Killing One Bird with Two Stones: Pharmaceutical Patents in the Wake of Pfizer v Apotex and KSR v Teleflex

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1 Killing One Bird with Two Stones: Pharmaceutical Patents in the Wake of Pfizer v Apotex and KSR v Teleflex Janis K. Fraser, Ph.D., J.D. June 5, 2007

2 The pre-apocalypse obviousness world Pfizer v. Apotex KSR v. Teleflex Pharmaceutical patents newly at risk Obviousness criteria, post-pfizer/ksr Keys to overcoming obviousness challenges Consequences to pharma industry 2

3 The Pre-Apocalypse World Graham Factors - scope and content of the prior art - differences between the prior art and the claims - level of ordinary skill in the art 3

4 The Pre-Apocalypse World Graham s secondary ( objective ) indicia of nonobviousness - unexpected results - commercial success - long-felt but unsolved needs - prior effort and failures - willingness of others to license - copying by others - skepticism of experts - tribute by experts 4

5 The Pre-Apocalypse World Federal Circuit s 25-year-old obviousness test - All limitations are found in the art - Teaching, suggestion or motivation to combine ( TSM test ) is found in the art or in the nature of the problem to be solved - Expectation of success is found in the art - Obvious to try is not the standard - Teaching away - Objective indicia 5

6 Pfizer v. Apotex, 480 F.3d 1348, 82 U.S.P.Q.2d 1321 (Fed. Cir. 2007) 6

7 Pfizer v. Apotex: Facts amlodipine and salts thereof: US 4,572,909 (1982 priority date) maleate salt - selected problems (instability and stickiness) noted April clinical trials with capsule form 7

8 Pfizer v. Apotex: Facts 7 alternatives identified and tested in 1984 Besylate salt - Selected October In clinical trials by Filed priority application in 1986: US 4,879,303 - Launched as product (Norvasc ) in

9 Pfizer v. Apotex: District Court 303 claims not obvious No motivation in the art discloses amlodipine salts, but not amlodipine besylate - Berge lists many salts and says besylate is rarely used (0.25%) No expectation of success: no reliable way of predicting the influence of a particular salt species on the behavior of a parent compound Surprising results: better properties than maleate Other objective consideration : Pfizer s switch to besylate salt 9

10 Pfizer v. Apotex: Federal Circuit Reversed District Court Claims are obvious over 909, Berge, and references disclosing besylate salts of other compounds 10

11 Pfizer v. Apotex: Federal Circuit Motivation to combine - Does not have to be found explicitly in prior art references sought to be combined - Can be in any number of sources ¾ common knowledge ¾ prior art as a whole ¾ nature of the problem itself 11

12 Pfizer v. Apotex: Federal Circuit Motivation to combine - Can be gleaned from the nature of the problems encountered with the amlodipine maleate tablet formulations sought to be solved by the inventors! Based on undisclosed problems discovered by inventors?? 12

13 Pfizer v. Apotex: Federal Circuit Motivation to combine - Fact that Berge says besylate is rarely used (0.25%) doesn t matter ¾ Irrefutable evidence shows that a skilled chemist at the time would simply make known pharmaceutically-acceptable salts of whatever active ingredient with which he or she was working at the time ¾ Number of acceptable anions was not unlimited 13

14 Pfizer v. Apotex: Federal Circuit Motivation to combine - Fact that the art showed only unrelated compounds prepared as besylate salts doesn t matter ¾ Art described besylate salt as useful in promoting stability, solubility, etc. 14

15 Pfizer v. Apotex: Federal Circuit Reasonable expectation of success - Fact that there was no reliable way to predict the influence of a particular salt species doesn t matter ¾ Need only a reasonable probability of success ¾ Inventor expected that each of the 7 on his list would form a salt with improved characteristics compared to maleate! Inventor s own expectations used as evidence of what constitutes reasonable expectation of success 15

