*2 DAVIS, Before BALDWIN and ARCH- ER, Judges. Circuit DAVIS, Judge. Circuit appeal This is an from a final decision of the United States Patent and Trademark (PTO) Office Board Appeals of Patent (Board), sustaining Interferences rejec- through tion of claims 3 in the reexamina- application1 tion 3,428,- of U.S. Patent No. 2 (the patent) unpatentable ’735 un- der 35 U.S.C. 103. We affirm.
I. BACKGROUND A. The Invention The invention is directed to a method of treating disorders; human mental method treating depression involves in hu- (3—di- mans the oral administration of 5— methylaminopropylidene)dibenzo[a, d][l, 4] cycloheptadiene (commonly known as and Co., Inc., Charles M. Caruso Merck & hereafter referred to as “amitriptyline”), or Rahway, N.J., argued appellant. for With hydrochloride hydrobromide salts him on brief Lippert, was Neis T. of Fitz- thereof, particular dosage in a range. Am- Celia, patrick, Harper Scinto, & New York itriptyline following has the chemical struc- City. Of counsel were Mario A. Monaco ture: Sudol, Jr., Co., Michael C. of Merck & Inc., Rahway, N.J. Schafer, Sol.,
Richard E. Associate Office Sol., Arlington, Va., argued appellee. for
With him on Joseph brief were F. Nakamu-
ra, Sol., McKelvey, and Fred E. Deputy Sol. Co., 776,464,
1. Ex (PTO Parte Merck Appeal Reexamination No. Bd.Pat.App., No. 480-01 90/000264, (PTO Appeal 25, 1982), Bd.Pat.App. No. 607-66 p. Feb. JA 23. Int., 28, 1985), May p. opinion & JA 7. In its expressly adopted reasonings Board in its 3,428,735, 2. U.S. Patent No. issued to Edward L. (for patent) opinions, earlier reissue the 735 Ex Engelhardt February was based on Engelhardt, Parte Applica Edward L. Reissue 662,907 patent application Serial No. filed Au- 776,464, (PTO Appeal tion No. No. 424-40 Bd. gust continuation-in-part patent 1967 as a Pat.App., 1980), Apr. p. JA 13 and 855,981 Ex Parte application Serial No. filed Nov. Engelhardt, Application Edward L. Reissue No. invention, representative 1982), As claim 10 appeal was dismissed subject for lack of jurisdiction.6 reads: matter treating 1. A method of human men- application reissue protested involving depression which Laboratories, tal disorders (Biocraft), Biocraft Inc. inter- comprises orally administering hu- venor appeal. current Biocraft is 5-(3-dime- by depression plaintiff also the *3 litigation man affected a related pending in the dibenzo[a, U.S. District Court thylaminopropylidene) d][l, for the Jersey District of New which validity the 4]cycloheptadiene or its non-toxic salts infringement and patent of the ’735 is in daily dosage mg. of 25 to 250 of said issue. See Laboratories Inc. v. compound. Biocraft Co., Merck & Civil Action No. 77-0693 Remaining 2 and 3 dependent claims (D.N.J.). The district stayed court has fur- pertaining from claim and add limitations ther action in pending that case the final hydrochloride to the use of the hydro- outcome of pending the proceedings. PTO amitriptyline, respectively. bromide salts Proceeding C. Reexamination Proceedings Related B. Following dismissal of the appeal reissue application, March On an Serial. by CCPA, Co., the (Merck), Merck & Inc. (the 776,464 application), No. ’464 was filed assignee the patent, of the ’735 filed for patent.3 for reissue of the '735 All the granted request a for reexamina- application claims of the ’464 finally were patent. tion of the prosecu- As a result of rejected by the examiner under section 102 examiner, tion before the 1 through claims Code, of title United States and alterna- 3 of the application reexamination were tively under section of that title. Sub- finally rejected under 35 U.S.C. 102 as § 424-40) sequently, appeal (Appeal an No. anticipated by prior references; art was taken to the Board4 which affirmed claims rejected were also under 35 U.S.C. rejections. the examiner’s Additionally, being 103 as obvious over references cit- § rejection the Board entered a new under 35 by ed ground the Board in its new U.S.C. 103 over a combination of refer- § rejection during entered the initial reissue previously by ences not cited the examiner. appeal. Finding patent the ’735 to be enti- 1.196(b) In accordance with 37 C.F.R. § tled to the benefit of the November (1985)5, appellant elected reconsideration filing parent date of application, its application by of the ’464 the examiner. 