Ex Parte Harel

Patent Trial and Appeal Board

Feb 1, 2017

11597826 (P.T.A.B. Feb. 1, 2017)

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.
11/597,826 08/23/2007 Mordechai Harel ABN-125US 1976
23122 7590 02/03/2017
RATNFRPRFSTTA
EXAMINER
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Please find below and/or attached an Office communication concerning this application or proceeding.
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MORDECHAI HAREL1
Appeal 2015-005846
Application 11/597,826
Technology Center 1600
Before DONALD E. ADAMS, MELANIE L. McCOLLUM, and TAWEN
CHANG, Administrative Patent Judges.
McCOLLUM, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a particle
that is suitable for oral administration. The Examiner has rejected the claims
as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
1 Appellant identifies the real party in interest as Advanced BioNutrition
Corp. (App. Br. 1).
Appeal 2015-005846
Application 11/597,826
STATEMENT OF THE CASE
Claims 1, 4, 5, 10-16, 18, 20-22, 24, 25, 27-31, 38, 45, 48-56, and
102 are on appeal (App. Br. I).2 Claims 1 and 24 are representative and read
as follows:
1. A particle suitable for oral administration of a bioactive agent to an
animal, the particle comprising a substantially indigestible and crosslinked
polymer matrix having suspended and entrapped therein an admixture
comprising a solid lipid/bioactive agent particle comprising (i) the bioactive
agent and (ii) at least one lipid that is solid at room temperature and is
dissoluble in the animal, wherein the substantially indigestible and
crosslinked polymer matrix of the particle comprises a mixture of high
amylose starch, lecithin and alginic acid, wherein the ratio of lecithin to
starch is 1 part lecithin to 3 to 5 parts starch, wherein the lipid comprises an
oil selected from the group consisting of vegetable oils, fish oils, algal oils,
microbial oils, and combinations of these.
24. The particle of claim 1, wherein the bioactive agent comprises a
microorganism.
Claims 1, 4, 5, 10-16, 18, 20-22, 24, 25, 27-31, 38, 45, 48-56, and
102 stand rejected under 35 U.S.C. § 103(a) as obvious over Akiyama et al.
(US 5,731,006, Mar. 24, 1998) in view of Tester et al. (US 6,649,191 Bl,
Nov. 18, 2003), Chapura et al. (US 4,786,502, Nov. 22, 1988), and
Vandenberg (US 2003/0118547 Al, June 26, 2003) (Ans. 2).
The Examiner relies on Akiyama for disclosing “gastrointestinal
matrix compositions comprising a viscogenic agent dispersed alongside a
matrix particle containing an active agent and a lipid” {id. at 3). The
Examiner finds that Akiyama discloses that the “viscogenic agent can be a
2 Claims 19, 23, 26, 69—74, and 78 are also pending but have been
withdrawn from consideration (Final Act. 1).
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Application 11/597,826
cellulose ether (which is a polysaccharide containing polymer) or a
naturally-occurring mucous substance such as alginate” (id.). The Examiner
also finds that Akiyama discloses “that the viscogenic agent can be
contained inside the . . . matrix or used as a coating” (id.). In addition, the
Examiner finds that Akiyama discloses “that the polymeric matrix contains
the solid lipid and said solid lipid contains the active agent wherein the solid
lipid/agent mix is in the form of a particle” (id.). The Examiner also finds
that Akiyama discloses that the “lipid can be selected from oil and lecithin”
(id.). In addition, the Examiner finds that Akiyama discloses “that said
matrix can comprise other polymers and excipients including com starch (an
amylose starch)” (id.). Therefore, the Examiner finds that Akiyama
“reasonably disclose[s] at least a particle for sustained dmg release in the
gastrointestinal tract, said particle comprising a polymer matrix, wherein
said polymer matrix comprises lipids, an active ingredient, an amylose
starch, alginate” (id. at 4).