16 Pfizer v. Apotex: Federal Circuit Obvious to try (not obvious if motivation is merely to vary all parameters, where the prior art gave no direction) Here not numerous parameters only one Here the art (inventor?!!) expected besylate salt would form Other art clearly directed the artisan to choose besylate salts 16

17 Pfizer v. Apotex: Federal Circuit Obvious to try Required only routine experimentation to confirm the properties ¾ Distinguished routine experimentation used to discover a new compound ¾ Analogized to optimization of a range ¾ Dismissed significance of salt s effect on properties of the drug because did not affect therapeutic effectiveness 17

18 Pfizer v. Apotex: Federal Circuit Secondary considerations Pfizer s switch to besylate ¾ No evidence to support Dist. Court s conclusion ¾ Pharmaceutical companies are in the business of R&D 18

19 Pfizer v. Apotex: Federal Circuit Secondary considerations Unexpectedly superior results (on stability and stickiness) ¾ No evidence that the properties were unexpected ¾ Pfizer says properties are not predictable, so can t say art expected lesser results ¾ Inventor expected an improvement! So inventor s own expectations used against him ¾ Art (inventor??) would have expected all 7 salts to work and that one would show up as the best after routine optimization ¾ Even if unexpectedly superior results, doesn t overcome the strong case of obviousness 19

20 Pfizer Foreshadows KSR Flexible TSM test Motivation can be derived from problem to be solved Obvious to try can mean obvious 20

21 KSR v. Teleflex, 550 U.S. (2007) 21

22 KSR v. Teleflex: Facts Teleflex patent claimed adjustable automobile pedal with electronic sensor to control throttle prior art - adjustable pedal with mechanical throttle control - non-adjustable pedal with electronic sensor to control throttle 22

23 KSR v. Teleflex: District Court summary judgment of obviousness - Graham Factors ¾ found little difference between art and claim - TSM test ¾ hypothetical motivation different from patentee s - commercial success of invention insufficient to override obviousness conclusion 23

24 KSR v. Teleflex: Federal Circuit non-precedential opinion reversed summary judgment of obviousness and remanded for trial 24

25 KSR v. Teleflex: Federal Circuit said District Court did not apply TSM test strictly enough - lacked findings as to the specific motivation - nature of the problem was insufficient basis here because the problems addressed by prior art were different from that addressed by Teleflex obvious to try does not constitute obviousness 25

26 KSR v. Teleflex: Supreme Court Unanimous decision 26

27 KSR v. Teleflex: Supreme Court Reaffirmed Graham s expansive and flexible approach 27

28 KSR v. Teleflex: Supreme Court Rejected rigid approach of Federal Circuit s TSM test - Reason to combine need not be in the prior art can be in common sense of a POSITA of ordinary creativity - Problem to be solved need not be the patentee s problem - Obviousness can be based on obvious to try, if there is a design need or market pressure to solve a problem, combined with a limited number of predictable solutions 28

29 KSR v. Teleflex: Supreme Court Reaffirmed that teaching away is evidence of nonobviousness (citing United States v. Adams, 383 U.S. 39 (1966)) 29

30 KSR v. Teleflex: Supreme Court Reaffirmed that unexpected results are evidence of nonobviousness (citing Adams) 30

31 KSR v. Teleflex: Supreme Court Reaffirmed that conclusory statements re motivation are insufficient must be some articulated reasoning with some rational underpinning important to identify a reason that would have prompted one of ordinary skill in the relevant field to combine the elements 31

32 KSR v. Teleflex: Supreme Court Theme #1: common sense Common sense teaches, however, that familiar items may have obvious uses beyond their primary purposes, and in many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle. If [pursuing a finite number of known options] leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. 32

33 KSR v. Teleflex: Supreme Court Theme #1: common sense Rigid preventative rules that deny factfinders recourse to common sense, however, are neither necessary under our case law nor consistent with it. Our suggestion test is in actuality quite flexible and not only permits, but requires, consideration of common knowledge and common sense. 33

