*1 patentability question of obvi- inventions made ous modifications be determined is now to coworkers standards, statutory reference identity reference assignee. me seems to It therefore remove impact these decisions anomaly law. from the argued may effect that the While it encourage will be to
of these decisions filing applications on basic in-
delay in allow coworkers time in order to
ventions modifications obvious
to discover may patented, I do not feel this also be problem. The will become a substantial Schulte, Norwich, Bernard Y. J. N. may applicant possible penalties which an (Thomas Thomas, Thomas, & Edwin M. charge of of dili- lack suffer because of a Ralph Thomas, Arlington, Va., L. gence suppression of his or of invention counsel), appellant. safeguard against adequate provide an Joseph Schimmel, Washington, delay. D. C. (Joseph Nakamura, Washington, F. D. C., counsel), for the Commissioner
Patents. Judge, WORLEY, Before Chief RICH, ALMOND, Judges. SMITH and ALMOND, Judge. appeal
This is an from the decision of Application of Warren Francis CAREY. United States Rehearing Denied June and Patent April Appeal No. Court Customs 25, Appeals. 1968. 7923. 20, 1968. titled in the claim: firming terial The invention is Patent claim of 6. The method of “Urological Compositions.”1 Office Board of rejection appellant’s application tract infection in a host adequately of the sole remain- combating Appeals described bac- en- af- subject comprises orally thereto which administering host in said mg. unit about form about 100 to (5-nitrof urylideneamino) of 1- -2-imi- dazolidone.
The references relied are: 2,746,960 (Gever) May et Gever al. (Mintzer), Mintzer et al. Antibiotics 2, Chemotherapy, Vol. No. Janu- ary 1953, pages 151-157. (Paul) Paul et al. Antibiotics and May Chemotherapy, No. Vol. 1960, pages 287-302. 259,403 February 18,
1. No. Serial filed 1963. *2 rejected unpat relationship tural re nitrofuran Claim 6 stands (designated appellant’s Paul claim considered with cited entable over Gever NF-246) 103 on the herein as and nitrofurantoin and Mintzer under 35 U.S.C. § (NF-153),2 urinary ground the close struc known tract in view of well antibacterial, range peutic equally it would be obvious that levels wide proper- hosts, possess regard inquiries similar NF-246 would has led to NF-153, disposition physiological and its use in treat- ties of these urinary compounds. tract infections would be ment of patent discloses and obvious. The Gever NF-246, compares Paul NF-153 and compound the nitrofuran NF- claims aas among compari- other nitrofurans. This patent The further 246 here involved. compounds son have low shows both compound is effective discloses that this blood and fecal It also concentrations. gram against by caused infections both NF-153, shows that when administered organisms gram negative positive and dosage mg./Kg. body in a level of 25 surprisingly toxic- and has a low level of urine, weight, in the excreted 52% orally ity when administered. while administered in a Mintzer discusses the use NF-153 mg./Kg., level of excreted 10% urinary tract infections. the treatment the urine. prac- According Mintzer, NF-153 rejection expressed The his examiner by body, tically completely absorbed as follows: concentration, as evidenced low fecal in the urine to about is excreted (1) of the facts that dosage given, bactericidal has combatting urinary tract in- is useful urinary below concentrations levels structurally fections, (2) NF-246 is against organisms com- tested vitro (3) closely related to monly implicated tract infec- possesses qualities the same reports tions. The article clinical studies being responsi- which are indicated as of this effectiveness ble the success NF-153 as having treatment antiseptic, tract is believed organ- infections caused tract various ordinary in the that one of skill isms. logical would consider it was study The Paul article directed to a high degree anticipate prob- with a of the distribution of certain nitrofurans ability a trial of NF-246 as a uri- body. purpose The reason for nary antiseptic would be success- study is stated the authors: Thus, appellant’s pre- ful. invention is spectrum of com- The effective these sumed obvious. variety pounds a wide invading microorganisms, ap- rejection and the attacks the on sev- grounds. parent toxicity He lack of at chemothera- eral first asserts that since compounds
