Ex parte Monte

Board of Patent Appeals and Interferences

Oct 24, 2000

08395867 (B.P.A.I. Oct. 24, 2000)

Application for patent filed February 28, 1995. According to appellant, this application is a1
continuation of application 08/123,794 filed September 20, 1993, now abandoned.
As acknowledged by appellant, "Claim 6 is objected to because in line 8 "bone" should be --2
bovine--. Applicant endeavors to correct this informality at the conclusion of this Appeal" (brief, p. 2).
However, this error in claim 6 has not been corrected by amendment as of the mailing date of this decision.
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and is not binding precedent of the Board.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. 11
UNITED STATES PATENT AND TRADEMARK OFFICE
____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________
Ex parte WOODROW C. MONTE
____________
Appeal No. 1997-3537
Application No. 08/395,8671
____________
ON BRIEF
____________
Before WINTERS, SPIEGEL, and SCHEINER, Administrative Patent Judges.
SPIEGEL, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the examiner's final
rejection of claims 1 through 14, which are all of the claims pending in this application.2
Claims 1 and 2 are illustrative and read as follows:
Appeal No. 1997-3537
Application No. 08/395,867
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1. An article of manufacture for use in altering the appearance to the
immune system of an infant of protein sections of bovine serum albumin,
said article of manufacture comprising
(a) a sealed container;
(b) a nutritionally balanced milk formulation in said sealed
container, said milk formulation including bovine serum
albumin and including an active protease enzyme in a
concentration of 0.025 to 100 milligrams of said enzyme per
liter of said milk formulation, said protease enzyme in said
container cleaving protein-to-protein bonds to alter the
structure of said bovine serum albumin.
2. A dietary enzymatic process for enabling the immune system of an
infant to distinguish between the ABBOS amino acid section of bovine
serum albumin and the p69 amino acid section of insulin-producing beta
cells, comprising the steps of
(a) preparing an infant milk formula, said infant milk formula being
prepared by
(i) sterilizing a milk formulation including bovine serum
albumin;
(ii) adding a sterilized protease enzyme to said milk
formulation in a concentration of 0.025 to 100
milligrams of said enzyme per liter of said milk
formulation;
(b) packaging said infant milk formula prepared in step (a) in a
sealed container such that while said milk formula is in said
container, said protease enzyme cleaves peptide bonds of
said bovine serum albumin to alter the ABBOS amino acid
section of the bovine serum albumin such that anti-ABBOS
antibodies produced by an infant ingesting said infant milk
formula will not attack the p69 amino acid section of insulin-
producing beta cells in the infant; and,
(c) feeding the infant by opening said container and administering
said infant milk formula to the digestive tract of the infant such
that the infant's immune system is exposed to the altered
ABBOS amino acid section of the bovine serum albumin.
Appeal No. 1997-3537
Application No. 08/395,867
Made of record by the examiner on the PTO-849 attached to the Office action mailed July 11,3
1995 (Paper No. 2).
Appellant has apparently inverted the journal title to "American Scientific" on p. 8 of the brief.4
The examiner has withdrawn the final rejection of claims 1-14 under 35 U.S.C. § 112, second5
paragraph, regarding the term "partially" (answer, p. 3).
- 3 -
The references relied on by the examiner are:
Thibault 4,981,704 Jan. 1, 1991
Martinez et al. (Martinez) 5,405,637 Apr. 11, 1995
(filed Jun. 30, 1993)
Karjalainen et al. (Karjalainen), "A Bovine Albumin Peptide as a Possible Trigger of
Insulin-Dependent Diabetes Mellitus," The New England Journal of Medicine, Vol. 327, No.
5, pp. 302-307 (July 30, 1992)
A reference relied on by the appellant (brief, p. 8) is:
J. Rennie, "Formula for Diabetes: Cow's milk for infants may contribute to the disease,"
Scientific American, Vol. 267, No. 4, pp. 24-25 (October 1992).3,4
ISSUE5
Claims 1-14 stand rejected under 35 U.S.C. § 103(a) as unpatentable over Thibault
or Martinez either in view of Karjalainen. We REVERSE.