855,981, Serial No. the Board reversed the The rejection examiner maintained the en- rejection section 102 because the effective Board; by Appeal 480-01, tered No. filing application date of the antedated all the Board affirmed the examiner. The Board, the references cited therein. appealed Board’s decision was to the Court however, rejection sustained the for obvi- Appeals (CCPA). of Customs and Patent ousness under Expressly section 103. Upon the motion the Commissioner of adopting reasonings of its earlier reis- Patents and Trademarks and on the opinions, author- sue position the Board took the Dien, ity of art, view of the in combina- application (1) submitting 3. The reissue appropriate was filed as a “no after amendments facts, type existing showing defect” reissue under the then have the matter reconsid- examiner; 1.175(a)(4) (1980). provision C.F.R. ered That has (2) repealed. now waive reconsideration before the been examin- er and have the case reconsidered Board; or time, Appeals 4. At that the Board of Patent (3) decision, including treat the new Interferences was called the Board of Patent ground rejection, aas final decision in the Appeals. case. 1.196(b) provides 5. 37 C.F.R. § that when the Application 6. See In the Matter Edward Appeals ground Board of determines a new (CAFC Engelhardt, Appeal L. No. 82-611 Oct. rejection, appellant may 1982) (order dismiss). granting motion to tion, thorough knowledge publication of the in- The Kuhn disclosed the com- vestigative techniques in the medic- pound, imipramine, taught used art, the skilled inal chemical artisan compound very antidepres- was a effective expected tricyclic com- known Imipramine sant in humans. has the chem- pound, amitriptyline, to be useful as an ical structure antidepressant. D. The References upon by references relied the Board
were:
(1) Rey-Bellet (Rey-Bellet) et al. U.S. Pat- 3,384,663, (applica- May ent No. and differs from the amitripty- structure of 27, 1959); tion filed Mar. line replacement of the unsat- *4 (2) Kuhn, Schweizerisehe Medizinische urated ring carbon atom the center with 35-36, pp. No. Wochenschrift, Vol. nitrogen taught atom. Kuhn a recom- 1957); (Aug. 1135-1140 dosage mg per mended of day pos- 75-150 — (Lehman), (3) Lehman et al. Canadian sibly mg if 200-250 the smaller doses Journal, Psychiatric Association “The proved ineffective. Depressive of Treatment Conditions with publication The Lehman disclosed the re- (G 22355)”, Imipramine pp. vol. No. study sults of a Canadian of the effects of (Oct. 1958); 155-164 imipramine symptoms depression on the of (4) Friedman, Symposium First On confirmed, This humans. article for the Correlation, “In- Biological Chemical part, teachings most of the Kuhn arti- Replacements Upon fluence of Isosteric cle. Biological Activity”, pp. (May 296-358 object publication The of the 1950); Friedman survey isosterism, history was “to of to (5) Burger, Journal Chemical Edu- of classify replace- the varieties of isosteric cation, Approaches Drug “Rational literature, ments which are recorded Structure”, 8, pp. Vol. No. 362-372 replace- and to note the influence of these 1956); (Aug. biological activity ments on the of com- (6) (Petersen), Petersen et al. Arzneimit- pounds.” Friedman defined isosteres as tel-Forschung, pp. Vol. No. 395-397 atoms, pe- ions or molecules in which the (1958); ripheral layers of electrons can be con- (7) 43,162, Report Roche Research No. Compounds identical. sidered which fit (Nov. 1957); pp. 1-9 definition broad and exhibit the same (8) 43,169, Report Roche Research No. biological activity were termed “bioisoster- pp. 1958); (Apr. 1-8 Further, respect ic.” with to the medicinal (9) 52,195, Report Roche Research No. theory chemists’ use of the of “isosteric pp. (Sept. 1958) (collectively 1-13 called replacement” replace- or “bio-isosteric Reports”). the “Roche predict properties ment” as a tool of Rey-Bellet patent amitrip- The disclosed compounds, Friedman commented that: tyline hydrochloride Proper- and its salt. synthetic organic chemist in- [t]o amitriptyline taught by ties of the refer- chemistry, every terested