提起牴觸/衝突程序（Interference Proceeding）的功能是釐清誰是發明人，主要目的是奪回專利權，或是無效對手的專利，其中討論的主題著重在是專利性，此案例討論到的是顯而易見性（35 U.S.C. 103）。
牴觸程序可參考前篇報導：CRISPR的專利爭議討論 - 牴觸程序（http://enpan.blogspot.tw/2017/03/crispr.html）
對照專利：
主要方（簡稱"UC"）：
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, UNIVERSITY OF VIENNA, and EMMANUELLE CHARPENTIER (Application 13/842,859)
次要方（簡稱"BROAD"）：
THE BROAD INSTITUTE, INC., MASSACHUSETTS INSTITUTE OF TECHNOLOGY, and PRESIDENT AND FELLOWS OF HARVARD COLLEGE,
(Patents 8,697,359; 8,771,945; 8,795,965; 8,865,406; 8,871,445; 8,889,356; 8,895,308; 8,906,616; 8,932,814; 8,945,839; 8,993,233; 8,999,641 and Application 14/704,551)
專利性討論：
App. No. 13/842,859（簡稱'859案）：
'859案公開號為US2014/0068797，主張4件臨時申請案優先權，最早為2012年5月25日申請的No. 61/652,086，最晚的為2013年2月15日申請的No. 61/765,576，'859案公開專利範圍達155項，之後修正成為Claims 165-247，是最早佈局的專利母案，因此不急於「領證公告」。
'859案早於2015年9月接獲的OA中除了112與DP問題外，已具備可核准專利範圍，不過申請人UC顯然不滿足，在此之後除了答辯外，更提出本次討論的牴觸程序。
UC專利申請案App. No. 13/842,859（簡稱'859案）修正後可核准代表Claim 165：
US8,697,359（簡稱'359案）：
（請求最快的fast track快速審查，使得占了先機，可參考過去報導：生物技術的專利爭議與申請策略 - 有關CRISPR）
已經獲准一串專利的BROAD專利'359案反而是「較晚」申請的專利案，主張的優先權最早溯及2012年12月12日的臨時申請案No. 61/736,527，最晚為2013年7月2日的No. 61/842,322，時間範圍與'859案重疊（牴觸/衝突的來源之一），但整體較晚申請，但是提早搶得先機，獲准了不少專利，不過在牴觸程序或將來的訴訟中都會處於「答辯/被打」的角色。
BROAD代表專利：US8,697,359（簡稱'359案）公告的Claim 1：
1. A method of altering expression of at least one gene product comprising introducing into a eukaryotic cell containing and expressing a DNA molecule having a target sequence and encoding the gene product an engineered, non-naturally occurring Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)—CRISPR associated (Cas) (CRISPR-Cas) system comprising one or more vectors comprising:
a) a first regulatory element operable in a eukaryotic cell operably linked to at least one nucleotide sequence encoding a CRISPR-Cas system guide RNA that hybridizes with the target sequence, and
b) a second regulatory element operable in a eukaryotic cell operably linked to a nucleotide sequence encoding a Type-II Cas9 protein,
wherein components (a) and (b) are located on same or different vectors of the system, whereby the guide RNA targets the target sequence and the Cas9 protein cleaves the DNA molecule, whereby expression of the at least one gene product is altered; and, wherein the Cas9 protein and the guide RNA do not naturally occur together.
103議題：
兩者專利權是否牴觸，就看後案'359的專利範圍是否被前案'859所教示，或說是否相關領域一般技術人員可以由前案'859的技術內容輕易達成（或成功的合理期待）後案'359的請求項發明。
根據技術事實，後案'359發明係為應用在真核環境（eukaryotic environment）的CRISPR-Cas9系統，但前案'859並未限定在任何環境，就是界定出包括Cas9蛋白、單分子DNA標靶核糖核酸（RNA）的CRISPR-Cas9系統，並未限定任何範圍。
就「顯而易知性」的爭論而言，應用限定在某個範圍就為顯而易知性（或非顯而易知答辯），需要有合理的證據。
“The consistent criterion for determination of obviousness is whether the prior art would have suggested to one of ordinary skill in the art that this process should be carried out and would have a reasonable likelihood of success, viewed in the light of the prior art.”
