I. J. FELLNER New York, New
I
York
NVENTORS and their attorneys have allegedly met of late with some discouraging difficulties in obtaining adequate patent protection for organic compounds. From numerous objections raised against this type of invention they draw the conclusion that the Patent Office, its tribunals, and some Federal Courts have adopted a new, more rigid, and frequently even inconsistent standard in evaluating novelty and inventiveness of organic substances. The obiect of this paper is not an academic discussion on the-soundness of the legal principles as applied and presented by the Patent Office, but rather a practical analysis of its more recent decisions and opinions by way of illustratious to guide us in a reasonable estimate of the value of patent applications with regard to their prosnective allowance. Organic compounds are patentably classified under the comprehensive term of "compositions of matter," but for the purpose of our study we will limit this term to the-gr;up of unitary structural entities of either a generic or a specifically defined configuration to the exclusion of physical mixtures or combinations in a chemically unreacted state. To be patentable, an organic compound must be new, inventive, and useful. Novelty and invention are interrelated criteria in that the height of the invention is measured by the state of the prior art. The gist of the invention may reside in the novelty of concept or of properties. Usefulness is an ancillary prerequisite and must be apparent and so indicated. Inherent or potential usefulness is not sufficient. The argument that every new organic compound, irrespective of its practical value, advances the art by enriching it with a new product is no longer accepted; therefore, claims for new chemical compounds will not be granted as a matter of course. Among the manifold grounds of rejections employed by the Patent Office, the novelty of a compound is challenged because it represents merely an aggregation of known constituents or a substitution of groups within a homologous series of adjacent members whose con6gurative concept and chemical properties are easy to interpolate. In other cases rejections are based on a mere change of degree, lack of usefulness or unexpected qualities, or again on the ground of undue breadth of a claim. One of the fundamental considerations in appraising inventive dignity of a chemical invention is the element of predictability, and modern practice frequently
relies in this respect on the now almost classical rule of In Re Wietzel, or the "noninventive testing rule," (39 F ( 2 ) , 669, 1930), where the following situation arose. The applicant claimed a novel process of producing a mixture of formamide and hydrocyanic acid by treating an alkyl formate with ammonia in the presence of a dehydrating catalyst. The involved reaction may be illustrated by the following equations:
*"",."
D"t-6
+
L
HCO-OR NHI = ROH HCO-NH1 z2 HCN
++ HCO-NHn H20
The prior art disclosed the preparation of higher amides and nitriles by treating higher aliphatic esters with ammonia, also in the presence of dehydrating agent, as represented by the following: Reference RCO-OR' NHZ = R'OH RCO-NH* RCO-NHX ~3RCN HZO
+
++
The Patent Office, considering hydrocyanic acid as the nitrile of formic acid, rejected the claims on the ground of close analogy between the two reactions. The applicant contended unpredictability of the claimed process in view of the fact that first members of a homologous series frequently display an atypical behavior with unforeseeable results and that this applied to formic acid as the head member of the fatty acid series. He further contested the hypothetical identification of hydrocyanic acid with the nitrile of formic acid. The Court of Customs and Patent Appeals, affirming the lower court of the Patent Office, formulated the following rule: And where there is no real reason to suppose that the result would not be produced, there is no invention in trying it and finding out that the process is successful.