2. The structures these two are: (NF-246) (NF-153) assignee application me con- would not convince of this had values urinary tract on of NF-246 as a research work trial ducted considerable hope any could better than have and NF-246 from both NF-153 suggestion of its use as success. 1959 with no appellant’s until antibiotic expert opinion of an February *3 application filed in was question art on the of obviousness evidence of un- this should taken as be only is of evidence an invention one bit dispose this obviousness. We can along other to be considered with evi argument noting rejection is the that record, including prior the dence the upon a of com- obviousness view based Weber, In re art. references, one of which bination of three opinion of board makes The the 1015. May published until 1960. We was not summarily it clear that the did not board record does not further note that this affidavit, the it dismiss but did consider invention made his show when lacking persuasive found effect. and it record, —for we can discern from all findWe no error here. contemporane- it could have ously made been argued Appellant that he has has also discovery of NF-246 with unexpected surprising results shown and Gever. NF-246, in the use of based argues Appellant that no citation also Regan of the That affidavit. equiv- has alency advanced to establish been reports on the affidavit clinical tests carbonyl methylene groups. and treatment of tract infections necessary since He feels citation is patients. human The board was unim- group of one for the other a substitution affidavit, noting pressed it this that is the between NF-153 sole difference reports patients that of treated with and think this statement NF-246. We drug, 21 were unsuc- courses point. ques- of the misses the The issue only The cessful. board also noted that tion before us is not obviousness good 8 of 24 daily dosage had at a results substituting carbonyl; methylene for a mgm, of 200 that already ques- Gever had done that. Our investigators mainly seem have been to tion is would be obvious to whether impressed toxicity with the lack of application particular substitute in this NF-246, already a characteristic noted methylene compound having one by Gever. carbonyl compound group hav- for Appellant criticizes board for fail- ing carbonyl groups in two view of recognize reported to that clinical secondary teachings reference of certain run, customary studes as is physiological and antibacterial similari- investigations, drug most initial at dos- ties between two. ages well below the recommended levels. argues argues the examiner Appellant dosage that at even this give proper level, and the board weight to failed y2 which the recom- to% by Mary to NF-153, good affidavit filed Dr. mended Paul, one of the authors of the Paul ref- were obtained in of the cases. He argues erence. This good affidavit discussed the surprisingly this to be a re- showings record, sult, factual particularly since NF-246 is ex- then concluded: creted the urine at far lower levels than NF-153. presented From data there I would degree expect, high prob- not with a arguments The appellant’s trouble ability, point that a they require trial of NF-246 as on this is that us to guess success- be what effect NF-153 would have * * * y2
ful. On their face these the recommended level. It % Company, ele, sponsor 3. The Norwich Pharmacal which of the authors of the assignee reference, is also of the Gever Mintzer article. employer of the of the Paul authors arti- of a the new use process involves ref- performance of the only pat- may composition of matter known condi- compound under similar erence provided pos- other conditions ented it becomes is established tions patentability are satisfied. performance of the compare the sible improved or show position claimed The Patent Office From all unexpected results. relationship that, close affidavit, may have NF-246 involved, shown it would chemical structures in these grossly inferior to compound, appellant’s been be obvious tests. particular clinical possess same would also nitrofurantoin, appear Regan does organisms antibacterial. well-known several establish Considering prima facie to NF-246 but sensitive establishing obviousness, it seems me However, since vitro. conducted tests *4 by the prima facie case is rebutted this method of com- is a claimed invention the appellant. developed It is the urinary record bating infections tract bacterial de- inadequate reverse on this basis that I would host, the is an in this a of the comparative cision board. in vivo tests. for substitute in agree similarities chemical Structural the examiner that We provide compounds, homology, art, knowing prior the like in the of the skilled ready orally chemist a tool for classifica- an administered use of NF-246 as continuing having spec- provides