“Obviousness does not require absolute predictability of success . . . [A]ll that is required is a reasonable expectation of success.”
所述成功的合理期待（reasonable expectation of success）需要許多證據，在這個領域特別需要「專家意見」，BROAD甚至引用了UC案發明人曾經公開表示出「CRISPR/Cas9」是個巨大的成功，但是卻無法確定是否可用在植物與動物細胞的真核環境，這句話可以表明用在真核環境的難度，也就是缺乏「成功的合理期待」。
以上描述證明'359案發明是前案所缺乏的成功的合理期待，但是，也不是寫一段用在「真核環境」的專利就可以順利獲准，也需要證據證明這個技術的"成功率"，這時BROAD提出CRISPR-Cas9實現在真核環境實驗成功的證據。這裡涉及十分專門的技術辯論。
"The contemporaneous statements cited by both parties persuade us that one of ordinary skill in the art would not have reasonably expected success before experiments in eukaryotic cells were done."
（不錯的審查態度）在實驗完成以前，終極的成功並非表示成功的合理期待。
"We are not persuaded that the ultimate success is indicative of the expectation of success before the experiments were completed."
（不錯的審查態度）終極的成功"無關"於是否相關領域技術人員可以在發明完成時合理期待了這個成功。
“That the inventors were ultimately successful is irrelevant to whether one of ordinary skill in the art, at the time the invention was made, would have reasonably expected success.”
如果實現在真核環境的CRISPR-Cas9是有動機去嘗試的，根據KSR判例，這可能仍是顯而易見的技術，在此申請人/發明人需要證明「別人的失敗」，也有案例如Abbott Labs. v. Sandoz, Inc., 544 F.3d 1341, 1352 (Fed.Cir.2008)，雖然大家都有動機嘗試這個發明，但知道這個目標不代表就是成立為顯而易知（knowledge of the goal does not render its achievement obvious）。
"We agree with Broad’s argument that a large reward might motivate persons to try an experiment even if the likelihood of success is very low."
"The desire for that payoff could motivate pursuit of the method, but ‘knowledge of the goal does not render its achievement obvious,’..."
許多他人的失敗證明這個系統缺乏成功的合理期待，因此，反過來證明BROAD的成果是非顯而易知。
"we are persuaded that the failures demonstrated with other systems would have indicated the lack of a reasonable expectation of success."
KSR的挑戰：
"還好"（對後案申請人BROAD來說），這裡PTAB的意見採用BROAD的答辯意見，以及許多案例對於"reasonable expectation of success"的論點，對於是否成功的合理期待的顯而易見討論，應從接近的先前技術的特定性質來看，也就是逐案討論，如果先前技術的嘗試是失敗的，仍非顯而易見，並非一體適用。
"These cases instruct us that whether or not one of ordinary skill in the art would have had a reasonable expectation of success for the purposes of determining obviousness depends on the specific nature of what was known from the prior art about closely related subject matter."
"The availability of only generalized instructions and evidence of failures with similar subject matter have indicated the opposite."
這是PTAB認為前案並未影響後案'359專利權的結論：
"Specifically, the evidence shows that the invention 7 of such systems in eukaryotic cells would not have been obvious over the invention 8 of CRISPR-Cas9 systems in any environment, including in prokaryotic cells or in 9 vitro, because one of ordinary skill in the art would not have reasonably expected a 10 CRISPR-Cas9 system to be successful in a eukaryotic environment."
Interference 106,048 最終決定檔案：
https://app.box.com/s/ogzbf7n5mbqfd17cmp3kqhjh0serdwk0（備份）
my two cents:
在競爭激烈的先進技術來說，「臨時申請案（provisional application）」顯得十分重要，否則時間一遲，就會處於被打的狀態。
在競爭激烈的先進技術來說，甚至其中相關人（申請人、發明人）的公開言論都會拿來用！自己說都沒用，反而在此案例中，對手的言論成為重要關鍵。
大家都在努力的方向就是合理期待的目標，KSR判例告訴我們這是顯而易知的技術，但，如果證明了別人的失敗，以及自己的成功，就是非顯而易知。
牴觸程序/衝突程序是這類爭議的一個救贖程序。
Ron
沒有留言:
張貼留言