COMMISSIONER'S DECISION SUMMARY
C.D. 1206 ....Application No. 529,362 (B20, B22, C00)
Claims rejected as being broader than the disclosure
The examiner rejected certain claims of the application on
the grounds that they were broader than the invention disclosed
since they claimed the preparation of monoclonal antibodies the
preparation of which had not been adequately disclosed. The
Board ruled that the claims had been properly rejected and
recommended that the rejection be upheld.
IN THE CANADIAN PATENT OFFICE
DECISION OF THE COMMISSIONER OF PATENTS
Patent application number 529,362, having been rejected under
Subsection 47(2) of the Patent Rules, the Applicant asked that
the Final Action of the Examiner be reviewed. The rejection has
consequently been considered by the Patent Appeal Board and by
the Commissioner of Patents. The findings of the Board and the
ruling of the Commissioner are as follows:
Agent for Applicant
Goudreau Gage Dubuc & Martineau Walker
3400, La Tour de la Bourse
Case Postale 242, Place Victoria
Montreal, Quebec
H4Z 1E9
This decision deals with the Applicant's request that the
Commissioner of Patents review the Examiner's Final Action on
patent application number 529,362 (Class 195-1.105) filed on
February 10, 1987 for an invention entitled "NEW RETROVIRUS
CAPABLE OF CAUSING AIDS, MEANS AND METHODS FOR DETECTING IT IN
VITRO". The inventors are Luc Montagnier; Solange Chamaret;
Denise Guetard; Marc Alizon; Fran‡ois Clavel; Mireille Guyader;
Pierre Sonigo; Fran‡oise Brun-Vezinet; Marianne Rey; Christine
Rouzioux and Christine Katlama and the application is assigned to
Institut Pasteur. The Examiner in charge of the application
issued the Final Action on October 8. 1993 refusing claims 11 to
34, 40, 43 to 54 and 70 and, by implication, declaring claims 1
to 10, 35 to 39, 41, 42, 55 to 69 and 71 to 73 to be allowable.
The Applicant replied on April 8, 1994 requesting a review by the
Commissioner of Patents and an oral hearing before the Patent
Appeal Board. Consequently an oral hearing was held on January
18, 1995 at which Denise Huberdeau, Danielle Banerman and
Stephane Drouin represented the Applicant. Drs. Isaac Ho and
Linda Brewer represented the Patent Branch and the Board was
comprised of Peter Davies as Chairman and Drs. Michael Howarth
and Effat Maher as members.
The application, as outlined in the abstract, relates to a new
class of retrovirus named HIV-2; to antigens obtained from this
virus, namely proteins p12, p16, p26 and glycoprotein gp140, and
to immunogenic compositions containing these antigens,
particularly glycoprotein gp140. The antigens are used for the
in vitro diagnosis in man for potentiality of certain forms of
AIDS. The application also relates to the application of cloned
DNA sequences derived from the RNA of HIV-2 as probes in
diagnostic kits.
In her Final Action, the Examiner rejected claims 11 to 16, 21,
34, 40, 47, 52, 53, 54 and 70 of the application under Subsection
34(2) of the Patent Act as being indefinite and not supported by
the disclosure. The Examiner also rejected claims 11 to 33 and
43 to 51 under Subsection 39(1) of the Act.
In its response dated April 8, 1994 the Applicant submitted a new
set of claims comprising claims 1 to 93 for consideration by the
Board and on January 17, 1995, immediately prior to the oral
hearing, a further set of claims making minor, mostly editorial
changes to the claims previously submitted. Since the claims
submitted on January 17, 1995 are similar to those submitted on
April 8, 1994 the Board has decided to consider the latter set of
claims in this decision but sees no reason why the former set of
claims may not be considered by the Examiner at the conclusion of
these proceedings.
In arguing against the rejection of claims 11 to 29 and 55 to 66
(former claims 11 to 33 and 43 to 51) under Subsection 39(1) of
the Act, the Applicant stated that the claims were directed to
compounds used as diagnostic agents rather than as medicines and
as such did not fall within the scope of the Subsection. The
Board accepts this argument as persuasive in overcoming the
rejection and recommends that the rejection based on these
grounds be withdrawn. Furthermore after reviewing the claims
submitted on April 8, 1994 the Board is satisfied that claims 1
to 60, 67 to 83 and 86 to 93 avoid the objections made by the
Examiner leaving only claims 61 to 66, 84 and 85 under rejection.