a agent tion. This fact a broad antibacterial temptation including activity, a chemical classi- convert trum of antibacterial legal e., coli, presumption, against fication into i. a E. identified given organism that since all chemicals of class in as one causitive Mintzer properties knowing infections, have certain common there tract of the “legal presumption” toxicity one would be ex- and substantial low legally knowing in of the other. obvious and cretion of fallacy the court striking similarity This has been before structural predi- guises frequently different known tract antibacterial de- expect on a doctrinal extension our to have cated would Henze, combating urinary utility cision in In re infec- However, (1950). we nothing as CCPA 1009 There is in the affidavits tions. Mills, pointed F.2d out in In persuades which us (1960), the Henze unexpected achieved in view of supports authority is not which prior case art. presumption. pointed out such a As we The decision of the board is therefore Mills, 1190: 281 at id. at affirmed. “presumption unpatent- The term Affirmed. ability,” case, it Henze is used belief that reversal of the decision of SMITH, majority, dissenting from Judge (dissenting). I do so because it is facts of the conclusion of record board. require my note omitted.] plicants refers to an inference of fact. a considerable [******] In the Henze length case, the observed this safeguard court went to tendency [Foot- ap- Appellant’s legal position predicated here is of the freeze into Patent Office to discovery upon admittedly general application what, his that an rules compound, designated NF-246, best, applicable par- known are statements effectively used, orally Thus, could be when ad- ticular fact situations. host, “presumption unpatentability” ministered unit form to a re- case, to combat bacterial infec- ferred in the Henze was lim- composi- tions. His thus based ited to a claim directed 100(b) provides (a compound), 35 U.S.C. which that a tion of matter new § system adjacent homologue old as simi- as well which was differences properties reactions larities art. given any homolo- the members of “pre- this how pointing out After gous series. ap- on the placed burden sumption” sug- chemist, A and it from stand- even Henze] plicant, [in court point skilled this art a chemist which types of evidence gested certain question must obviousness overcome produce to applicant could resolved, be consider the differ- would further evidentiary burden types limiting ences as well the similarities in itself with concerned properties mem- and reactions of the called be proofs could which given homologous any bers series. said: Patent Office * * * should, per Homology se every not mean does This therefore, be treated a chemist justi- would Office it, being nothing more treat exacting empirical data fied than a which must be considered fact applicant respecting the other ar- with all before relevant facts homologue un- tested prior art riving at the conclusion of “obvious- limitations conditions the same der specified ness” in 35 U.S.C. 103. § com- for the claimed forth set as are argues that reference to the old reaction pound where al., NF-246 in et Gever ais those conditions compound under *5 admittedly teaches that NF-246 has a cog- general fact of established well spectrum activity * * * wide anti-microbial [37 art. in nizance the orally administered, and can be not does 201, 1015, 85 at 181 F.2d at CCPA suggest urinary the USPQ 265.] at compound. support He factual relies for further stated: Henze] court [in The position on the Dr. affidavit of pat- Mary rebutting Paul not refused a as the examiner’s was The position, only placed un- error and asserts in the but was treat- ent in limine ment requirement over- to accorded Paul affidavit reasonable der a reasonably The raised Office. Paul presumption affidavit con- come reasonably ex- tains a relevant he could and which factual * * legal basis from The Patent which can we draw a pected *. to meet. Weber, representative conclusion. In See public’s 341 F.2d as Office 143, right require (1965); evidence 52 CCPA 1015 In re to Chi- has lowsky, 908, to dissolve as 50 CCPA is suitable of invention (1962). unpatentability aris- presumption of subject ing the nature of out of It is noted that neither the examiner raising the criteria matter where challenged nor the quali- board Dr. Paul’s here, are of universal presumption, as fications in this art. She states she in acceptance those skilled was familiar with each of the references ** * at [37 involved. upon support rejection. relied to USPQ at F.2d at particular, publi- she