medicinal activity upon ence included a “manifold physiologically compound active phar- central nervous system,” as well as challenge known structure is a chal- —a macological properties, and medicinal such it, lenge perhaps either to better or mere- “narcosis-potentiating, adrenolytic, as seda- it____ ly equal tive, antihistaminic, antiemetic, antipyretic attacking hypothermic.” Rey-Bellet ways did dis- There are numerous problem____ close or otherwise teach that such a One the methods possessed antidepressive properties. frequently, very which has been used success, is that interchange often with of isosteric and unsat- examples replacement. type of this urated carbon atoms. replacement very in the literature are Burger publication also discussed numerous, and the fruitful results theory of “bioisosterism” and its use- sulfonamides, antimetabolites, fields in designing drugs fulness upon new based and antihistamines well known. knowledge compounds. “lead” page Finally, Friedman at Friedman publication taught, inter The Petersen groups various disclosed atoms or of atoms alia, properties (a ehlorpromazine bioisosteric, including interchange phenothiazine derivative) chlorprothix- and the oxygen unsaturated carbon atom (a 9-amino-alkylene-thioxanthene ene de- biological
which often resulted in similar rivative), Friedman, compounds having these activity. however, did not dis- the fol- lowing close otherwise teach as bioisosteric the structural formulas: *5 that, Petersen concluded when the Reports The Roche revealed the results ring atom located in the central comparing pharmacological from tests phenothiazine compound interchanged properties amitriptyline imipramine. with an unsaturated carbon atom as in the reports indicated that the two com- corresponding 9-amino-alkylene-thioxan- pounds very variety were similar in a compound, pharmacological prop- thene properties, including their action as tran- erties of the thioxanthene derivatives re- quilizers having narcosis-potentiating ef- very strongly properties semble of the similarity fects. Because of this and be- corresponding phenothiazines. Using the amitriptyline imipramine cause were theory of replacement, isosteric Petersen related, structurally Roche scientists con- predicted similarity properties: this in amitriptyline cluded that should be clinical- Structural per- chemical considerations ly depression tested for alleviation—a expectation mitted the that the 9-amino- property imipramine. known In the alkylene-thioxanthenes ... would show pharmacological guideline for the clinical great similarity corresponding phe- to the (which testings amitriptyline was la- They nothiazines. should be more sim- 4-1575), ilar in their phe- Preparation behavior to that of the belled Roche Ro nothiazines than the saturated 9-amino- Reports Roche stated that alkyl-thioxanthenes. physical From the is to be noted that a “tofranil-like [i]t $ point of view the -electron distributions already expected by effect” is to be us $ (sites -electrons) are almost the same ing a dose 1U-lk that of Tofranil. Side phenothiazine derivatives and in appear effects which can are ... sedative the 9-aminoalkylene-thioxanthenes with effects, atropine-like appear such as stabilizing conjugated their link- double Tofranil.[7] also with age ring between C9 the thioxanthene and the first appeal C-atom of the side chain. must We decide whether appellant’s pri- invention would have been page compounds Petersen at 3. The were prior ma facie obvious over the available having strong depres- disclosed as central i.e., sive, record; and, obvious, tranquillizing, action in if animals. art so whether imipramine. 7. Tofranil is a tradename used for
1096
prima
ring
facie case has been rebutted
in the central
of amitriptyline. To
obviousness,
unexpected
evidence of
results.
show
it was necessary to de-
knowledge
termine from
already available
appellant’s
the art at the time of
inven-
II. DISCUSSION
tion that one skilled in the medicinal chemi-
opinion
problem,
In its
on this
the Board
expected
cal art
amitriptyline,
would have
expressly
guidelines
followed
of Gra
imipramine,
like
to be useful in the treat-
Co.,
1, 17-18,
ham
Deere
383
v. John
U.S.
depression
ment of
in humans.