The Examiner relies on Tester for disclosing “a cation cross-linked
polysaccharide and polymer matrix that is indigestible in the stomach but
digestible in the lower gastrointestinal tract” (id.). The Examiner finds that
Tester discloses “that these cation cross-linked starch-type polymer matrices
have superior taste-masking properties and can mask the taste of active
agents” (id.). The Examiner also relies on Tester for disclosing “that the
cation cross-linked starch-type polymer matrix can comprise high amylose
starch and alginic acid . . . , can support biological agents in the matrix . . . ,
and can be formulated as granules (i.e. particles), capsules, etc.” (id.). The
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Application 11/597,826
Examiner finds that Tester discloses “that high amylose starch appear[s] to
retard drug release in water, acid” (id.).
The Examiner relies on Chapura for disclosing “a polymer matrix in a
particle comprising from about 10-15% lipid, 10-50% dispersant particulate
material, 0.1-3% emulsifier, and an active ingredient” (id. at 5). The
Examiner finds that Chapura discloses “that the dispersant material can be
com starch (an amylose starch) and the emulsifier material can be fats, i.e.
fatty acids (id.). The Examiner concludes that “the scope of Chapura et al.
would include at least a ratio of 1:3-5 (emulsifier:starch)” (id.).
The Examiner relies on Vandenberg for disclosing “a composition for
intestinal delivery comprising a therapeutic agent, wherein said composition
can be orally administered,” and for disclosing that “fish oil is a lipid that
can be incorporated into said composition and facilitates the absorption of
the therapeutic agent across the mucosal tissues in the intestinal mucosa”
(id.).
The Examiner concludes:
It would have been obvious to one of ordinary skill in the art at
the time that the invention was made to modify the teachings of
Akiyama et al. by applying the teachings of Tester et al., Chapura
et al., and Vandenberg to arrive at a particle [according to
representative claim 1], . . . Specifically, the motivation to
incorporate the teachings/suggestions of a cation cross-linked
starch-type polymer matrix comprising high amylose starch and
alginic acid of Tester ... for the polymer matrix of Akiyama et
al. would be to allow for sustained release of active ingredients
(i.e. drugs) in the gastrointestinal tract (which is also the purpose
of Akiyama et al.’s particles), while masking the taste of the
drugs.
(Id. at 5—6.)
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With regard to claim 24, the Examiner additionally finds that
Vandenberg discloses “that the composition for gastrointestinal delivery can
include an attenuated microorganism which helps to induce mucosal
immunity in the host animal against mucosal infectious diseases” {id. at 7).
The Examiner concludes that it would have been obvious “to further modify
the teachings of Akiyama et al. by incorporating an attenuated
microorganism . . . into said composition ... to induce mucosal immunity in
the host against mucosal infectious diseases” {id. at 8).
FINDINGS OF FACT
We include the following findings of fact (FF) for emphasis and for
ease of reference:
1. Akiyama discloses “a gastrointestinal mucosa-adherent matrix
which is solid at ambient temperature, and which contains a viscogenic
agent as dispersed at least in the neighborhood of the surface layer of a
matrix particle containing a polyglycerol fatty acid ester and/or a lipid and
an active ingredient” (Akiyama, col. 2,11. 3 5—41).
2. Akiyama also discloses that the “gastrointestinal mucosa-
adherent matrix which is solid at ambient temperature includes a matrix in
which each matrix particle containing a polyglycerol fatty acid ester and/or a
lipid and an active ingredient has a coating layer comprising or containing
the viscogenic agent” {id. at col. 2,11. 41—46).
3. In addition, Akiyama discloses that the “coating composition
may further contain at least one member selected from the group consisting
of polyglycerol fatty acid esters, lipids, enteric polymers and water-insoluble
polymers” {id. at col. 2,11. 50-55).
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4. As the viscogenic agent, Akiyama mentions naturally-occurring
mucous substances, such as alginate and waxy starch {id. at col. 3,1. 19, to
col. 4,1. 4).
5. Akiyama also discloses that “examples of the lipid include, for
example,. . . oils (e.g. castor oil, cottonseed oil, soybean oil, rapeseed oil,
beef tallow and other hardened oils). . . [and] phospholipids (e.g.
hydrogenated lecithin and the like)” {id. at col. 5,11. 36-49).
6. In addition, Akiyama discloses that “[t]here is no particular
limitation on the type of active ingredient” {id. at col. 5,11. 53—54).
7. Akiyama also discloses that “various additives which are
commonly used in the manufacture of solid pharmaceutical preparations,
particularly fine granules or granules, may be added to the particles” {id. at
col. 10,11. 4—7).