Accordingly the oral hearing was limited to argument directed
towards claims 61 to 66, 84 and 85 only.
Subsequent to a discussion held during the oral hearing the
Applicant, on February 10, 1995, filed an amended set of claims
61 to 66 which, in the Board's opinion, overcome the Examiner's
objection to the claims; the Board therefore recommends that the
amended claims be accepted as allowable.
The only remaining claims under rejection are therefore claims 84
and 85 and the remainder of this decision will be addressed to
these claims which are as follows:
Claim 84 Antibody according to any one of claims 78 to 83, characterized in
that it is monoclonal.
Claim 85 The hybridoma secreting the monoclonal antibody according to
claim 84.
In the Final Action, the Examiner rejected claim 53 (now claim
84) directed to a monoclonal antibody and claim 70 (now claim 85)
directed to the hybridoma secreting the monoclonal antibodies
stating the following:
Objection to claims 53 and 70 (previously 49 and 66, respectively) for lack of
specific support in the disclosure is maintained. Applicant has not prepared any
hybridomas or monoclonal antibodies. Applicant has suggested that monoclonal
antibodies are a reasonable extension of the alleged invention and that the crucial
inventive step in the preparation of monoclonal antibodies lies in obtaining the
antigens to which these antibodies bind. Applicant has argued that specific
exemplary support would simply consist of including in the disclosure, standard
procedures for hybridoma and monoclonal antibody preparation.
The examiner agrees that once an antigen is available, a hybridoma and a
monoclonal antibody can be prepared using well established techniques. While the
path to a monoclonal antibody may be obvious, the product of that path is not
obvious. If it were, there would be nothing inventive about the product. A
product cannot be both obvious and inventive at the same time. Applicant has not
prepared a hybridoma or a monoclonal antibody. Applicant is claiming something
that he cannot describe in terms of a structure, or in terms of physical or chemical
properties. He is, in fact, claiming hoped-for products which have been described
only in terms of a biological activity or utility. The disclosure of a patent
application is addressed to one skilled in the art to which the invention relates and
must be written such that one skilled in the art would be able to put the invention
to the same successful use as the inventor. Applicant has not shown that he was
successful in the production of hybridomas or monoclonal antibodies and therefore
fails to provide sufficient support for claims to these products.
The questions before the Board are whether or not the
specification describes correctly and fully the preparation and
the properties of the hybridoma and the monoclonal antibodies
claimed in claims 84 and 85, and whether or not such description
is set out in such clear concise terms as to enable a person
skilled in the art to make and use the invention as required by
Subsection 34.(1) of the Patent Act which reads as follows:
An applicant shall in the specification of his invention
(a) correctly and fully describe the invention and its operation or use as
contemplated by the inventor;
(b) set out clearly and fully the various steps in a process, or the method of
constructing, making, compounding or using a machine, manufacture or
composition of matter, in such full, clear, concise and exact terms as to enable any
person skilled in the art or science to which it appertains, or with which it is most
closely connected, to make, construct, compound or use it;
(c) in the case of a machine, explain the principle thereof and the best mode in
which he has contemplated the application of that principle;
(d) in the case of a process, explain the necessary sequence, if any, of the various
steps, so as to distinguish the invention from other inventions; and
(e) particularly indicate and distinctly claim the part, improvement or combination
that he claims as his invention.
(Emphasis added)
In the present case, the question with regard to Subsection
34.(1)(a) is whether the written description of the application
provides sufficient detailed information for any person skilled
in the art to produce and characterize the claimed monoclonal
antibodies and the hybridomas secreting such antibodies. The
Board finds that the only guidance or direction given for the
preparation of the embodiments of claims 84 and 85 in the
specification is that given on page 50 of the disclosure as
follows:
. . . It [the invention] also relates to the monoclonal antibodies which can be
produced by traditional techniques, these monoclonal antibodies being directed,
respectively, more specifically against the different proteins of HIV-2.
