.
Appellant further argues that Singh does not teach or suggest
"modify[ing] the modafinil particles so as to provide particles having a coating and/or releasing the active ingredient in a modified manner, and there is no suggestion to incorporate spherical particles meeting certain density and porosity requirements." (Appeal Br. 9.) This argument is also unavailing for several reason. We address the claim requirement that "the plurality of first particles . . . and having a coating and/or releasing the active ingredient in a modified manner" first.
As the Examiner explained, the use of "and/or" connecting coating with the releasing claim element means that the claim does not require a coating over the particles. (Ans. 11.) Moreover, as the Examiner also
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explained (Ans. 5, 10), Singh teaches a mixture of coarse and fine particles of modafinil in the inner phase of the tablet composition and states:
[t]he dissolution data of Examples 1-3 demonstrates an ability and method to make a dosage form of modafinil in which the dissolution of the modafinil particles can be modified by varying the above ingredients to select a desired dissolution profile in which a great majority of the modafinil particles are released within 60-90 minutes. For example, if there is a desire to provide a large initial release of the modafinil, e.g., within fifteen minutes, the formulations of Examples 1 and 2 are most suitable. If there is a desire to provide less of an initial release of the modafinil, the formulation of Example 3 is most suitable. As can be seen from the data in Table 2, the dissolution profile can be modified by varying the relative amounts of coarse and fine modafinil particles, as well as by varying the size distribution of the fine particles
(Singh 7:13-27.) Table 2 of Singh demonstrates that modifying the size distribution of the fine particles can change the percent release over time of modafinil (compare Example 1 with Example 2 in Tables 1 and Table 2), just as changing the distribution amount of coarse particles as compared to fine particles can change the percent release over time of modafinil (compare Example 2 with Example 3 in Tables 1 and 2). As the Examiner noted, Claim 1 "does not recite any particular release rate nor specify" a particular modification. (Ans 11.) Appellant's argument does not persuasively establish how the limitation that the plurality of first particles so described in Singh does not satisfy the requirement of "releasing the active ingredient in a modified manner."
Appellant argues, in addition, that Singh's formulation that incudes modafinil particles of different sizes of pure active ingredient, which are combined with excipients and then subjected to wet granulation, leads "to one type of granule particles" which are subjected to conventional tableting
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to arrive at a monolithic tablet, and not "a multiple-unit pharmaceutical form." (Appeal Br. 9-10.) We do not find this argument persuasive. Appellant's argument is not altogether clear as it relates to why the Singh dosage form the Examiner relied in the rejection does not meet the claim requirements. We presume Appellant's argument is that Singh's blend of differently sized particles having a particular distribution of coarse and fine particles and including excipients when undergoing wet granulation leads to granules of particles of "one type" is that the "one type" of granule no longer has modafinil particles of different sizes in the inner phase. Appellant does not provide evidence, however, establishing that premise. "Attorneys' argument is no substitute for evidence." Johnston v. IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989). As the Examiner stated: "Singh clearly suggests maintaining different particles containing different sizes, admittedly, for providing the desired dissolution profile, and hence meet instant multiparticulate inner phase." (Ans. 10; see also id. at 12.) Moreover, as the Examiner further noted claim 1 does "not require multiple types of granules, and instead recite[s] an inner phase comprising first and second particles, which is met by the different particle sizes of modafinil." (Id. at
12.)
Appellant also argues that "it is incorrect to rely on Singh's Table 1 . . . in calculating the proportions of inner and outer phases because Singh does not have an inner phase comprising the claimed plurality of first particles as claimed with a coating and or releasing the active ingredient in a modified manner and spherical particles as claimed. (Appeal Br. 10.) We do not find this argument persuasive for the reasons identified by the Examiner in the Answer (Ans. 12) and as discussed above. In particular, Singh teaches
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a tablet with an inner phase that includes a distribution of coarse particles and a distribution of fine particles, i.e., two different types of particles that provide for modified release, as well as having an outer phase. As the Examiner noted, the Appellant has "not provided any reasoning as to why the inner and outer phases of the composition of Singh does not meet the claimed percentages." (Ans. 12.) Nor has the Appellant explained with supporting factual evidence why it would not have been obvious to have modified Singh to include spherical particles as taught by Parikh and modified by Johannson, and maintain the percentages that Singh discloses for the inner and outer phase. The Examiner found, and we agree, with respect to the combination of Singh with Parikh, that "one of an ordinary skill in the art would have been able to maintain low % outer phase (of Singh-Table I) to the exemplified 22.5% (table 1) or further reduce to even lower amounts so as to be able to provide a desired rate of release of the active agent." (Final Action 6.) The Examiner found further in this regard:
it would have been obvious for one of an ordinary skill in the art to optimize the amount of active agent in different particles of Modafinil, further choose the desired amount of active agent in the inner phase, as well as reduce the amount of excipients (in the outer phase) while increasing the active agents in the inner particles with an expectation to provide the desired dissolution as well as release rate of the active agent from the particles of the tablet (of Singh). In this regard, Parikh teaches controlled or modified released of modafinil (col. 4, l 30-67; col. 6, l 13-55). Parikh also teaches multi-coated drug
containing particles for immediate release or time-controlled release (col. 8, l 16-27).