8. In particular, Akiyama discloses that the additives “include
various excipients such as . . . com starch . . . [and] binders such as starch”
{id. at col. 10,11. 8—13).
9. In addition, Akiyama discloses:
[I]nsofar as the viscogenic agent is allowed to exhibit its mucosal
adhesivity in the gastrointestinal tract, the matrix may, where
necessary, have an enteric or gastric coating or the like. For
example, when the matrix has an enteric coating layer which is
adapted to dissolve in the vicinity of the site of absorption, the
matrix will adhere to the site of absorption to function as a target-
oriented dmg delivery system.
{Id. at col. 13,11. 33—40.)
10. Tester discloses “[o]rally administrable compositions
comprising cation cross-linked polysaccharides,” the “compositions hav[ing]
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Application 11/597,826
the ability to mask the taste and delay the release of an active material
included therein” (Tester, Abstract).
11. Tester also discloses that the “cation cross-linked
polysaccharide is preferably selected from alginic acid and demethylated
pectin and the composition further comprises a digestible polymer,
preferably chosen from starch, starch derivatives, a-glucans, peptides and
polypeptides” (id.).
12. In addition, Tester discloses:
The addition of a starch-type polymer makes it possible to more
accurately target the site of release on an active material from the
compositions within the GI tract. For example, by employing a
polymer that is resistant to the acidic environment of the stomach
but is digested by the amylase enzymes of the ileum, it is possible
to effect drug release in the small intestine.
However, if the starch-type polymer is predominantly
digested by the microorganisms present in the colon, it is
possible to affect colonic release.
(Id. at col. 7,11. 12-21.)
13. Tester also discloses: “The starches used may contain between
0 and 100% of amylose .... The choice of starch may be influenced by the
nature of the desired release. . . . High amylose starches appear to retard
drug release in water, acid and a-amylase more effectively.” (Id. at col. 9,
11. 3-15.)
14. In addition, Tester discloses that its compositions may “be used
in the preparation of dosage forms that comprise bacteria as the active
material” (id. at col. 8,11. 8—10).
15. Vandenberg discloses “a method of immunization of a host
against mucosal microorganisms which comprises orally administering to
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the host an immunizing amount of microbial surface protein in the form of
killed whole microorganisms” (Vandenberg 144).
ANALYSIS
The Examiner concludes that Akiyama, Tester, Chapura, and
Vandenberg suggest the particles of claims 1 and 24 for the reasons set forth
in the Final Rejection and the Examiner’s Answer, which are summarized
above. We conclude that Appellant has not adequately shown why the
Examiner’s position is in error.
In particular, Appellant argues:
[Cjrosslinking Akiyama’s particles would entrap the viscogenic
agent. As long as the crosslinking were intact, it would prevent
the viscogenic agent from bleeding out onto the particle surface,
thereby preventing contact of the viscogenic agent with the
internal tissues of the gastrointestinal tract. The crosslinked
particles would not be sticky and they would move more rapidly
through the gastrointestinal tract, thus defeating the stated
purpose of Akiyama’s invention.
(App. Br. 5.) We are not persuaded.
As noted by the Examiner (Ans. 9), Akiyama discloses:
[Ijnsofar as the viscogenic agent is allowed to exhibit its mucosal
adhesivity in the gastrointestinal tract, the matrix may, where
necessary, have an enteric or gastric coating or the like. For
example, when the matrix has an enteric coating layer which is
adapted to dissolve in the vicinity of the site of absorption, the
matrix will adhere to the site of absorption to function as a target-
oriented drug delivery system.
(FF 9.) Thus, Akiyama’s disclosure is not inconsistent with, and is in fact
expressly open to, the delayed delivery of an active agent. Appellant’s
arguments do not persuade us that the corresponding delayed release of the
viscogenic agent would negatively impact its ability to achieve its intended
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purpose. In particular, Appellant has provided insufficient evidence that
there would have been a need to release the viscogenic agent before the
particle reached its target site, particularly in view of the disclosure of “an
enteric or gastric coating” (id.).
Appellant also argues that there would have been no reason to use
high amylose starch in Akiyama’s particles (App. Br. 6). In particular,
Appellant argues that “[njeither Akiyama nor Tester indicates that high
amylose starch would be suitable as a viscogenic agent, so it would not have
been obvious to include it for that purpose” (id.). We are not persuaded.