This noninventive testing rule has been repeatedly quoted and interpreted and extensive comments thereon are found in the literature of Patent Jurisprudence. An interesting case involving the issue of inventiveness in view of substitution is presented in the decision of I n Re Christmann (43 USPQ 415, 1939). The invention related to an insecticidal composition including a reaction product of hydrofluosilicic acid and a guanidine. The basic guanidine constituent was intended to function as a repellent while the anionic hydrofluosilicic acid acted as ,toxic ingredient. The prior art showed (1) the moth moo fin^ pro~erties of manidine compounds, (2) the mothprboing properties of guanidine Presented before the Division of Chemical Education at the acids, (3) a wide variety of reac109thmeetiilg of the American Chemical Saciety in Atlantic City, plus April S 1 2 , 1946. tion compounds of organic bases other than guanidine 555
-
-
with hydrofluosilicic acid, and (4) the insecticidal properties of fluosilicates. During the litigation the question arose: Was it invention to substitute guanidine for the old organic bases in fluosilicate combinations? Was it inventive to substitute hydrofluosilicic add for organic fatty acids in guanidine combinations? The Court of Customs and Patent Appeals said it was because the claimed compound was never conceived before and though guanidine, when standing alone, was known as having repelling qualities, no suggestion could be found in the prior art that it would retain such a characteristic when combined with hydrofluosilicic acid.' A similar situation was discussed in the case of I n Re de Groote (53 USPQ 354, 1942) where a patent was sought for a reaction product of blown castor oil and diethanolamine. The reference disclosed (1) a compound consisting of blown castor oil and tri-ethanolamine, (2) a compound consisting of unblown castor oil and di-ethanolamine, and (3) a statement that commercial tri-ethanolamine ordinarily wntains small amounts of di-ethanolamine. The Board of Appeals, referring to the aforementioned Wietzel doctrine, considered the claimed compound as a simple variation of features previously known which would suggestively fall withim the skill of a chemist without involving new or unobvious results. The Board was reversed by the Court of Customs and Patent Appeals which rather followed the aforesaid decision of Christmann and made the important statement that the ruling of Wietzel is only applicable to process claims when the resulting product is old in the chemical art. Where, however, a new product is in issue, the prevision rule of Wietzel is not pertinent. In Ex parle Reister (58 USPQ 620,1942) the invention related to water-soluble heterocyclic compounds of the type used as starting materials for thiocyanine dyes. They were obtained by introducing into an amino-substituted derivative of a heterocyclic ring a quaternary ammonium group by means of an amino group. For the sake of clarity we will illustrate the invention by one embodiment of the generic formula as follows:
'
-
A-NH-CO-CH~CI Pyzidine
H C . C ~
'1
+ HCI
The compound is formed by treating 2-methyl-6aminobenzofhiazol with chloroacetylchloiide whereby the chloroacetyl-2-methyl-benzothiazolamide(6) is obtained. The latter is then reacted with pyridiie
and yields the water-soluble quaternary ammonium thiocyanine of the configuration shown. One reference showed the preparation of strongly basic azo dyestuffs by treating amidated polyazodyes successively with chloroacetylchloride and a tertiary heterocyclic base, as for instance,
+
R-NH,
.
CI,CO-CH&I
+ HCI
= R-NE-CO-CHG1 AMIDE
AMIDATE? POLYAZODYE R-NE-CO-CH&I
CI BASIC Azo DyssTUaP
Another reference disclosed thiocyanins which had introduced into their molecules an amino group, as illustrated by the compound 2-methyl-6-amino-bemothiazol:
The examiner, in combining both references, concluded that it was obvious to replace R in R-NH2 by the benzothiazol and to react it with chloroacetylchloride and subsequently with pyridine to arrive a t applicant's configuration. In another publication the examiner had found the disclosure of hexamethylenetetraminium salts formed of monohalogenated acetylated aromatic amines and hexamethylene-tetramine, as for example: 7
7
A
'
CH*
CH.
In a following example there was s h o d a reaction product resulting from the combination of 6-chloroacetyl-aminoquinoline and hexamethylene-tetramine.
The examiner suggested that in this formula the hexamethylene group, being a tertiary amine, could apparently be substituted by a pyridiie and that the quinoline was replaceable by any other known cyanine intermediate, such as the well-known 2-methyl-6aminobenzothiazol. By this simple and allegedly obvious permutation of groups the applicant's formula could be conceived without the least inventive effort. The Board of Appeals, reversing the examiner, ruled it to be inadmissible to pick out groups of unrelated molecular assemblages and to combine them for the
purpose of anticipating claims when none of the references suggests the regrouping as a useful feature in a particular type of compound. The decisive criterion for anticipatory transmutation, therefore, is whether the identity of each of the references is destroyed by reassembling their various 'groups t o constitute the claimed compound. That this was done by the examiner in the instant case is evident. A similar pattern is presented in the case of Ex parte Burtner (67 USPQ 185,1944) where a patent was sought for antispasmodics in the form of basic esters of fluorene9-carboxylic acid, as exemplified by a piperidinium-4-01ester of the following configuration:
