Ex parte Shlieout, Appeal 2020-005326

• Court: United States Patent and Trademark Office. United States Patent and Trademark Office, Patent Trial and Appeal Board
• Writing for the Court: TOWNSEND, Administrative Patent Judge
• Parties: Ex parte GEORGE SHLIEOUT, CLAUS-JUERGEN KOELLN, FRITHJOF SCZESNY, JENS ONKEN, and GUIDO RUESING Technology Center 1600
• Decision Date: 02 April 2021
• Docket Number: 704,Application 11/464,Appeal 2020-005326

Ex parte GEORGE SHLIEOUT, CLAUS-JUERGEN KOELLN, FRITHJOF SCZESNY, JENS ONKEN, and GUIDO RUESING Technology Center 1600

Appeal 2020-005326

Application 11/464, 704

United States Patent and Trademark Office, Patent Trial and Appeal Board

April 2, 2021

FILING DATE: 08/15/2006

Before DONALD E. ADAMS, RYAN H. FLAX, and RACHEL H. TOWNSEND, Administrative Patent Judges.

DECISION ON APPEAL

TOWNSEND, Administrative Patent Judge

Pursuant to 35 U.S.C. § 134(a), Appellant^[1] appeals from the Examiner's decision to reject claims 77-82 and 84-15 directed to processes for the manufacture of pancreatin micropellet cores as being obvious. Oral argument was heard on March 23, 2021. We have jurisdiction under 35 U.S.C. §6(b).

We affirm. Our affirmance also includes new grounds of rejection.

STATEMENT OF THE CASE

"Pancreatin is a mixture of different physiologically active endogenous ingredients which are derived from mammalian pancreas glands and comprised of several different digestive enzymes such as lipases, amylases and proteases." (Spec. 3:9-11.) "Pancreatin for pharmaceutical use is typically of bovine or porcine origin with porcine pancreatin being preferred." (Id. at 3:14-15.)

"Pancreatin microspheres are the treatment of choice for diseases or disorders caused by digestive enzyme deficiency in mammals such as humans." (Id. at 1:13-14.) "This is due to the fact that high-performance pancreatin microsphere products. .. provide a therapeutically effective load of active enzymes while at the same time providing properly sized microspheres capable of targeting the optimal location in the digestive tract where digestive enzyme activity will be needed, in particular the upper intestine." (Id. at 1:14-18.)

According to Appellant's Specification it "has previously been understood" with respect to "manufacturing pancreatin micropellet products by extrusion and subsequent spheronisation of the extrudates" that "synthetic oils like paraffins, e.g. liquid paraffins (mineral oils)[, ] . .. [were] a necessary excipient." (Id. at 1:27-30.) Appellant's invention is directed to pancreatic micropellets that are enteric coated and are substantially free of synthetic oils. (Id. at 1:8-11, 2:18-20.)

Claims 77, 82, 112, and 136, reproduced below, are illustrative of the claimed subject matter:

77. A pharmaceutical composition comprising

(a) a pancreatin core, wherein the core consists of

(i) 70% to 90% pancreatin; and

(ii) 10% to 30% of at least one pharmaceutical acceptable binding agent, wherein the percentages of components are weight to weight of the core; and

(b) an enteric coating on the core

wherein the pancreatin core and the enteric coating are substantially free of synthetic oils, and wherein at least 55% of lipase activity in the composition is released within 30 minutes in a buffer solution at pH 6 as measured according to United States Pharmacopoeia

82. A delayed-release oral pharmaceutical composition comprising

(a) pancreatin micropellet cores comprising

(i) pancreatin; and

(ii) at least one pharmaceutically acceptable binding agent,

wherein the cores are substantially free of synthetic oils; and

(b) an enteric coating on the cores;

wherein the enteric coating is substantially free of monomeric phthalic acid esters;

wherein the composition has a relative gastric acid resistance of 75% or more following incubation for 2 hours in a phosphate buffer solution at pH 5; and

wherein at least 65% of lipase activity in the enteric coated pancreatin micropellets is released in 30 minutes in a phosphate buffer solution at pH 6.0 at 37°C, in a dissolution apparatus, using a paddle speed of 50 rpm, following 2 hours incubation in a gastric juice without enzymes at37°C, in a dissolution apparatus, using a speed of 100 rpm.

112. A delay ed-release oral pharmaceutical composition comprising:

(a) pancreatin micropellet cores comprising

(i) one active pharmaceutical ingredient consisting essentially of pancreatin and

(ii) at least one pharmaceutically acceptable binding agent,

wherein the cores contain no more than a pharmaceutically acceptable trace amount of synthetic oils; and

(b) an enteric coating on the cores;

wherein the composition has a relative gastric acid resistance of 75% or more following incubation for 2 hours in a phosphate buffer solution at pH 5; and

wherein at least 65% of lipase activity in the enteric coated pancreatin micropellets is released in 30 minutes in a phosphate buffer solution at pH 6.0 at 37°C, in a dissolution apparatus, using a paddle speed of 50 rpm, following 2 hours incubation in a gastric juice without enzymes at 37°C, in a dissolution apparatus, using a speed of 100 rpm.