In re Pa-
684, 693-694,
545,
86
15
S.Ct.
L.Ed.2d
148
381,
pesch,
USPQ
315 F.2d
137
43
USPQ
(1966),
466-67
and made find
1963).
ings
inquiries
specifically
factual
set
forth
that decision. These factual find
Board,
As found
the Roche Re-
ings
accepted
they
must be
unless
ports recognized the
relationship
structural
clearly
Wilder,
erroneous.
736 F.2d
amitriptyline
imipramine
between
1516, 1520,
(Fed.Cir.1984),
USPQ
concluded
amitriptyline
should be test-
denied,
1209, 105
rt.
469 U.S.
S.Ct.
antidepressant
fact,
ed for
ce
its
activities. In
(1985);
1097 1390, 1387, USPQ 114, taught as F.2d 174 116 Petersen bioisosteric found that nitrogen and unsat- interchange 1972). of the Clearly, amitriptyline imipra- precise structur- atoms—the urated carbon mine, psychotropic drugs, both known imipiamine and ami- al difference between closely structurally expecta- related. The triptyline.9 tion that the similar structures would be- suggested no clear error the Board’s similarly We see have was in the Roche teachings as to the determination Reports. In combination with those teach- references, In prior art combination. ings, prior teaching precise art that the teachings, show a close view of these which amitriptyline structural difference between similarity (psy- and a similar use structural imipramine involves a known bioisos- chotropic drugs) between replacement provides teric sufficient basis ordinary skill in the imipramine, one of required expectation success, for the arts, possessed of the chemical medicinal hindsight.10 without resort to Obviousness investigative techniques knowledge of the require not predictability. does absolute drug design phar- field of used Lamberti, 747, 750, In re 545 F.2d 192 macological predictability, would have ex- 278, (CCPA 1976). USPQ Only a rea- imipra- amitriptyline to resemble pected expectation sonable that the beneficial re- depression in hu- mine in the alleviation necessary sult will be achieved is to show agree with the Accordingly, we mans. 887, Longi, obviousness. In re 759 F.2d prima appellant’s invention was Board USPQ (Fed.Cir.1985). prior over the art of record. facie obvious traversing In the Board’s decision appellant’s We also find untenable obviousness, urged appellant has arguments away that Petersen teaches premised on an the Board’s decision appellant’s from invention. Non-obvious impermissible try” standard. “obvious attacking ness cannot be established that there was no moti Appellant contends individually rejection where the references prior appel art to arrive at vation teachings upon is based of a combina try is not lant’s invention. “[O]bvious Keller, of references. 642 F.2d tion U.S.C. 103.” In re the standard (CCPA 1981). USPQ Antonie, in, read, Thus, Petersen must be iso omitted). Rather, (CCPA 1977) (emphasis lation, fairly it teaches in but for what references, the test is whether the taken with the art as a whole. combination whole, suggested appellant’s teaching interchange of the That is that the ordinary to one of skill invention atoms nitrogen and the unsaturated carbon medicinal chemical arts at the time the Simon, compounds so modified are re 461 is isosteric and invention was made. In *7 ist, concept predicting concept recognize of p. of that as a means JA 372. His view was that the pre- isosterically-related biological properties could not be used in 1959 to bioisosterism in amitriptyline antidepressant in dict the effects compounds prior to 1959. pharmacological differences between imi- or the Craig pramine amitriptyline. suggest Dr. stated: so far as to that 9. Petersen even went relationship apparent between the bioisosteric my opinion in afforded "isosterism” [I]n specific pharma- interchange predicting of and unsaturated for the the the no basis humans, my utility chloroprothix- belief design and it is ceutical led to the of carbon atoms today____ I do is still true compound that that expectation in the that the ene activity carryover tranquilizing the of believe biological activity chlorpro- as share the same chlorprothixene chlorpromazine to af- from Petersen, p. supra, at 395. mazine. See predicting basis for forded a reasonable properties carryover antidepressant from of Reports teachings as well 10. The of the Roche imipramine amitriptyline. to distinguish this case as the Petersen reference JA, Craig, pp. Affidavit of Paul N. 374-75. 