ing the controversid issue of configurative anticipation, allowed the use claim directed to antispasmodics in following the applicant's argument that in the field of drugs it is impossible to predict correctly the properties of chemical compounds without actual tests. In cases of homologous relationship the prognosis for allowance of a compound claim is much less favorable. An illustrative example is furnished by In Re Lincoln, (53 USPQ 40, 1942) where a claim for l-chloro-2aminopentane was rejected on final appeal by the Court of Customs and Patent Appeals. The controversial substance had the following formula : CHrCH1-CHTCH-CH2 AH2 Ll
The references were 1-chloro-2-amino-methylpropane, the next lower adjacent homolog,
and 2-N-diethylamino-1-chloropentane,
The examiner stated that from a purely chemical standpoint the concept of the formula showed no patentable novelty over a French patent disclosing 9fluorene-carboxylic acid esters of tropine and pseudotropine, such as illustrated. This statement was based H-C-OH HK/\CH~
H-C-OH
H-C-OH
H~C(\CH, H%C(\C&
The court, in this case, decided that the componnds of the prior art differed from the claimed product only by the presence and the position of an alkyl group, while the reactive groups giving the compounds their characteristics are the same and similarly positioned. In the absence of unexpected properties there is no invention involved in the new compound, as novelty alone does not constitute invention. The identical fate was suffered by an application for nitro-olehs in the case of In Re Hass and Susie, (60 USPQ 544, 1944), where claims were drawn to 2-nitro-propene, H
R-SUBSTITUTED 4-HY- OPEN-CAAIN TROPINE DROXYPIPERIDINOL TROPINE on the assumption, supported by Staudinger, that hydroxy-piperidinols may be considered as open-chain tropines if the pyrrolidine ring
I
NOz
I
H-C=C-CH1
and 2-nitro-2-hexene H NOS
I
I
HX-kc-CH,
The claims were rejected over one reference disclosing mono-nitro-dimethyl-ethylene, H NOz
is disregarded. No invention was allegedly involved in substituting piperidin-4-01 for the tropines in the French patent. The examiner further contended that in view of the known medical value of tropines, the identical usefulness of the claimed and closely related piperidinol ester was suggestively revealed by the prior art. The Appellate Tribunal, however, though evad-
I
I
Hd-C=C-CHI
and nitro-trimethyl-ethylene, 02N CHI
I
I
HsC-C=C-CHs
which is an isomer of 2-nitro-2-pentene.
The applicant contended that it ought not to be required to establish unexpected and unobvious properties or utilities not possessed by the previously known homologous and isomeric compounds. Claims to novel chemical products should be held to be patentable regardless of the prior art because such compounds tend substantially to promote the progress of science. The court, concurring with the examiner, pointed out that every chemist will recognize the same principal characteristics and physical properties in individual members varying from one to another in a homologous series and that the knowledge of the behavior of one of the members suggests to him the properties of the other members. I t so confirmed the ruling of the prior decisions that novelty alone did not establish invention. These two cases should be carefully compared with a recent decision rendered by the second Circuit Court of Appeals in Schering Cor9oration as. Gilbert, (68 USPQ 84, 1946). In this infringement suit a patent to Schering relating to poly-iodized derivatives of hydroxy-diphenylcarboxylic acids was attacked for lack of novelty. The litigious claim was drawn to beta-(4hydroxy-3,5-di-iodophenyl)-alpha-phenyl-propionicacid of the following configuration: CHrCH-COOHI
1
solubility factor
and the usefulness of the compound resided in its application as contrast medium in cholecystographic combinations where tetra-iodo-phenolphthalein was used theretofore:
The patentee relied on the advantageous combination of the solubility factor of the carboxylic group with the bile aPkity of the phenyl component and the opacity
of the iodine and referred to the harmful after-effects 'of toxicity in the phenolphthalein diagnosis. The defendant contended that the concept of the formula was predictable as a result of inevitable chemical reactions governed by the law of nature and that there was no novelty in the process used to produce that result. The court admitted the seemingly slight departure from the prior art structure, but emphasized that novelty and inventiveness must be evaluated not alone by the degree of change, but also in the light of the purpose sought to be accomplished. The particular configuration of the new molecule is but one of the millions of possible permutations in the rearrangement of atoms in the benzene ring. To elect the one that would impart to the new molecule the attributes which make it so uniquely acceptable as a contrast agent is sufficient evidence for inventiveness to support the validity of the claim. The interesting implication of this decision is that a new, though not inventive, compound may be patentable in view of its unexpected properties and utilities. In conclusion we may tentatively state the following rules governing the patentability of organic compounds: ( 1 ) If the compound is novel in its concept and/or its characteristics and unpredictable as to its possibility of existence, it may be patentable per se, and utility is an ancillary prerequisite of its patentability. (2) If the compound is new but not inventive in concept in view of isomeric or homologous relationship with prior art compounds, inventiveness may be supported by unexpected useful properties. ( 3 ) If the compound is old and claimed only for a new and useful application, it generally does not qualify as a patentable invention unless it is adapted in some manner for the new purpose. This rule has been established in the recent decision of In Re Thuau (57 USPQ 324, 1943). The apparent change of standards in the evaluation of inventiveness of organic compounds is not based on new judicial doctrines of the Patent Office and its tribunals, but rather constitutes a natural result of our more refined discernment as reflected by the rapid advance of the science of chemistry.