These polyclonal or monoclonal antibodies can be used in different
applications. Their use for neutralizing the corresponding proteins, or even
inhibiting the infectivity of the whole virus, will mainly be mentioned. They can
also be used, for example, for demonstrating the viral antigens in biological
preparations or for carrying out procedures for purification of the corresponding
proteins and/or glycoproteins, for example by using them in affinity
chromatography columns.
The Board cannot find any description of the hybridoma of claim
85 or any description of a method of preparing it provided in the
above cited statements or in the entire description. No specific
description of the monoclonal antibodies in claim 84 or a process
for their preparation is disclosed. The only guidance as to the
description of the monoclonal antibodies and the process by which
they may be prepared is that they can be prepared by "traditional
techniques." The sole specific technical teaching provided is
the identity of the antigens. Describing and identifying the
antigens does not provide support for the hybridoma or the
monoclonal antibodies nor does it provide sufficient instruction
on how to make the antibodies.
The Applicant's description of the monoclonal antibodies as
neutralizing or binding with the antigens is not considered a
specific description. The term antibody denotes a material that
opposes and neutralizes a body in this case, the body is the
antigen. An antibody must fit and bind with a particular antigen
otherwise it would not be called an antibody. The antibody is
expected to have the property of binding to the antigen because
it is presumed to be an antibody for that antigen. The
Applicant's description makes an unwarranted assumption, taking
for granted what really needs to be accomplished and supported by
its specification.
The requirement under Subsection 34.(1)(b) is that the
specification present the invention in such clear, exact and
concise terms as to enable one of ordinary skill in the art to
make and use the invention with the same success as the inventor.
In R.C..A Photophone, Ld. v Gaumont-British Picture Corporation,
Ld and British Acoustic Films, Ld. (1936) 53 R.P.C. 167, Lord
Justice Romer stated, at page 195, that:
. . . It is the duty of a patentee by his claim to make quite clear what is the ambit
of his monopoly in order that workers in the art may be left in no doubt as to the
territory that is forbidden them during the life of the patent. If he fails to do this,
his patent becomes a public nuisance. It is equally incumbent upon him to
describe at least one way, and the best way known to him, of carrying his invention
into effect, in order that, when his monopoly comes to an end, the workers in the
art may turn the invention to account. This is the consideration he pays for his
monopoly.
The Applicant has argued that it was standard procedure to
prepare hybridomas and monoclonal antibodies for antigens at the
date of filing the application. This argument was developed by
the Applicant in its response of April 8, 1994, at page 18, as
follows:
The fundamental aspect of the invention is, as the Examiner has stated in the final
action, the HIV-2 virus and its antigens. Once the antigens have bees identified
and characterized, it is submitted that:
(1) the path to the preparation of the monoclonal antibodies is an easy one for
those skilled in the art, and
(2) the resulting antibodies will have the desired immunogenic character.
As stated at page 50 of the specification, to produce antibodies, an
immunogenic substance (such as an HIV-2 antigen) is injected to an animal (usually
a rabbit, a guinea pig or a sheep) to produce polyclonal antibodies. Monoclonal
antibodies can then by [sic] produced using traditional techniques. What
constituted a traditional technique for producing monoclonal antibodies as of
Applicant's priority date of January 22, 1986? For example, lymphocyte cells
from the immunized animals producing antibodies to the injected immunogen are
fused to myeloma cells. The resulting hybrid cells are inoculated in the peritoneal
cavity of syngeneic hosts. This results in the formation of tumors (hybridomas)
that secrete high concentrations of monoclonal antibodies in the sera or ascites
fluids. Such technique was well-known to the person skilled in the art way before
the priority date of January 22, 1986 as it is demonstrated below.
The Applicant then presented a brief review of the state of the
art in preparing hybridomas and monoclonal antibodies starting
with the work of Kohler and Milstein in 1975.
The Board acknowledges that methods of making monoclonal
antibodies to various antigens were known in the art at this
date; however applying these methods to a new antigen constitutes
a new process requiring a new protocol to produce the secreting
hybridomas and novel monoclonal antibodies specific to the
antigen.
