Ex Parte Averback

Board of Patent Appeals and Interferences

Feb 6, 2002

08482768 (B.P.A.I. Feb. 6, 2002)

The opinion in support of the decision being entered today was not written for
publication and is not binding precedent of the Board.

Paper No. 24

UNITED STATES PATENT AND TRADEMARK OFFICE

__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte PAUL AVERBACK
__________

Appeal No. 1999-0494
Application 08/482,768
__________

ON BRIEF
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Before WILLIAM F. SMITH, ADAMS, and GRIMES Administrative Patent Judges.

WILLIAM F. SMITH, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134 from the final rejection of claims 13
through 15 and 17 through 21, all the claims pending in the application.
Claims 13, 14, and 15 are representative of the subject matter on appeal and
read as follows:
13. A composition comprising (a) a therapeutically effective amount of a compound
that inhibits formation of amyloid fibrils when administered, at an in-tissue concentration
of about 10-5 M or less, to a test animal that has received an intracerebral injection of
DMS and (b) a pharmaceutically acceptable carrier, wherein said composition is
capable of crossing the blood-brain barrier.
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14. The composition as claimed in claim 13, wherein said compound inhibits
formation of amyloid fibrils by acting on DMS components such that a structural
transition of DMS protein in the brain to a β-pleated sheet conformation is prevented.

15. The composition as claimed in claim 13, wherein said compound is selected from
the group consisting of pyrimethamine, cromolyn sodium, erythromycin, purpurogallin,
tartrazine, sulfanilamide, benzopurpurine 4B, 29H, 31H-phthalocyanine, 5-methyl-2-
thiouridine and 1,2-benzylsoxazole.

The references relied upon by the examiner are:
Haber et al. (Haber) 3,728,452 Apr. 17, 1973
Johnson 4,064,248 Dec. 20, 1977

The Merck Index, Eleventh Edition, page 1264, No. 7963
Claims 13 through 15 stand rejected under 35 U.S.C. § 112, fourth paragraph, as
being in improper form. Claims 13 through 15 and 17 through 21 stand rejected under
35 U.S.C. § 103(a). As evidence of obviousness, the examiner relies upon "Merck,
Johnson, and Haber." We reverse. In addition, we make a new ground of rejection
under the provisions of 37 CFR § 1.196(b).
BACKGROUND
The claimed invention is directed to a composition which comprises a
therapeutically effective amount of a compound in a pharmaceutically acceptable
carrier. The composition must be capable of crossing a blood-brain barrier. The
compound is defined in claims 13 and 14 in a functional manner while claim 15 sets
forth a Markush group of compounds which possess the functional requirements of
claim 13.
As seen from claim 13, the compound must inhibit formation of amyloid fibrils
when administered to a test animal under certain conditions. The conditions include an
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intracerebral injection of DMS. DMS is an acronym for "dense microspheres."
Specification, page 4. As explained:
A microscopic structure referred to as the dense microsphere is known to
exist in normal brain and in brain affected by Alzheimer's disease. See
Averback, Acta Neuropathol. 61: 148-52 (1983); results confirmed by Hara, J.
Neuropath. Exp. Neurol. (1986). Evidence for the existence of dense
microspheres (DMS) comes from microscopic histological section studies of fixed
whole brain tissue, where the dense microspheres are seen to have a
proteinaceous central region ("DMS protein") surrounded by continuous
membrane ("DMS membrane"). The dense microspheres are observed as
randomly dispersed, very infrequent structures which occupy an estimated 10-9 or
less of total brain volume, at a unit frequency roughly estimated at
10-16 or less, relative to other definable brain structures such as mitochondria.

Id. Appellant believes that development of amyloid fibrils associated with a number of
conditions including Alzheimer's disease is tied to the unchecked disruption of DMS
in vivo. Specification, page 8. Appellant describes a screening procedure for identifying
compounds which inhibit the disruption of DMS in vivo. As explained:
It has also been discovered that compounds which are effective, at a in-
tissue concentration of about 10-5 M or less, in impeding the formation of amyloid
fibrils in test animals which receive DMS via intracerebral injection can be used
to treat cerebral amyloidosis, including Alzheimer's disease. Particularly effective
in this regard are compounds that act on DMS protein or DMS membrane, for
example, via intracellular or extracellular binding, so as to prevent a structural
transition of DMS protein in the brain to a β-pleated sheet conformation.

Specification, page 8, lines 15-26.
Example 2 of the specification describes use of this assay to identify compounds
meeting the requirements of claim 13. Of the seven compounds tested in Example 2,
appellant states that only three compounds, pyrimethamine, cromolyn sodium, and
erythromycin were found to inhibit amyloid formation in vivo at in-tissue levels in the
range of 10-5 to 10-6 M. On the basis of those results, appellant states that those three
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compounds are suitable for use in the treatment method of the present invention.
Specification, page 32.
DISCUSSION
1. Rejection under 35 U.S.C. § 112, fourth paragraph
The examiner's reasoning in support of this rejection is:
The claims relate to the intended use of the composition. Therefore, they are not
a proper definition of the composition as they are not limiting of the composition
per se.