In reaching our decision in this appeal, we have given careful consideration to the
appellant's specification and claims and to the respective positions articulated by the
appellant and the examiner. We make reference to the examiner's answer (Paper No. 9,
mailed March 6, 1997) for the examiner's reasoning in support of the rejections and to the
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Application No. 08/395,867
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appellant's brief (Paper No. 8, filed December 16, 1996) for the appellant's arguments
thereagainst.
BACKGROUND
As explained by Karjalainen (p. 302):
Abstract Background. Cow's milk has been implicated as a possible
trigger of the autoimmune response that destroys pancreatic beta cells in
genetically susceptible hosts, thus causing diabetes mellitus. Studies in
animals have suggested that bovine serum albumin (BSA) is the milk protein
responsible, and an albumin peptide containing 17 amino acids (ABBOS)
may be the reactive epitope. Antibodies to this peptide react with p69, a
beta-cell surface protein that may represent the target antigen for milk-
induced beta-cell--specific immunity.
Indeed, all of the diabetic patients studied by Karjalainen had elevated levels of anti-BSA
antibodies (but not of antibodies to other milk proteins), the bulk of which were specific for
ABBOS (abstract, p. 302; p. 303, c. 2, para. 4).
THE INVENTION
The claimed invention is directed to processes for enzymatically hydrolyzing BSA
(claims 6 and 11), in particular its 17 amino acid ABBOS portion (claims 2-5, 10 and 12-
14), in infant milk formula such that antibodies produced by an infant ingesting the
hydrolyzed milk formula will be reactive with an altered, i.e., hydrolyzed, ABBOS epitope
and, consequently, will not attack the p69 protein of the infant's pancreatic beta cells
(claims 2-5, 10 and 14); and, to sealed containers of infant milk formula containing
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Application No. 08/395,867
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hydrolyzing enzyme, i.e., a protease (claims 1 and 7-9). All claims require 0.025 to 100
milligrams of protease per liter of infant milk formula.
OPINION
Thibault and Martinez both describe hypoallergenic milk products containing
partially hydrolyzed whey proteins prepared by enzymatic hydrolysis using a mixture of
chymotrypsin/trypsin. Thibault uses an enzyme mixture having a chymotrypsin/trypsin
activity ratio between 1.5 and 3.0 under defined conditions until the alpha-lactalbumin is
totally eliminated, followed by separation of the enzymes and residual unhydrolyzed
proteins (c. 2, ll. 36-50; c. 3, ll. 46-53), principally serum albumin and immunoglobulins (c.
7, ll. 23-26). Martinez uses an enzyme mixture having a trypsin/chymotrypsin activity ratio
of 1.3 to 18 (i.e., a chymotrypsin/trypsin activity of about 0.8 to about 5.6) to result in a 4 to
10% degree of hydrolysis (c. 2, ll. 11-18; c. 3, ll. 16-21) and discloses packaging infant
formula hydrolysate in any type of conventional container, e.g., glass, plastic, coated metal
cans, etc. (c. 6, ll. 24-26). Optionally, Martinez preheats the protein solution prior to
hydrolysis to insure denaturation of whey protein fractions, e.g., BSA and immunoglobulin
(c. 3, ll. 25-28).
Karjalainen has been discussed above. The examiner found that "Karjalainen
teaches that ABBOS is the BSA peptide responsible for triggering diabetes because anti-
Appeal No. 1997-3537
Application No. 08/395,867
Karjalainen "suggests that an active, antigen-driven immune response against the BSA-derived6
ABBOS peptide is a feature of the autoimmune response in patients with insulin-dependent diabetes. This
likens the disease in humans to that in diabetes-prone rodents, in which the prevention of exposure to cow's
milk early in life prevents the development of the disease." (p. 307, c. 1, ll. 1-7, footnote omitted, emphasis
added).
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BSA antibodies form against ABBOS and subsequently bind to p69, pancreatic beta-cell
surface proteins, causing the development of diabetes" (answer, p. 6).
