X-Message-Number: 5700
Date: 03 Feb 96 18:48:15 EST
From: Mike Darwin <>
Subject: Patents and Nondisclosure

Ralph Dratman raises a very important and difficult issue which I would 
like to address at some length.  Ralph writes:

>>*Much of BPI and 21CM work is contract work.  Almost all of the work is
>>proprietary.  Course attendees will be required to sign a nondisclosure
>>agreement which applies to *specific* drugs, techniques and devices of a
>>proprietary nature which are under development or in patent.

>I was just beginning to wonder about this. To what extent are proprietary,
>non-public cryopreservants and protocols superior to publicly announced
>ones?

>Are there actually some cryo patients who have received care that the rest
>of us can't be told about?

>This is a compelling issue to me, because I've been doing some thinking 
and
>research about cryopreservation recently. I have some interesting ideas,
>but lack of public disclosure of other people's work (NB: over an extended
>period of time) could hold back progress and general understanding.

>Comments?

Here is my take on this issue:

1) Let's start with the simple questions:  Yes, patients have received what 
is, in my opinion, far superior treatment which has not been disclosed for 
proprietary reasons. Patients have also received terrible care:  pumped 
full of air, subjected to massive osmotic stress, held at multimolar 
concentrations of membrane eroding cryoprotectant at very high subzero 
temperatures for days...

2) > I have some interesting ideas,but lack of public disclosure of other 
people's work >(NB: over an extendedperiod of time) could hold back 
progress and general >understanding. 

Your concerns are very valid.  This is a source of intense frustration to 
me.  If you obtain ALL of the back issues of CRYONICS magazine from Alcor 
((800)367-2228) before my departure from Alcor  you will finf that both 
Jerry Leaf and I were very forthcoming about disclosing the many changes to 
proctocol made, and the (IMHO) many advances we made in delivering improved 
patient care.

However, there was a penalty to pay for this.  Several of our ideas were 
appropriated by others and used to raise literally 10 to 15 million dollars 
of money; which resulted n handsome profits to those involved.  This leaves 
a VERY sour taste in one's mouth, to say the least. Sourer still when you 
are publically and privately derided for things like using hydroxyethyl 
starch as the colloid, only to see your competitors use it, profot from it 
enormously, etc.

Further, very bad care of patients has been delivered with the cryonics 
organization or service provider refusing to disclose details under the 
guise of "proprietary interest."  I know (within reasonable bounds) for the 
bad-care issues to be true in these cases of nondisclosure because I have 
had access to both (non-polarized) personnel involved in delivering this 
care, and have seen paper documentation in some cases and raw video footage 
in others.

Not being able to make full disclosures is corrosive.  It creates an 
insulated world of delusion where patents and scecrets take on lives of 
their own and become like religious doctrine.  In the absence of criticism, 
scientific scrutiny, and, in short, evaluation by others, you enter a dream 
world free of feedback necessary to keep you on track.  Further, you cut 
yourself off from the tremendous intellectual resources, often given 
freely, which come your way when you TELL people honestly, and in detail 
about what you are doing and why. AND what your problems are!

2) So, how do we handle this problem? More to the point, how do BPI and *I* 
handle it.  An intermediate position is to disclose objective results and 
ALL relevant nonproprietary techniques used in patient care and then let 
the reader judge for his or her self.  If you say: "We have drug 21CM-005  
for problem N, and this patient experienced X,Y & Z with elimination of 
problem N, and patients treated under nearly identical conditions had 
terrible courses by comparison...well its an improvement.  But it still 
sucks.  Because the devil is in the detail and a discussion of the 
biochemistry, rationale, and detailed monitoriong during the research phase 
(which ALSO sometimes cannot be disclosed because it gives too many clues 
away) is also in my experience critical.

An example:  In the early 1970's Safar, et al published a paper 
demonstrating good neurological recovery of dogs following 12 minutes of 
global cerbral ischemia followed simply by (heart-lung machine supported) 
hemodilution with Dextran-40 and hypertensive reperfusion lasting for 
several hours.  Subsequent papers (there were many) by Safar and others did 
NOT show this result; the dogs were profoundly neurologically injured.  
When I spoke with Safar over lunch recently I asked him about this early 
work.  He said simply: "Oh, well you see we subsequently discovered that 
the critical variable was termperature post insult, which we were not 
controlling for; we were allowing (by accident) the dog's tmperature to 
drift down to 34 C while on bypass; this turned out to be the most 
profoundly protective factor by far!"  Since they wanted to pursue this and 
not be "scooped" they spent the next few years doing studies using 
post-ischemic hypothermic holding periods with great success; and they 
PUBLISHED this work.