34 KSR v. Teleflex: Supreme Court Theme #2: predictable The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. [When] a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result. 34

35 KSR v. Teleflex: Supreme Court Theme #2: predictable If a person of ordinary skill can implement a predictable variation, Section 103 likely bars its patentability. A court must ask whether the improvement is more than the predictable use of prior art elements according to their established functions. 35

36 Pharmaceutical patents newly at risk Follow-on patents Salts ¾ Pfizer v. Apotex Enantiomers Controlled release ¾ Alza v. Mylan, 464 F.3d 1286 (Fed.Cir. 2006) Formulations Delivery route or regimen Combinations of old drugs New indications for old drugs 36

37 Pharmaceutical patents newly at risk Primary patents Second or subsequent drug in a class Minor modification of a known compound 37

38 Obviousness criteria, post-pfizer/ksr Were all elements present in the art? 38

39 Obviousness criteria, post-pfizer/ksr Was there a common-sense reason to combine? In the art In the nature of the problem addressed by patentee (even if that problem was known only to the patentee???) In the nature of any problem that existed in the art Has to be articulated (S.Ct. and USPTO) Teaching-away may neutralize at least some of such reasons 39

40 Obviousness criteria, post-pfizer/ksr Obvious-to-try can in some cases be adequate to supply the motivation to combine When varying a single parameter (not multiple), using routine experimentation and a finite number of known variations Less likely when used to discover a new compound as opposed to selecting a variant with improved characteristics Less likely when the improved characteristic is therapeutic effectiveness as opposed to physical properties such as stability or stickiness Variations must have been within the capabilities of POSITA ( but when aren t they?) 40

41 Obviousness criteria, post-pfizer/ksr Was there a lack of expected success in the art? Need only a reasonable probability of success Undermined by proof that inventor expected the invention to work (This (from Pfizer) seems wrong, so may not hold) Teaching away is best evidence 41

42 Obviousness criteria, post-pfizer/ksr Were the results surprisingly good? Need to prove what the art would have expected Undermined by arguing that the field was unpredictable Undermined by proof that inventor expected at least one of tested variations to be better than the prior art (Again, seems wrong to use inventor s expectations as proof of what the art expected) 42

43 Obviousness criteria, post-pfizer/ksr Other objective indicia of nonobviousness Won t help if the court is convinced the prima facie obviousness case is strong 43

44 Keys to overcoming obviousness challenges Find a teaching away in the art Establish surprising results (In litigation) show that the inventor did not predict the invention would work until it did work 44

45 Keys to overcoming obviousness challenges Argue that problems discovered and solved by inventor are part of the invention, not part of the prior art Argue that the asserted motivation lacks common sense 45

46 Keys to overcoming obviousness challenges Emphasize benefits in terms of therapeutic effectiveness rather than physical properties Characterize the invention in terms of discovery rather than mere optimization Emphasize non-routine nature of the experimentation needed to discover the invention 46

47 Consequences to pharma industry Pro-competitive effect: For existing drugs, it will be harder to block generic entry into market after primary patent expires Earlier generic entry However, shorter period of exclusivity may change the calculation of whether to move forward with developing the NCE in the first place, so may turn out to be anticompetitive 47

48 Consequences to pharma industry Anticompetitive effect: Some promising NCE s or new formulations or new indications will not be developed because no patent protection at all No patent means development cost can t be recouped, so no one will be willing to develop the drug Fewer marketed drugs means less choice for consumers Even generics will suffer because fewer drugs to copy 48

49 Consequences to pharma industry Unlikely to be much counterbalancing benefit to pioneers Broad platform patents that block new drug development not as vulnerable to obviousness attack ¾ Research tools ¾ Broad genus of novel compounds with new activity 49

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51 Janis K. Fraser, Ph.D. Fish & Richardson P.C. 225 Franklin Street Boston MA Fone: Fax: