COMMISSIONER'S DECISION
UNOBVIOUS (Section 45(4)): Advantage Over Prior Art.
A small quantum of invention my suffice for a patent. In a crowded art
slight improvements may sustain a patent. It is often difficult to pre-
dicate results obtainable from chemical substances. Laevolysine is an
essential element of animal diets, but dextro-lysine has no nutritional value.
Held that the process of racemization of dextro-lysine to increase the pre-
sence of laevo-lysine by heating the sulphanite of d-lysine, sulphanilic acid
being a weak acid, is not obvious from the prior racemization of optical
isomers in the presence of strong acids and bases.
FINAL ACTION: Reversed.
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This decision relates to the rejection of claims in application 063891
during conflict proceedings. The application was filed on September 30, 1969
by Stamicarbon N.V., assignee of W. K. van der Linden et al, for an in-
vention for a Process for the Preparation of a Salt of Optically Active
Lysine, Class 260/238.16. The application was found to be in conflict
with another copending application, and during re-examination at the
Section 45(4) stage of the conflict proceedings, three claims were rejected
as being unpatentable in view of certain prior art references. The
rejection was referred to the Patent Appeal Board for review. Since
the applicant did not request a hearing, the review is based upon the
records on file.
The invention is for a process to convert optically active lysine
sulphanilate into an optically inactive form (the racemate or DL
form), which is a mixture of the two optically active forms of lysine.
Lysine is an amino acid which occurs in nature as a constituent of
proteins. The lysine which does occur naturally is the optically
active laevo form (1-lysine) which is an essential component of
animal diets. The other optical form, dextro-lysine (d-lysine)has no
nutritional value. When lysine is made synthetically it is an
optically inactive form consisting of a mixture of laevo and dextro
lysine. It has now been found that the desirable L-form can be
concentrated from the DL-mixture by converting the mixture into the
sulphanilic acid salt, dissolving the salt, and selectively precipitating the
L-lysine from the solution. This process is essentially the same as
prior art processes in which other acids, such as 3,5-dinitrobenzoic acid,
anthraquinone-.beta.-sulphonic acid, 1-chloronaphthalene 4-sulphonic acid or
.beta.-napthalenesulphonic acid are used, but there are certain
advantages in using sulphanilic acid (also called paraminobenzenesulphonic
acid) in place of those acids. The Office considered those advantages
to be unobvious, and concluded during the conflict proceedings that
that phase of the process is patentable.
A further embodiment of the invention involves beating the sulphanilate
of one of the isomers, such as the d-lysine, in an inert solvent.
This process racemates the d-lysine, i.e. it is converted into a
mixture of d & 1 lysine. The racemate so produced can then be treated
as described above to separate out the desired L-form. By this
method it is possible to convert the d-form into the more desired 1-form.
It is this last embodiment which the applicant is now claiming, and
which the examiner has held to be unpatentable.
The examiner applied the following references and found the invention
to be unpatentable in view of them for the reasons stated below.
References Applied
United States Patents
2,586,154 Feb. 19, 1952 Cl. 260-534 Emmiek
3,213,106 Oct. 19, 1965 Cl. 260-319 Sasaji et al
Gilman: Organic Chemistry, Vol. 1, pages 176-181, (1938).
Wheland: Advanced Organic Chemistry, 2nd Edition, pages
250-261, (1951).
Wertheim: Textbook of Organic Chemistry, 2nd Edition,
page 340, (1947).
Holler: Chemistry of Organic Compounds, pages 333-334, (1951).
Fieser and Fieser: Organic Chemistry, 2nd Edition, pages
272-Z74, (1950).
Conflicting claim C12 and claims 2 and 3 are rejected in view
of the above cited references. These references describe
the racemization of optically active organic compounds to
produce the racemate mixture thereof by heating the optically
active organic compounds in inert solvents; and in particular
the racemization of optically active ~ -amino acids by heating
to temperature between about 150· and 200·C in inert solvents.
The process claimed in claim C12 (claim 1) and claims 2 and 3
fail to patentably distinguish over the cited references as
the claims claim the racemization of optically active lysine
sulphanilate by heating in an inert solvent.
The applicant argued on November 30, 1972 that the references were
inapplicable for the following reasons:
United States Specification 2,586,154 discloses that D-
lysine (and of course also L-lysine, but this is not
important in practice) can be racemised by heating it with
hydrochloric acid (column 1, lines 51-52) or by heating
either free D-lysine or D-lysine monohydrochloride in
combination with phosphoric acid (column 2, lines 52-54).
United States Specification 3,213,106 discloses (column 2,
lines 1-15) that D-lysine can be racemised in water,
preferably in the presence of approximately equimolecular
amounts of acid to avoid decomposition of the amino acid.
In addition to hydrochloric acid other strong acids such as
sulfuric acid, phosphoric acid, oxalic acid, trichloroacetic
acid and the like are also effective in equivalent amounts.
The cited textbooks disclose only general considerations in
respect of racemisation and are less relevant than the above
mentioned United States Specifications.
In the racemisation process as claimed in the present application
D-lysine is racemised in the presence of an equimolecular
amount of sulphanilic acid (which is in fact an internal salt
having weaker acidic properties than the strong acids mentioned
in United States Specification 3,213,106). There is thus prepared,.
without any perceptible decomposition, a DL-lysine-salt having
a special property, namely, that it can be optically resolved
by the method of selective crystallization.