We note that Akiyama discloses including a waxy starch as a
viscogenic agent (FF 4). However, the Examiner is not arguing that it would
have been obvious to replace this waxy starch with a high amylose starch.
Instead, the Examiner finds that Akiyama discloses “that said matrix can
comprise other polymers and excipients including com starch (an amylose
starch)” (Ans. 3 (citing Akiyama, col. 10,11. 4—16 (FF 7—8))). In addition,
the Examiner finds that Tester discloses that high amylose starch appears to
retard dmg release in water and acid (Ans. 4 (citing Tester, col. 9,11. 14—15
(FF 13))). Thus, the Examiner concludes that it would have been obvious to
include high amylose starch in Akiyama’s particles “to allow for sustained
release of active ingredients (i.e. dmgs) in the gastrointestinal tract”
(Ans. 6). We conclude that Appellant has not adequately explained why the
Examiner’s reasoning is incorrect.
Appellant argues: “High amylose starch delays dmg release until
after the dmg has passed out of the stomach, an acidic environment.
Akiyama would not want that.” (App. Br. 7.) However, for the reasons
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discussed above, Akiyama’s disclosure is not inconsistent with, and is in fact
expressly open to, the delayed delivery of an active agent after the drug has
passed out of the stomach (FF 9).
Appellant also argues that using high amylose starch would further
delay drug release “because high amylose starch is resistant to the amylase
found in the ileum” (App. Br. 7). However, Appellant has not adequately
explained why this would not have been desired in some circumstances. As
noted by Appellant {id.), Tester discloses that, “if the starch-type polymer is
predominantly digested by the microorganisms present in the colon, it is
possible to affect colonic release” (FF 12). This teaching presumes that
colonic release is sometimes desired. We acknowledge Appellant’s position
that absorption may be lower there (Reply Br. 5).3 However, we do not
agree that this demonstrates that it is never desired.
In addition, Appellant argues that, “[wjhile Akiyama may sometimes
target drug delivery in the intestine, the skilled person would not have used
high amylose starch to do it, because . . . Akiyama handles that task by
coating with enteric polymers” (Reply Br. 4). However, Akiyama discloses
that “the matrix may . . . have an enteric or gastric coating or the like” (FF 9
(emphasis added)). Thus, Akiyama is clearly not limited to the use of
enteric coatings to target drug delivery. In addition, Tester discloses a
composition for targeting drug delivery (FF 12).
Appellant also argues that there is no reason to make Akiyama’s
particles substantially indigestible, which is defined “as relating to
3 “Reply Br.” refers to the Replacement Reply Brief filed May 18, 2015.
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digestibility in the stomach” (App. Br. 8). However, we are not persuaded
by this argument for the reasons discussed above.
With regard to claim 24, Appellant additionally argues that there
“would have been no apparent benefit to Akiyama’s desired sustained drug
release composition by including a microorganism along with the drug;
actually replacing a drug with a microorganism would have rendered the
invention unsatisfactory for its intended purpose of delivering a drug” {id. at
9). We are not persuaded.
The disclosure of Akiyama is not limited to drugs. Instead, Akiyama
discloses “an active ingredient” and states that “[t]here is no particular
limitation on the type of active ingredient.” (FF 1—2 & 6.) The Examiner
relies on both Vandenberg and Tester for teaching the use of a
microorganism as an active ingredient (Ans. 7 (citing Vandenberg 144
(FF 15)) & Ans. 20 (citing Tester, col. 8,11. 8—22) (FF 14))). We agree with
the Examiner that it would have been obvious to substitute one active
ingredient for another (Ans. 20).
CONCLUSION
The evidence supports the Examiner’s conclusion that Akiyama,
Tester, Chapura, and Vandenberg suggest the particles of claims 1 and 24.
We therefore affirm the obviousness rejection of claims 1 and 24. Claims 4,
5, 10-16, 18, 20—22, 25, 27—31, 38, 45, 48—56, and 102 have not been
argued separately and therefore fall with claim 1. 37 C.F.R.
§ 41.37(c)(l)(iv).
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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).
AFFIRMED
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