Examiner's Answer, page 3.
The examiner's statement of the rejection is all but incomprehensible and lacks
logic. First, it is not clear why claim 13, an independent claim, is subject to this
rejection. Nor is it clear why claim 15 is subject to this rejection as that claim is limited
to a Markush group of specific compounds useful in the composition of claim 13.
It appears that the examiner's concern in terms of proper dependency is limited
to claim 14. But neither statement by the examiner explains why claim 14 does not
serve to further limit claim 13. On its face, claim 14 is directed to a narrower subgenus
of compounds than those required by claim 13 in that the compounds of claim 14,
besides possessing the property required by claim 13, must also inhibit formation of
amyloid fibrils by the activity described in claim 14.
While not clear from the statement of the rejection, it may be the examiner's
concern that not all of the compounds described by appellant in the specification
possess the properties required by both claims 13 and 14. In other words, appellant
may not have described in the specification compounds possessing the property of
claim 13 but not the property of claim 14. If so, those question would be properly raised
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under the enablement requirement of 35 U.S.C. § 112, first paragraph, not the
dependency requirement of the fourth paragraph of this section of the statute.
The examiner's rejection under 35 U.S.C. § 112, fourth paragraph, is reversed.
2. Obviousness
The examiner's facts and reasoning in support of the rejection under this section
of the statute are:
Merck teaches purpurogallin used as a pharmaceutical to retard oxidation,
Johnson teaches at column 1, lines 25-30 the use of cromolyn sodium as an
antiasthmatic drug and Haber et al at column 1, lines 4-67 teaches the use of
pyrimethamine in a pharmaceutical composition. The compositions of claims 13-
15 and the mode and means of administration of claims 17-21 are obviated
under 35 U.S.C. 103 since an intended use limitation does not render the
composition unobvious. See In re Skoner, 186 USPQ 80, (CCPA 1975); In re
Kalm 154 USPQ 10 (CCPA 1967); In re Halley 132 USPQ 16 (CCPA 1961).
For these reasons the claimed subject matter is deemed to fail to
patentably distinguish over the state of the art as represented by the cited
references. The claims are therefore properly rejected under 35 U.S.C. 103.

Examiner's Answer, pages 3-4. The examiner further explains the rejection stating "the
rejection of claims 13-21 [sic, 13-15, 17-21] under 35 USC 103 (a) is deemed proper
since the compositions claimed are taught by the art." Id., page 5.
The examiner's position on appeal as to why the subject matter of any individual
claim would have been obvious to one of ordinary skill in the art under this section of the
statute is difficult to discern. By the examiner's statement, that the "compositions
claimed are taught by the art" bespeaks of an anticipation rejection under 35 U.S.C.
§ 102, not an obviousness rejection under 35 U.S.C. § 103. Furthermore, the
examiner's fact finding is open to question in regard to certain of the applied references.
For example, the examiner states that the Merck Index teaches "purpurogallin used as a
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pharmaceutical to retard oxidation." The record copy of the Merck Index is difficult to
read due to the photocopy supplied by the examiner but it does not appear to use the
word "pharmaceutical."
In any event, the examiner's statement of the rejection under 35 U.S.C. § 103(a)
is fundamentally deficient in that it does not address the subject matter of the claims as
a whole. As seen from claim 13, the composition must be "capable of crossing the
blood-brain barrier." Nowhere in the Examiner's Answer does the examiner explain how
any of the references relied upon teaches or suggests this aspect of the claimed subject
matter.
The examiner's rejection under 35 U.S.C. § 103(a) is reversed.
NEW GROUND OF REJECTION UNDER 37 CFR § 1.196(b)
Under the provisions of 37 CFR § 1.196(b), we make the following new ground of
rejection.
Claims 13-15 and 17-21 are rejected under 35 U.S.C. § 102(b). As evidence of
anticipation, we rely upon Johnson.
1. Claims 13-15
For ease of explaining the facts and reasoning in support of the new ground of
rejection, we will consider these three claims as a group.
In considering claims 13, 14 and 15 together, it is apparent that cromolyn sodium
meets the functional requirements of both claims 13 and 14 in terms of inhibiting
formation of amyloid fibrils as confirmed by the results of Example 2 of the present
specification.
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Johnson describes pharmaceutical compositions comprising cromolyn sodium
and a pharmaceutically acceptable carrier. See, e.g., column 1, lines 57-66 of Johnson.
The question becomes twofold. First, does Johnson describe a cromolyn sodium
containing pharmaceutical composition which contains cromolyn sodium in the
"therapeutically effective amount" of the claims? Second, is the cromolyn sodium
pharmaceutical composition described in Johnson "capable of crossing the blood-brain
barrier?"
In regard to the "therapeutically effective amount" language of claim 13 on
appeal, we note that the claim does not specifically state what the therapeutic effect of
the composition is to be. The claim language regarding inhibiting formation of amyloid
fibrils is directed to a property of the active agent, here, cromolyn sodium, not to the
amount of the active agent to be present in the composition. Thus, the pharmaceutical
composition described in Johnson, of necessity, contains a "therapeutically effective
amount" of cromolyn sodium, at least for the purposes described in Johnson. In other
words, the "therapeutically effective amount" language of claim 13 does not serve to
distinguish the claimed composition from those described in Johnson.
Turning to the other possible point of distinction between the respective
compositions, i.e., the requirement of claim 13 that the composition is capable of
crossing the blood-brain barrier, we note that Johnson does not discuss this property
whatsoever. However, this does not mean that claims 13-15 are patentably distinct
from the cromolyn sodium compositions described in Johnson.
Under these circumstances, it is reasonable to shift the burden to applicant to
provide evidence establishing in the first instance that the cromolyn sodium
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pharmaceutical compositions described in Johnson do not possess this property. As
stated in In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-434 (CCPA 1977):
Where, as here, the claimed and prior art products are identical or
substantially identical, or are produced by identical or substantially identical
processes, the PTO can require an applicant to prove that the prior art products
do not necessarily or inherently possess the characteristics of his claimed
product. . . . Whether the rejection is based on `inherency' under 35 U.S.C. §
102, on `prima facie obviousness' under 35 U.S.C. § 103, jointly or alternatively,
the burden of proof is the same, and its fairness is evidenced by the PTO's
inability to manufacture products or to obtain and compare prior art products
[footnote omitted].