729, 731, Grabiak, USPQ 769 F.2d from clearly Plainly erroneous the Board was not 1985) ("there (Fed.Cir. is no motive testimony. discounting that There was inde- in pendent required the modification the cited art to make contrary. evidence in the record appellants’ compounds”). to arrive at Friedman, Burger references and Petersen expected possess biological prop- Further, to similar imipramine. effect than Dr. erties. depressed patients Schildkraut notes that responded differently amitriptyline persuaded appel Neither are we imipramine, responding some to one lant’s contention that the Board erred in and not the other or more favorably to one contemporaneous relying indepen on the than part, to the other. For the most support of its hold dent invention others symposium record of the cited confirms the ing of As we have said obviousness.11 differences noted the Schildkraut affida- earlier, teachings prior of the art refer vit.14 That practicing record also counseled adequately support ences combination physicians choosing spectrum from the However, the Board’s conclusion. the addi tricyclic (a antidepressants term which tional, although unnecessary, evidence of amitriptyline imipramine) includes contemporaneous probative invention is particular drug pa- useful for an knowledge in individual “the level of the art at the tient. time the invention was made.” In re Far 714, 720, renkopf, After a careful consideration of all the
(Fed.Cir.1983). evidence, persuaded we are Board Unexpected prima Results: A fa in determining alleged did not err that the cie case of obviousness can be rebutted unexpected properties amitriptyline unexpected evidence of results. In re Dav unexpectedly not so different from the ies, USPQ 381, F.2d 384 properties imipramine, prior the closest 1973). In rebuttal of the PTO’s art, prima as to overcome the facie show- prima appellant facie case has asserted ing of obviousness. The art of record that, compared imipramine, amitripty clearly taught that amitriptyline was a unexpectedly potent line has a more seda known sedative.15 The evidence before us stronger anticholingeric tive and a effect. (which was, course, Board) before the contention, In support appellant of this has tricyclic further revealed that all antide- relied on Joseph an affidavit of Dr. J. pressant drugs, general, possess the sec- Schildkraut,12 psychiatrist and a Profes ondary properties of sedative and anticholi- Harvard, Psychiatry sor of at and also on a nergic Specifically, effects. the record published symposium physi record of a during prosecution showed that psychiatrists cians and concerned with the application, appellant reissue submitted an depressed patient.13 treatment of “Using article tricyclic entitled antide- pressants” which recognizes compar- Dr. Schildkraut’s affidavit included a table ing pharmacological properties tricyclic some differences between known antide- amitriptyline imipramine including pressant drugs.16 proper- Included these potent fact that is a more ties were anticholinergic sedative and ef- stronger anticholinergic sedative and has a antidepressants.17 fects of the known Engelkardt, Appeal Rey-Bellet, Ex supra, Parte Edward L. No. 15. col. line 16. 424-40, 23-24, 22(1)— supra pp. pp. JA note 22(m), where the Board indicated that evidence Care, "Using Tricyclic Antidepres- 16. Patient groups before it revealed four other sants,” 28-33, 35-36, 39-40, 43-45, 49-52, pp. independently contemporaneous inventors 57-58, 63-64, 67-68, 71, 73-76, 78, 81, 84-85, ly antidepressant amitriptyline’s discovered 15, 1979); (May Appen- see also Commission’s *8 properties using reasoning thorough based on a dix, pp. CA 17-45. knowledge investigative techniques, which in isosterism, concept cluded the used in the Symposium, Depression Today— 17. See also the medicinal art area. Questions, 13, Experts supra Answer Your note 315, Schildkraut, p. Joseph p. 12. at where Dr. Hollister Affidavit of J. JA 366. indicates that choosing spectrum tricyclic when from the Symposium, Depression Today Experts 13. An- — drugs, antidepressant the choice is based on Questions, p. swer Your JA 309. (1) pharmacological including three actions the (2) amount of sedation the amount of anticholi- sympo- 14. Dr. Schildkraut was a member of the (3) nergic drugs effect and the nature of the in sium.
1099 BALDWIN, Judge, alleged dissenting. difference Circuit Thus, appears that the it amitriptyline and imi- between properties by rejection The the board is flawed be- degree rather than a matter of pramine is analyze it did not cause the invention ac- effects, Moreover, sedative as to the kind. cording requirement of 35 U.S.C. slight only a difference the article revealed 103. The board wrote: § compounds. Amitripty- the two between considering issue before us “highly sedative” line was characterized patent- instant claims on their for merits imipramine was “somewhat less while ability having the artisan whether 18 amitriptyline.” Regard- than [sedative] requisite pertinent in the skill art area effect, anticholinergic the article ing the knowledge prior and a available drugs anticholinerg- both have showed that employ art would have been motivated to degree. These but to a different ic effects amitriptyline in the treatment of human unexpected truly results. are depression. opinions in one of its reissue Board found is, That whether it have would been obvi- (incorporated in the reexamination decision try amitriptyline antidepres- ous as an regard to the seda- appeal): now “[i]n by ap- sant. Guided the disclosure of the anticholinergic properties of ami- tive and pieced together plicant, the board informa- are not convinced that triptyliné, we patents, journal articles, tion from various [amitriptyline] material side effects of this papers, and concluded: significantly unexpectedly different position having It remains our that one properties of those exerted from the level ordinary skill this art would are[sic] imi- antidepressant, art by the closest concept have been familiar with the 19 pramine.” bioisosterism and because of this knowl- that, it is while there are The core of edge would have concluded that degree differences between some i.e., compound, amitriptyline, known amitriptyline imipramine, properties of potentially would be useful as an antide- compounds expectedly have the same [Emphasis pressant. ours.] activity. In type biological the absence is, try That it would have been obvious to properties of evidence to show that amitriptyline antidepressant. as an Obvi- compounds appreci- differed in such an ous-to-try patentability is not the test for really degree that the difference was able U.S.Q. under 35 103. This court and its unexpected, we do not think that the Board CCPA, repeatedly re- predecessor, the appellant’s erred in its determination that Goodwin, approach. In re 576 jected that pri- insufficient to rebut the evidence was 1, (CCPA 1978); 375, 377, USPQ F.2d 198 3 The fact that ma facie case. Antonie, 618, 620, In re 559 F.2d 195 respectively, helped some imipramine, 6, (CCPA 1977); Lindell, USPQ re 385 8 In patients appear does not and not others 521, USPQ F.2d 523 Board, by the a dif- significant. As noted 928, 1967); Tomlinson, 363 F.2d structure, although slight, ference (CCPA 1966); USPQ Papesch, re In produce some differ- expected have been 1963); USPQ (CCPA F.2d in activity. ence Grabiak, re see also In sum, In the claimed inven- we hold that (Fed.Cir.1985). one tion would have been obvious Congress rejected approach has also Accordingly, the ordinary skill in the art. enacting the second sentence of 35 decision of the Board is “[patentability which states U.S.C. § negatived not be the manner shall AFFIRMED. Engelhardt, Appeal No. primarily blocking uptake Ex Parte Edward L. of serotin or no- 19. 480-01, p. repinephrine. supra p. note at JA 34. Care, “Using Tricyclic Antidepres-
18. Patient sants,” p. supra note *9 pounds made.” revis- which the invention was The with similar chemical structures “it is im- er’s note this sentence states on sometimes a behave similar fashion in a long it from toil material whether resulted biological system. compound Once a such a of experimentation and or from flash been has tested and found to have the genius.” biological activity, same it is called “bio- isosteric.” analysis attack obvious-to-try The is an making on the of an invention that method Friedman also teaches an that isosteric penalizes of en- specifically people areas compound “may have activity the same as only by are won deavor where advances or more original, usually may it have great pharmaceu- The expense. effort and antagonistic (Emphasis an effect.” add- particularly tical field is hard hit because ed.) explains Friedman that order to of there is structures an overabundance predict biological activity accuracy, with Consider, try. that for ex- are obvious