James W. Goding, in "Antibody Production By Hybridomas", Journal
of Immunological Methods, Volume 39, page 286 (1980) comments on
the nature of this type of work as follows:
. . . It should be stressed that the production, testing, cloning and characterisation
of monoclonal antibodies is not a trivial procedure. It should not be undertaken
without an appreciation that it will involve some months of fairly continuous bench
work.
To understand the general concept of the physiology and the
biochemistry of antigens, antibodies. hybridomas and monoclonal
antibodies, the following is an outline from the book Monoclonal
Antibodies by Karol Sikora & Howard M. Smedley, 1984 published by
Blackwell Scientific Publications, page 3:
Many molecules are capable of giving rise to an immune response, i.e. they are
antigens. Each molecule has a unique shape. It is this shape which gives rise to the
specificity of an antigen-antibody reaction. Clearly larger and more complex
molecules may have several different regions, each of which is capable of
accommodating an antibody. Such regions are known as antigenic determinants or
epitopes. It is possible for one antigenic molecule to contain several epitopes.
Smaller antigens, on the other hand, may possess only one epitope. The basis of
the antibody-antigen interaction is the fitting together of two molecules of
complementary shape. The shape of the antigen is determined by the three
dimensional structure of the molecule. All immunoglobulin molecules [antibodies]
have a similar basic structure consisting of two heavy and two light chains held
together by disulphide bonds.
(An antigenic epitope fits and binds at the binding site between
the N terminal of a pair of a light and a heavy chains.)
On page 8, the authors continue:
Although the fusion techniques outlined above enable antibodies of defined
specificity to be produced in endless quantities, it should be stressed right from the
beginning that for every successful antibody which is produced many failed fusions
or irrelevant monoclonals will be produced. Many hours of laboratory time are
spent to produce a single useful MCA [monoclonal antibody]. Some of the
reasons for this are obvious. First of all the definition of what is a "good"
monoclonal antibody is arbitrary and depends upon what function is required of it
by the investigator. . . . It is therefore important for an investigator to know what
he requires of his antibody before deciding which antibodies are good or bad.
Further, many antigens against which the investigator is attempting to raise
monoclonal antibodies are only weakly immunogenic. The animal's immune
system therefore responds poorly to the immunogen and so the incidence of
suitable monoclonals is low, thus increasing the workload.
The state of the art at the approximate time of filing the
application (1987) can also be estimated from Goding in his book
Monoclonal Antibodies: Principles and Practice, Second edition,
1986, Academic Press. On page 281, in writing about the creation
of conventional [polyclonal] antibodies the author states:
The production of monoclonal antibodies involves a great deal of work. A
suitable screening assay must be developed before the fusion, and hundreds or
thousands of tests will have to be performed before the prized clone is
immortalized. The sheer work and time involved in "cell farming" is considerable.
In comparison, the preparation of antibodies with nothing more than antigen, a
rabbit, and a syringe, might be seen as a technological breakthrough! For many
purposes, conventional antibodies will do the job adequately, with much less work.
On page 3, Goding explains:
It would be wrong to think that monoclonal antibodies will completely
replace conventional serology. The production of monoclonal antibodies involves a
great deal of work, and a high level of commitment. There will often be occasions
when the effort required may not be justified. Fortunately, a wide range of
monoclonal antibodies is becoming commercially available.
. . . I have also tried to point out areas in which the literature gives misleading
impressions, and a few situations in which published procedures are unreliable.
. . Immunochemistry also has an oral tradition, and a surprising number of key
elements are not easily accessible from the literature. I have incorporated some of
the elements where appropriate; in many cases no citation is possible.
On page 59, in the Chapter titled "Production of Monoclonal
Antibodies", Goding adds:
Although the technology of hybridoma production is now firmly
established, there are a large number of steps involved, and each of these may be
carried out in many different ways. The diversity of published approaches reflects
both individual biological problems and previous experience. The methods also
vary in convenience, speed, reliability and expense, but there is no one "right"
approach, and ultimately each investigator must choose and adapt the published
strategies to individual needs. An appreciation of the variables and compromises
will help minimize the effort required.