136. A delayed-release oral pharmaceutical composition comprising:

(a) pancreatin micropellet cores consisting essentially of pancreatin and one or more suitable pharmaceutically acceptable excipients, wherein at least one excipient is a pharmaceutically acceptable binding agent; and

(b) an enteric coating on the cores;

wherein the composition has a relative gastric acid resistance of 75% or more following incubation for 2 hours in a phosphate buffer solution at pH 5; and

wherein at least 65% of lipase activity in the enteric coated pancreatin micropellets is released in 30 minutes in a phosphate buffer solution at pH 6.0 at 37°C, in a dissolution apparatus, using a paddle speed of 50 rpm, following 2 hours incubation in a gastric juice without enzymes at 37°C, in a dissolution apparatus, using a speed of 100 rpm.

(Appeal Br. 36- 45 (V. Claims Appendix (emphasis added).)

REFERENCES

The prior art relied upon by the Examiner is:

Name	Reference	Date
Sander-Struckmeier	US 7122357 B2	Oct. 17, 2006
Maio	US 2004/0101562 A1	May 27, 2004

REJECTIONS

We review the Examiner's rejection of claims 77-82 and 84-159 under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Sander-Struckmeier and Maio.

We however also institute the following new grounds of rejection, discussed in detail below:

Claims 77-82 and 84-159 under 35 U.S.C. § 102(b) as being anticipated by Maio.

Claims 77-82 and 84-135 as being indefinite under 35 U.S.C. § 112, second paragraph.

OPINION

I. Obviousness

The Examiner finds that Sander-Struckmeier teaches forming microsphere cores of pancreatin and polyethylene glycol with propan-2-ol. (Final Action 8.) The Examiner further finds that "the mixture is extruded and rounded using liquid paraffin and propan-2-ol prior to drying" and that if any of the liquid paraffin, which was added after formation of the core, remains, it would be about 2% or less of the core material, assuming complete evaporation of the alcohol. (Id. at 8, 9.) The Examiner concludes that the 2% or less of the liquid paraffin that might remain in the core "qualifies as being a 'trace' amount or wherein the core is 'substantially free' of said oil." (Id. at 9.) In addition, the Examiner concludes that because "Applicant has not provided what the basic and novel characteristics of 'consisting essentially of exactly are . .. then oils in trace amounts are permitted to be present in the final composition of claim 136 even though synthetic oils are not, per se, a pharmaceutical acceptable excipient as defined by the Applicant in the specification at (pg 5, lns 18-19)." (Id.)

The Examiner also finds that the core is taught to be enteric coated. (Id. at 8.) The Examiner acknowledges that Sander-Struckmeier does not explicitly teach the lipase activity and its release time, but concludes that because the "prior art teaches the identical chemical structure" claimed, the properties claimed "are necessarily present. In re Spada, 911 F.2d 705, 709 (Fed Cir. 1990)." (Id. at 9.)

The Examiner recognizes that "Sander-Struckmeier does not teach an enteric coating that is substantially free of monomeric phthalic acid esters" (Id. at 10). This is not a limitation of independent claims 77, 112, and 136. However, it is a limitation required by independent claim 82, and dependent claims 109 (depending from independent claim 77), 113 (depending from independent claim 112), and 137 (depending from independent claim 136)).

The Examiner finds that replacing the enteric coating of Sander-Struckmeier with one that is substantially free of monomeric phthalic acid esters would have been obvious in light of the teachings of Maio. (Id.) The Examiner states that "Maio teaches pancreatin micropellets consisting of pancreatin and PEG4000 that are formed into spherical granules and coated with an enteric coating [0052-0053]." (Id.) The Examiner notes that the enteric coating taught "comprises HP-55 polymer, triethylcitrate, and talc and is completely free of monomeric phthalic acid esters." (Id.) The Examiner concludes that substituting the coating of Maio for the coating of Sander-Struckmeier would have been obvious because, "[g]enerally, it is prima facie obvious to substitute one equivalent component or process for another, each of which is taught by the prior art to be useful for the same purpose (see MPEP 2144.06)." (Id.)

Appellant disagrees with the Examiner's position that about 2% liquid paraffin in the Sander-Struckmeier cores complies with the requirements of the independent claims, namely that the core be "substantially free of synthetic oils" or that it "contain[s] no more than a pharmaceutically acceptable trace amount of synthetic oils," or "consist[] essentially of pancreatin and one or more suitable pharmaceutically acceptable excipients." (Appeal Br. 10-12.) According to Appellant these phrases should be construed as requiring pancreatin core compositions "containing approximately 0% synthetic oils." (Appeal Br. 23-25.)

Appellant...