commented on her 265.] (a “prior cation art” reference appellant’s claims) considered, simi- the structural Thus follows: compounds and larities The publication, Paul et al. some legal give is- rise to the same years subsequent to the Gever et al. homologous as did existence sues patent dealing with new chemical com- we As compounds Mills case. pounds including NF-246 and the stated, 281 F.2d at there publication Mintzer et dealing al. at 1191: investigation an nitrofurantoin, * ** presents Homology provides physiological for the data on the dis- system variety of struc- and convenient distribution of a chemist in that Inherent nitrofurans when classification. tural administered to opinion of an ex- as the to consideration laboratory These data animals. specific data predicated factual pert on (I-VII). of Tables in a series tabulated portions of those digest there indicated in represent then avail- They underlined. level, have been uri- the affidavit which of blood determinations able to referred excretion, plasma differences excretion, factual nary fecal water milk, indicate that solu- Dr. Paul bili- binding, protein excretion properties bility excretion and presence cerebro- ary excretion, with the com- are inconsistent degradation of NF-246 spinal fluid, tissue and parable properties Those of NF-153. affording to those nitrofurans, certain properties provide a factual inconsistent appreciation their interested reached to the conclusion rebuttal disposition distribu- physiological from inferences examiner board tion. predicated chemical on similarities commentary on In the Thus, compounds. the two structures of involved the nitrofurans excretion of feel I the board and the examiner erred referring pages and 294 and giving proper weight Paul not among noted I Table rebutting the inferential urinary excretion varied nitrofurans prima facie of obviousness little or none dose from 75% they relied. species The influence of administered. Appellant properly points out that the noted, also nitrofurantoin maintain- significance of the structural similarities rat, dog excretion compounds on between conclusive nitrofuran, man ni- but another He issue of obviousness. states: droxyzone, in rats dwindles 25% * * * dogs slight seemingly in man. Other That varia- 6% particular in- remarks nitrofurans tions in chemical can result structures biological clude reference to secretion of in marked differences them, NF-189, by present renal tubules illustrated *6 any sensitivity by comparison absence of amount substantial of the a There organisms furazolidone in urine. of certain strains or to NF- any lacking particu- sensitivity no further reference to 246 while NF- to (Table lar nitrofuran. 153 4 of Attachments filed with ** Regan *) Affidavit of I Table lists a series of nitrofurans urinary the marked difference in ex- plasmas and the determination rate, cretion for while 52% levels, urinary excretion con- and fecal ** only for NF-246 *. 10% centration thereof when administered Regan orally present- affidavit of to Dr. John Ward From data rats. also was submitted expect, I to show ed there would with a treating high degree effectiveness NF-246 in probability, that a trial urinary agent tract ar- infection. urinary of NF-246 aas gues together affidavit, that this with comparison would be successful. In to supportive studies, shows NF-246 to nitrofurantoin, solubility its water against greater range be (88 190); effective a plasma lower its level vs. organisms bacterial NF-153 (lf.7 2.6); than and to greater, somewhat its vs. exhibit a lesser urinary incidence of mani- toxic considerably excretion lower festations. (10 52) vs. and its concentration fecal (0.1 2.0). considerably less vs. On The examiner dismissed affidavit their face these values not con- would failing for improve- its to show vince me that a trial of NF-246 as a ment over NF-153 as to overcome the urinary agent any could have presumption of He obviousness. dis- hope better than of success. [Em- missed the of effectiveness phasis added.] against greater range a or- bacterial ganisms While some of Dr. Paul’s affidavit based vitro on test opinion, a statement of her it is entitled rather than on an in test and vivo there-
«52 mg. only per day (one it not definitive. He failed- fore found received vitro, mg.). compares test was in note This with to that while dosage prior recommended art nevertheless conducted was mg. day