It is clear from the above remarks by Goding that a person
skilled in the art must establish a specific protocol to produce
the hybridomas and the monoclonal antibodies for each of the
antigens. In exercising his skill, the expert would not depend
entirely on the articles and textbooks in the field or
"traditional techniques", as a number of key elements are not
easily accessible from the literature. If the preparation of
monoclonal antibodies to antigens were routine and predictable,
then all monoclonal antibodies to antigens would be obvious, and
the field of immunology would routinely produce all kinds of
cures. This is certainly not the case.
The Board agrees with the U.S. decision in Ex Parte Old 229 USPQ
197 (Bd. Pat. App. 1985) which states, on page 200, that:
. . . Although the technique underlying hybridoma technology is well recognized,
nevertheless, the results obtained by its use clearly are unpredictable. Hybridoma
technology is an empirical art in which the routineer is unable to foresee what
particular antibodies will be produced and which specific surface antigen
recognized by them. Only by actually carrying out the requisite steps can the
nature of the monoclonal antibodies be determined and ascertained; no "expected"
results can thus be said to be present.
The Applicant submitted two published papers during the oral
hearing, namely: "Two Neutralizing Domains in the V3 Region is
the Envelope Glycoprotein gp125 of HIV Type 2", by Ewa Bj”rling
et al., published by The American Association Of Immunologists in
1994; and "Multiple Antigenic Epitopes Expressed on gag Proteins,
p26 and p15, of a Human Immunodeficiency Virus (HIV) Type 2 as
Defined with a Library of Monoclonal Antibodies", by Hiroyoshi
Komatsu et al. which was published in 1990 in Aids Research and
Human Retroviruses, Volume 6, Number 7, by Mary Ann Liebert,
Inc., Publishers. The Applicant argues that these papers
disclose the preparation of monoclonal antibodies using the
subject antigens and this fact proves that preparing the
hybridoma and monoclonal antibodies are a standard procedure such
that claims 84 and 85 cannot be rejected for lack of disclosure.
It is the Board's opinion that the Applicant cannot rely on post-
filing work by others to support its claims. The Board agrees
with the U.S. decision in Re Glass, 181 USPQ 31 (C.C.P.A. 1974)
that sufficiency of support is measured as of the date the
application is filed, and that post-filing publications cannot be
used to fill in what is missing from the teaching of how to make
and use the claimed invention. Furthermore, the Board concurs
with the U.S. decision in Gould v. Quigg, 3 USPQ2d 1302 (Fed.
Cir. 1987) that post-filing publications may be used to show that
the invention, as described in the application when filed, was
operable.
In a further argument, the Applicant urged the Board to follow,
by analogy, the practice followed in the chemical arts. Thus at
page 23 of the response dated April 8, 1994 it is stated that:
In a patent application disclosing an invention in the chemical arts, an
applicant usually provides general comments on the type of compounds of interest
with specific examples to compounds belonging to the generic class. This
Applicant may describe a way in which derivatives or other embodiments which
might be quite different from the specific compounds disclosed can be prepared.
Claims to these compounds are usually added and allowed by the Patent .
This type of situation is perfectly in line with the decision of the Supreme Court of
Canada in Monsanto v. the Commissioner of Patents (1979 2CPR 2d 161) in
which Mr. Justice Pigeon made the following comments
:
"In my opinion, the Commissioner cannot refuse a patent because the
inventor has not fully tested and proved it in all its claimed application.
This is what he has done in this case by refusing to allow claims 9 and 16
unless restrictive to what had been tested and proved before the application
was filed. If the inventors have claimed more than what then have invented
in included substances which are devoid of utility, the claims will be open to
attack. But in order to succeed, such attack will have to be supported by
evidence of lack of utility. At present, there is no such evidence and there
is no evidence that the production for utility of every compound named is
not sound? [sic] and reasonable. "
and at page 25 :
According to the Supreme Court in the Monsanto decision referred to above (c.f.
supra), a "sound-prediction" is based on the capacity of the person skilled in the
art to foresee the properties of a claimed product. Applicant has demonstrated
that techniques to produce monoclonal antibodies have become tools generally
available to a person skilled in the art of hybridoma technology, in the same way
the preparation of specific chemical compounds from a generic formula based on
known processes is available to the person skilled in the art of chemical synthesis.