(Id.)
Appellant further argues that "there is no suggestion [in Singh] to incorporate spherical particles meeting certain density and porosity
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requirements." (Appeal Br. 9.) This argument is not persuasive, because as the Examiner noted regarding spherical particles, the rejection relies on the teachings of Parikh. (Ans. 11.) Moreover, as to the density and porosity requirements of spherical particles to be used in a tablet dosage form, the Examiner relied on Johannson. As the Examiner further explained:
Singh reference teaches preparing tablets comprising modafinil microparticles having improved flow properties and further preparing compressed tablets, and further Parikh suggests preparing spherical particles of modafinil with a modified release coating. Johansson teaches the effect of shape and porosity on the compression behavior and tablet forming ability of granular materials. . . . Johansson also shows that the degree of compression is a function of intragranular porosity and density of pellets and granules, which includes the claimed porosity and density the particles. Accordingly, one of an ordinary skill in the art preparing modafinil particles of Singh (modified by Parikh) would have been motivated to look to the relevant teachings of Johansson in tableting art and choose the modafinil particles with claimed density of less than 0.8 g/ml and porosity of 0.5 to 30 percent, with an expectation to provide optimum compression strength of the tablet.
(Ans. 14). "Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references. . . . [The reference] must be read, not in isolation, but for what it fairly teaches in combination with the prior art as a whole." In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Thus, for this reason, we also do not find persuasive Appellant's argument related to Johansson, i.e., that it "does not teach or suggest the claimed plurality of first particles having a coating and/ or releasing the active ingredient in a modified manner and spherical particles meeting certain density and porosity requirements." (Appeal Br. 12.)
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Appellant argues that Parikh does not supply the missing limitations from Singh (Appeal Br. 10), but we disagree with Appellant as to what is
"missing" in Singh. Singh is missing a teaching regarding including spherical particles, or coated particles as an alternative to simply having the property of "releasing the active ingredient in a modified manner." For the reasons set forth above, the Examiner has established it would have been obvious to include spherical particles in the Singh formulation from the teachings of Parikh. Parikh itself need not establish a multiparticulate tablet (Appeal Br. 10-11), as that is established by Singh.
Appellant argues that Singh "uses active ingredient particles of different sizes of modafinil in a formulation that is subjected to conventional wet granulation" and one of skill in the art "would not reasonably have considered preparing coated modafinil particles and then combin[e] them with excipients in a wet granulation process." (Id. at 12.) Appellant argues that "there is no reasonable way to combine the teachings of Singh and of Parikh, and the skilled person would not have been motivated to do so. Both documents suggest independent-indeed, incompatible-concepts to provide for a controlled release." (Id.) Here again, Appellant has provided no evidentiary support for the argument that a coated particle is incompatible with Singh's particulate formulation. Second, the Examiner's rejection relies on Singh for the plurality of first particles having the release requirements based on differential sizing and then Parikh for spherical particles that may or may not be coated. As discussed above, by use of the phrase "and/or" in claim 1, the first particles do not need to be coated. Furthermore, "[i]n determining whether obviousness is established by combining the teachings of the prior art, the test is what the combined
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teachings of the references would have suggested to those of ordinary skill in the art." In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal quotations omitted). As the Examiner noted, Singh and Parikh are analogous art. Parikh teaches coating was known in the art and could be done via wet granulation to provide for sustained release granules which may be compressed into a tablet. (See, e.g., Parikh, col. 20 (Example 7).) Moreover, as the Examiner noted, Parikh also teaches making coated spherical granules where the granules may be made via wet granulation and spheronizing the particles. (Ans. 13 (citing Parikh 6:40-50).) The Examiner explained that
"one of an ordinary skill in the art would have been motivated to modify the modafinil particles of different sizes (of Singh) so as to prepare spherical particles and further coat the particles with a release modifying polymer before further compressing to form oral tablets." (Id.) We find the evidence in the art supports this conclusion. The Examiner further explained that
"[o]ne of an ordinary skill in the art would have been motivated to do so with an expectation to achieve a desired release profile, and in this regard, Singh also desires providing modified dissolution patterns." (Id.) We find the evidence also supports this conclusion.
In light of the foregoing, we affirm the Examiner's rejection of claims 1-3, 5-7, and 9-24 under 35 U.S.C. §103 as being unpatentable over Sigh, Parikh, and Johannson.
DECISION SUMMARY
The following table summarizes our decision:
Claim(s) Rejected
35 U.S.C.
§ Reference(s)/ Basis Affirmed Reversed
1-3, 5-7, 9-24 103 Singh, Parikh, Johansson
1-3, 5-7, 9-
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TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R. § 1.136(a)(1)(iv).
AFFIRMED
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