organisms per urine of those NF-153 at 400 found in the participating in treatment of severe infections. Table patients the clinical Regan study. affidavit shows that the respond to had an who failed Further, to in vitro tests seem me average age of about had 75 and most comparison of have been direct to undergone prostatectomys. and NF-246 on 'effects of both urges Appellant strongly organisms the urine found in organ- Regan properties for patients. Twenty does show clinical surprising and in- NF-246 which are both isms were to NF-246 and sensitive teachings in unexpected only NF-153 while sensitive prior art. One skilled insensitive sensitive NF-153 and tual have were in studies Isaacs, NF-246. This ism. (1965): likely determine which author, [*] Appellant avers that the board erred *7 must be has pharmacologically both the examiner and the board * to find order to evidence of in The examiner and the board seem failing conclusions which Dr. [*] ** ignored run, them. been appellants reported is the [*] eradicate the none which secure cited and we proved One recognize the in are most initial As standard vivo test, should pointed thing tests. No vitro patent, utility active as noted offending requires that the clinical in Regan would be most have have seems tests and fac out in vivo Regan only submitted investiga- substance been able authority testing. way to organ- draws clear: of a felt the would not where the examiner as consideration the urinary tract antibacterial NF-153. tics periment mended for ranged would not antibacterial assuming even more high antibacterial urine tered urinary Mintzer et Similarly, (3) (1) 10% low of a a 50% low blood excretion of the from about orally good (45% expect tract antibacterial or less of surprising expect to majority Mintzer et describing four characteris- NF-153. al., my view, excretion. NF-246 in spectrum. of administered found in the level; excretion decided leading urinary tract % tact antibacterial: find excretion for if one takes These al. is compound in the amount disadvantage of y2 to be useful However, (4) cited did feces; (2) in view led 60% compared area,1 he adminis- a broad not dis- recom- dose); by the to ex- levels even cure into dosages properties drugs, close four cri- tions on new that these were at be- far good urinary teria of a tract antibac- low the recommended levels. urges Rather, reported terial. good these were a that the criteria show results, e., sterility previously i. mere statement of in 18 urine patients (60%) receiving investi- out disclosed gations Eaton Laboratories 30 drug. by appel- The fol- animals. This is considered lowing paragraph reference, outstanding, especially lant to be how- if one ever, appellant urges, (40%) notes that to me 12 seems who aptly improvement property failed to indicate more of NF- were show receiv- - ; (1967) Tomlinson, 1. The court its F.2d has often stated basic dis 363 agreement 928, ; try (1966) 1421 -with an “obvious 53 CCPA In re analysis” Huellmantel, under 324 F.2d 51 § 35 U.S.C. 103. See CCPA Lindell, (1963). In re 845 investigating the use aas he states 153 which pH in per its urine Since the urine can apparent maximum of about 20 : vitro, cc. interested concentration during therapy, these antibacterial reach mg. per results seem Mintzer of this at least 40 of Furadantin solubility in et al. wherein spite of cc. para- mg. Application of John V. HARRINGTON Application of Detlef WINKELMANN. United States Court and Patent Henning Appeal April 25, 1968. Nos. H. Borchers. Appeals. Customs 8160. to the fact due This is doxical. large of Furadantin amount vitro blood at the urine dissolved 7.5, glomerular pH reduction precipi- produce pH to 5.5 does supersatura- A state of stable
tation. coupled phenomenon, exists. This tion extremely low blood levels crystalluria suggests drug, no of this feared use
need be sup- preparation. conclusion This
ported our clinical observations. pri-
Thus, it et al. seems Mintzer high
marily interested (NF-153), of Furadantin
concentrations which exceeded
i. e. concentrations
solubility in still in a urine but existed Thus, supersaturation.
state stable argues phenom- it that was this prime these
enon which was of interest
investigators exactly is in ap-
property in NF-246 differs so
preciably from vs. 52% 10% evidenced I et al. Table of the Paul appellant’s It
reference. contention if one had en- skilled possible
visioned reading al. of Mintzer et discourage use envisioned compound. appellant’s It is also discovery *8 for NF-246 both un-
expected surprising relatively low excretion. de- factual base
veloped my opinion below is of such strength prima overcome facie infer- Patent Office based on
ences drawn from the the examiner teachings my opin-
naked of the art.
ion reasons are reverse sufficient decision board.