In the Monsanto case referred to by the Applicant the application
disclosed a class of chemical compounds which inhibit the
premature vulcanization of diene rubbers. The inventors gave the
common formula for the nucleus of the substances and described
various radicals which could be used in the class. Three
representative compounds were disclosed, but many more compounds
were not disclosed yet were claimed. The specification described
the preparation of the three compounds specifically, while the
preparation of the other compounds was described generally by
formula.
It was recognized in Monsanto's application that the disclosure
provided sufficient direction to enable a skilled chemist to
prepare the compounds using methods previously known in the art
but it was determined that since the inventor had not prepared
and tested all of the claimed compounds it could not be fairly
said that the inventor had invented all of the claimed compounds.
The rejected claims were however later found allowable by the
Supreme Court on the grounds that there was no evidence that
either the compounds not prepared or tested would not work in
view of the disclosed examples of compounds prepared and tested.
Thus in Monsanto 42 C.P.R. (2d) 161 the Supreme Court, at page
175, referred to the judgment in Olin Mathieson Chemical Corp. v.
Biorex Laboratories Ltd. [1970] R.P.C. 157. In Olin Mathieson,
the patent covered trifluoromethyl-phenothiazine and a number of
related compounds, of which a small number only had been tested.
The question was then whether the inventor ought to be limited to
the actual substances which he had tested. On page 193, Mr.
Justice Graham defined sound prediction as follows:
Where, then, is the line to be drawn between a claim which goes beyond the
consideration and one which equiparates with it? In my judgment this line was
drawn properly by Sir Lionel when he very helpfully stated in the words quoted
above that it depended upon whether or not it was possible to make a sound
prediction. If it is possible for the patentee to make a sound prediction and to
frame a claim which does not go beyond the limits within which the prediction
remains sound, then he is entitled to do so. Of course, in so doing he takes the
risk that a defendant may be able to show that his prediction is unsound or that
some bodies falling within the words he has used have no utility or are old or
obvious or that some promise he has made in his specification is false in a material
respect; but if, when attacked, he survives this risk successfully, then his claim does
not go beyond the consideration given by his disclosure, his claim is fairly based on
such disclosure in these respects, and is valid.
(Emphasis added)
In the present case, the Applicant does not show by examples or
broad statements the steps that were successfully used to produce
hybridomas secreting monoclonal antibodies which are capable of
binding only with the specific antigen. Had any hybridoma and
monoclonal antibody for certain antigens been prepared, then it
would have been arguable that other hybridomas and monoclonal
antibodies, which were claimed but unprepared or prepared but
untested, could be allowable in view of the "sound prediction"
principle. In this case there is no consideration given by the
disclosure to any monoclonal antibody so that there is nothing
upon which to base a sound prediction.
The Board finds that there is a lack of guidance in describing
the core method to be used and the permissible modifications of
that basic method for the specific antigens disclosed. Such
deficiencies in guidance cannot be remedied by referring the
person skilled in the art to experiment with the "traditional
techniques."
In summary, the Board also finds that the description does not
include any clear references or description to enable the person
skilled in the art to make and use the invention without
considerable and protracted experimentation. The Board concludes
that the hybridomas and the monoclonal antibodies embraced by the
claims 84 and 85 are not described or enabled by the present
disclosure as required under Subsection 34(1) of the Patent Act.
Accordingly the Board recommends that the Examiner's refusal of
claims 84 and 85 be upheld.
Peter J. Davies Effat Maher Michael Howarth
Acting Chairman Member Member
I concur with the findings and recommendations of the Board. I am
satisfied that the Applicant is not by law entitled to be granted
a patent containing claims 84 and 85 and I therefore refuse to
grant a patent containing these claims on this application.
M. Leesti
Commissioner of Patents
Dated at Hull, Quebec
this 11th day of December 1995