If in future proceedings evidence is provided establishing that the cromolyn
sodium pharmaceutical compositions of Johnson do not possess this property, the
examiner would need to evaluate Johnson under 35 U.S.C. § 103 in light of other
relevant prior art to determine whether the claimed compositions, to the extent that they
include cromolyn sodium, would have been obvious. If on the other hand it turns out
that the cromolyn sodium pharmaceutical compositions described in Johnson do
possess this property, applicant's observation of this property, as opposed to the silence
of Johnson, does not mean that the compositions of claims 13-15 are patentable. As
stated in In re Spada, 911 F.2d 705, 708, 15 USPQ2d 1655, 1657 (Fed. Cir. 1990)
(citations omitted) "discovery of a new property or use of a previously known
composition, even when that property and use are unobvious from the prior art, can not
impart patentability to claims to the known compositions."
2. Claims 17-21
These claims further limit claim 13 in regard to the pharmaceutically acceptable
carrier (claim 17), that the composition be orally, rectally, or nasally acceptable (claims
18-20) and the composition be in spray or aerosol form (claim 21). Johnson describes a
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wide range of forms in which the cromolyn sodium compositions of that invention may
be administered. Johnson, column 1, line 67 - column 3, lines 22. Specifically, Johnson
describes that the cromolyn sodium may be dissolved in water with salt added to
provide an isotonic solution. Johnson, column 2, lines 62-65. Johnson also explicitly
teaches that the cromolyn sodium compositions may be orally administered or nasally
administered in spray or aerosol form. See, e.g., Johnson, column 1, line 67 - column
2, line 12, column 2 line 48-column 3, line 22. While Johnson does not explicitly state
that the composition is "rectally acceptable" as required by claim 19, we note that the
liquid formulations described in Johnson would appear to be "rectally acceptable" as
would any aqueous liquid formulation.
TIME PERIOD FOR RESPONSE
This opinion contains a new ground of rejection pursuant to 37 CFR
§ 1.196(b). 37 CFR § 1.196(b) provides that, “A new ground of rejection shall not be
considered final for purposes of judicial review.”
37 CFR § 1.196(b) also provides that the appellant, WITHIN TWO MONTHS
FROM THE DATE OF THE DECISION, must exercise one of the following two options
with respect to the new ground of rejection to avoid termination of proceedings
(§ 1.197(c)) as to the rejected claims:
(1) Submit an appropriate amendment of the claims so rejected or a
showing of facts relating to the claims so rejected, or both, and have the
matter reconsidered by the examiner, in which event the application will be
remanded to the examiner. . . .

(2) Request that the application be reheard under § 1.197(b) by the
Board of Patent Appeals and Interferences upon the same record. . . .
No time period for taking any subsequent action in connection with this appeal

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may be extended under 37 CFR § 1.136(a).
The examiner’s decision is reversed.
REVERSED; 196(b)

)
William F. Smith )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Donald E. Adams )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Eric Grimes )
Administrative Patent Judge )
Appeal No. 1999-0494
Application 08/482,768

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ELD