According to the examiner,
[i]t would have been obvious ... to prepare an infant milk formula ... as
claimed since Thibault and Martinez clearly suggest using proteases to
reduce large peptides in infant milk (BSA)-containing foods, and Karjalainen
teaches that BSA is not desirable in infant milk formulae due to the presence
of ABBOS (a large peptide). ... [R]emoval [of ABBOS prior to infant
digestion] alters the appearance of BSA to an infant's immune system which
prevents the creation of antibodies against ABBOS so that the p69 amino
acid section is not affected. [Answer, para. bridging pp. 6-7.]
However, the examiner has not pointed out, and we do not find, where Karjalainen
discloses or suggests using enzymatically hydrolyzed BSA in milk formulas to prevent
onset of milk-induced diabetes. Rather, Karjalainen appears to suggest preventing
exposure to cow's milk early in life to prevent onset of milk-induced diabetes by analogy to
a diabetes-prone rodent model. 6
Furthermore, to the extent the examiner relies on inherency to establish that "the
hypoallergenic milk formulation is basically the same as the milk formulation claimed"
(answer, p. 9), that reliance appears misplaced for several reasons. First, both Thibault
and Martinez use enzyme mixtures comprising trypsin and chymotrypsin. Karjalainen
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Application No. 08/395,867
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explicitly states that trypsin "leaves much of the ABBOS sequence intact" (p. 306, c. 2).
Second, Thibault explicitly states that albumin is "hydrolysable with the most difficulty by the
enzyme system adopted," and explicitly states that serum albumin and immunoglobulins
are the principal "residual proteins" left by the described trypsin/chymotrypsin enzyme
system (c. 7, ll. 23-26). Similarly, Martinez describes an "optional preliminary step prior to
hydrolysis ... [of] preheating of the protein solution to insure denaturation of whey protein
fractions, e.g., serum albumin (BSA) and immunoglobulins (particularly IgG)" (c. 3, ll. 25-
28). Thus, Martinez also suggests that the disclosed trypsin/chymotrypsin enzyme system
may not be effective to hydrolyze BSA. Third, while Martinez states that its hydrolysate "is
preferably devoid of detectable intact milk protein" (c. 4, ll. 18-20), the examiner has not
established on this record that the loss of "detectable intact milk protein" necessarily
means that the milk proteins have been hydrolyzed, i.e., cleaved, as opposed to denatured
such that their quaternary structure is simply unfolded somewhat. Thus, it is unclear on this
record that the enzymatic hydrolysis steps of Thibault or Martinez will inherently result in the
claimed invention. In other words, the examiner has not established a factual basis upon
which to conclude that the trypsin/chymotrypsin hydrolysis method and resulting hydrolysate
of Thibault or Martinez would reasonably be expected to hydrolyze BSA, in particular its
ABBOS sequence so as to result necessarily in the claimed invention.
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Application No. 08/395,867
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Based on this record, we find that the examiner has relied on impermissible
hindsight in making her determination of obviousness. In re Fritch, 972 F.2d 1260, 1266,
23 USPQ2d 1780, 1784 (Fed. Cir. 1992) (“It is impermissible to engage in hindsight
reconstruction of the claimed invention, using the applicant’s structure as a template and
selecting elements from references to fill the gaps”).
Accordingly, the rejection is reversed.
CONCLUSION
To summarize, the decision of the examiner to reject claims 1-14 under
35 U.S.C. § 103(a) as unpatentable over Thibault or Martinez either in view of Karjalainen
is reversed.
REVERSED
SHERMAN D. WINTERS )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
CAROL A. SPIEGEL ) APPEALS
Administrative Patent Judge ) AND
) INTERFERENCES
)
)
TONI R. SCHEINER )
Administrative Patent Judge )
Appeal No. 1997-3537
Application No. 08/395,867
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TOD R. NISSLE
TOD R. NISSLE, P.C.
P.O. BOX 55630
PHOENIX, ARIZONA 85078
CAS/cam
APPEAL NO. 1997-3537 - JUDGE SPIEGEL
APPLICATION NO. 08/395,867
APJ SPIEGEL
APJ SCHEINER
APJ WINTERS
DECISION: REVERSED
Prepared By: Cheryl
DRAFT TYPED: 24 Sep 01
FINAL TYPED: 13 Oct 00