At the priority date of the present application there were
only four DL-lysine salts known with the same property as
DL-lysinesulphanilate. These salts are mentioned in the Dutch
patent application 6,711,971 published 1st March 1968 (The
United States Specification 3,527,776 corresponds with this
publication) and are discussed in the present application at
page 2, paragraph 2. Three of the said known DL-salts are less
suitable for the selective crystallization because of the low
yield and low optical purity of the crystallized salt. The
fourth salt (the salt of DL-lysine with 3,5 dinitrobenzoic acid)
is more suitable for the selective crystallization. However,
this DL-salt cannot be prepared by racemization of the corresponding
D-lysine-salt because a strong decomposition takes place (see
lines 14-16, page 2 of the description). Whether or not, the other
three known DL-salts can 6e prepared by the racemisation process
as claimed has not been tested.
In the cited references, nothing is disclosed in respect of
the preparation of a DL-lysine salt having the above-mentioned
special property. The salts of DL-lysine and the strong
acids mentioned in United States Specification 3,213,106 do
not have such property. The relevant art in this connection
is the said Dutch application 6,711,971. However, not just any
DL-lysine salt with the said property can be prepared according
to the claimed racemisation method and not just any acid is in
general suitable in the racemisation of D-lysine.
The preparation of DL-lysinesulphanilate by racemisation of
D-lylinesulphanilate is consequently a new and unobvious process,
because of first the new and unobvious property oœ the DL-salt
prepared. Secondly, because sulphanilic acid is an internal
salt with weak acidic properties and the use of such an 'acid'
is unobvious in view of United States Specification 3,213,106.
Thirdly, the known other DL-lysine salt having the same property
(salt with 3,5-dinitrobentoic acid) cannot be prepared by the
same method.
In a latter response, on June 11, 1973, he added the following
comments:
(1) D-lysine could be racemized without any perceptible
decomposition by heating an aqueous solution of D-lysine
in the presence of an equimolecular amount of a strong acid
(U.S. spec. 3,213,106).
(2) Four salts of DL-lysine with an optically inactive acid could
be optically resolved by the method of selective crystallization
(U.S. spec. 3,527,776 corresponding with Dutch spec. 6,711,971).
At the priority date of the present application it was not
known that by heating an aqueous solution of D-lysine in the
presence of an equimolecular amount of sulphanilic acid, being
an internal salt with weak acidic properties, a salt of
DL-lysine could be prepared without any perceptible decomposition
and having the same property as the four known DL-lysine salts
mentioned in U.S. spec. 3,827,776.
To demonstrate the unobviousness of the claimed process, we
enclose results of comparative experiments. These experiments
relate to the racemization of D-lysine-sulphanilate and of the salt of
D-lysine with 3,5-dinitrobenzoate acid. The DL-lysine salt
of this acid is the most suitable salt in respect of the select-
ive crystallization which was known at the priority date of the
present application.
What the Board must do is analyse the prior art, which discloses closely
related inventions, to determine whether such differences as do exist
suffice for a holding that the new process would have been unobvious
to a skilled chemist when the application was filed.
Racemization of optical isomers, as shown in by the text book refer-
ences cited by the, examiner, is well known. Racemization of lysine itself
was also known in the presence of strong acids and bases. Heretofore,
however, no one had prepared the sulphanilic acid salts of lysine, nor
racemized that salt. It was the position of the examiner that because
of the prior art it would hive been obvious to racemize the sulphanilic
acid in order to increase the production of L-lysine, and equally it
would have also been evident that the process would work. While
there is some justification for such a conclusion, we have reservations
about coming to it. The prior art racemizations of lysine were done
in the presence of strong acids, such as hydrochloric and trichlor-
acetic acids. Sulphanilic acids, by contrast is an internal salt
having relatively weakly acidic properties. At the priority date
of the application only four salts of lysine were known to be
useful for selective crystallization of lysine, and attempts to
racemate at least one of those led to considerably more decomposition
than when lysine sulphanilate is used. Consequently we have come
to the conclusion that there is a reasonable doubt that the
racemization being claimed would have been obvious, or that the
Commissioner could be satisfied within the meaning of Section 42
that the applicant is not entitled to a patent.
Admittedly the quantum of invention present is small, but if any
is present, that will suffice for s patent. This is a crowded art,
where slight improvements might sustain a patent. The Office s
previous conclusions that the separation of lysines using sulphanilic acid
itself is patentable is testimony to that. It is also supported by a long
line of judicial decisions. See, for example, Jamb Sets v Carlton
1964 Ex. C.R. 377, Scragg & Sons v. Leesona, 1964 Ex. C.R. 649 or
Wright & Carson v Brake Service 1925 Ex. C.R. 127 at 131. Furthermore,
as was observed by Maclean, J. in Chipman Chemists v. Fairview Chemical
1932 Ex. C.R. 107 it is often difficult to predicate the results that
may be obtained from chemical substances:
... Where chemical action is involved analogy
does not carry one far...
We have reached the conclusion that in this instance there may well
be invention present, and that the application should be allowed to
proceed.
There is one other matter for consideration. The applicant has
proposed an amendment to claim C12 which relates the racemization
process to the selective crystallisation process. Whether this
alteration is made or not is immaterial to the conclusion we have
reached, and should be left for the consideration of the examiner
during subsequent prosecution.
Gordon Asher,
Chairman,
Patent appeal Board.
I concur with the finding of the Patent Appeal Board. The re-
jection is to be withdrawn, and prosecution resumed.
Decision accordingly,
A.M. Laidlaw,
Commissioner of Patents.
Dated at Hull, Quebec,
this 9th. day of
September, 1974.
Agent for Applicant
Fetherstonhaugh & Co.
Ottawa, Canada C.D. 210