to ideally (1) one should know the mechanism ample, the Petersen reference which by original drug (2) which the acts and majority possibili- to cites demonstrate part original what structure of the ty may replaced by be that a atom drug original drug is critical to activi- journal a atom. double-bonded carbon This ty.2 That reference unequivocally also attempt drugs article records an to find comparisons states should be made in of endogenous useful for treatment living systems, but such information is not i.e., psychoses, tranquilizers. The re- easily available. That reference relies on eighteen searchers tested chemicals with in vitro testing, specifically and it states closely related structures. These materials that in vitro results may may or not corre- mice, and injected compared were into for with clearly late clinical studies. It also ability asleep. their to mice make the fall that, purposes states for its discus- may The results these tests tanta- be sion, biological as absorp- activities such useful, lizing guide a and but as for tion, distribution, (detoxifica- conjugation that, agree further research. I based tion), taste, drugs side odor effects this information and the other references ignored. will be Friedman concludes that board, cited by the the researcher with compounds with similar structures need ordinary in the skill art would be motivated bio-isosteric. be investigate possibility substituting to Burger The nitrogen. a reference does discuss bio- double-bonded carbon for atom designing The and its researcher would be to isosterism usefulness also motivated drugs. every test other structural variation in Pet- new Its evaluation of bio-isosterism ersen, predicting drug as well as a host others. Under tool for activity as a is as an obvious-to-try analysis, any of these follows: ultimately structures is to which shown be However, gradual if can one achieve a antidepressant effective an human change biological behavior follow
beings unpatentable be because accurately step it at each of minor struc- logical plan. researcher dared to follow a alteration, one is tural bound enhance another, suppress property, one and ulti- majority board also err mately drug a arrive at suitable for ther- reading certainty much teach- too into the ings apy. disconcertingly to this They of the references. con- Shortcuts have not process found, sidered a the references as whole. Fried- tedious not been is phenomenon probably responsible man discusses the com- this for the still simply beings. theory 1. therefore The term “bio-isosteric" is human of bio-isosterism as testing. is conclusion drawn after The label majority nothing used the board and more properly system purpose for limited analysis less than an of structural obvious- compounds which ple, tested. were For exam- ness. drugs two could be bio-isosteric with re- spect making asleep, mice bio- fall and not any Neither reference nor the others particular dosage isosteric when tested at a level purport piece either disclose of information. high pressure for the treatment of blood *10 drugs opinion new useful prevailing or easily by more discovered most
will be ROLLS-ROYCE LIMITED and procedures, Renishaw, empirical pic, Appellees, less page at v. structural Slight stereochemical GTE VALERON may considerably alter the bio-
changes CORPORATION, Appellant. compound. of a Patient vari- logical role Appeal No. 86-761.* least a number of of at reasonable ation is to this structures still the answer Appeals, States United Court of question, Federal Circuit. 370. page Sept. reports background in- Roche contain pharmacological about various
formation amitriptyline. information
effects toxicity testing from for its derived This tranquilizing animals. effect on would be essential to a decision
information clinically It is not suffi- drug. test
to drug useful for
cient to show would be gave
treating beings. Congress human difficulty of recognition
pragmatic
determining drug is useful whether a new amendment
by its enactment the 1962 taken
21 U.S.C. 321. That action was problems by another
response to caused
tranquilizer, thalidomide. references, nor the other
Neither these ma- cited and the
references the board purport the worker with
jority teach amitriptyline is
ordinary skill in the art that treating depres- drug that is useful for beings. That conclusion
sion human
steps information removed from the re- I would
presented by these sources.
verse.
* January consoli- with No. 86-761. court ordered On Rolls-Royce’s cross-appeal, No. 86- dation of