Is this immoral?  No.  But it points out the problem; they made a discovery 
which needed rigorous documentation to have credibility, but that required 
TIME.  So even in academia, this happens.

3) Our patent lawyers and those of our contract researchers are VERY 
conservative.  They ask us not to make specific disclosures until after the 
patent is *issued* which takes about 12 to 24 months if it is 
straightforward, uncontested, and you are luckly.  It also costy about 
$7-$10K per patent.  While you can indeed "do it yourself" with US patents, 
this is in reality often a lousy idea unless you are a very good 
self-taught person AND unless your market is mostly US.  Some ideas just 
aren;t going to justify the up-front cost and getting investors to plunk 
down this kind of money for patents in the cryonics "market" is a bit of a 
joke!

Increasingly in medicine the US is becoming a backwater.  We are in process 
with negotiating one clinical trial and have and agreement in place 
(pending regulatory approval) for another.  All these trials are "out of 
country"  and the initial marketing of the drugs and equipment will be 
outside the US.  Getting foreign patents in relevant markets is a job for a 
professional.  Even in the US, proper patent searching, citing of prior 
work and wording of the patent (especially specific claims and scope) are 
critical to having a defensible patent.

4) We are spending about 40K a month on research/infrastructure on average, 
with this amount being (hopefully) anticipated to rise by about another 
10K/mo over the next year.  This is a lot of bucks for us, and a lot of it 
is our own money.  We aren't anxious to have our intellectual property 
stolen after not only all the money spent, but all the hard, grueling work 
(I worked 16 hours every day this week). Ditto our investors who want VALUE 
for their money.  If they wanted to do charity, they could give their money 
to UNICEF, a University, zoo or to a "nonprofit" cryonics organization.

5) Many really good ideas are not patentable.  For instance, there are 
large, *very* large clinical trials published in NEMJ and other pinnacle 
medical journals showing the profoundly protective effect of 400 IU vitamin 
E supplementation in decreasing cardiovascular morbidity and mortality.  
But, vitamin E cannot be patented.  Not even a "use patent". Further, "use 
patents" or "application patents" are very weak and hard to defend.  Some 
ideas are "obvious" and yet may not be thought of by others (competitors!) 
for years, during which time you enjoy the benefit.  For instance, putting 
patients in silos underground has all sorts of wonderful adavantages which 
more than offset the cost: floor space isn't used, bullets can't be fired 
into the dewars, bombs (even nuclear weapons not detonated overhead or 
within say 20 miles) cease to be a threat, handling is easier... and on and 
on and on.  But this is NOT patentable.  Neither are many internal 
administrative tools which give you a profound edge.  Neither are some very 
clever, but alas  from a patent examiner's standpoint, technical 
innovations which are "obvious to one skilled in the art."

None of this means you can't make a financial killing by just keeping your 
mouth shut! Hard problem, huh?

6) If you look at my record, my disclosure level has been THE highest, bar 
none, in the whole history of cryonics, right up until NOW.  This is 
because I see benefits outweighing risks in most cases.

7) So EXACTLY what we are we going to do.  Well, we've been talking with 
our relevant contractors and we've arrived at the following course of 
action:

a) Once patents have been acknowledged by the patent office as having been 
received, we will disclose specifics.  So, for instance, the recent case 
report of the last CryoCare human case which BPI performed will initially 
appear with code numbers for somw proprietary drugs.  But, the techical 
report which should follow soon, in a month or two, will have full 
disclosure of almost all drugs used (patent acknowledgement will not be in 
place for at least one drug combination by that time, but most will be).

b) Most un-patentable ideas will be disclosed where they impact the 
biological condition of the patient.  A few may be held confidential, but 
only a VERY few.  Where advances do not not impact the care of the patient: 
say we find a cheaper way to get the same product, or a better way to 
handle administration or graphing or data processing which saves us a lot 
of money (and we have ;)))) we will NOT make disclosures in many, but not 
in all cases.  In some cases we'll disclose because it builds credibility 
with the public and with customers which outweighs the benefit to the 
competition.  Indeed, it builds morale; few things are as flattering as 
imitation.

c) We have set aside an "intellectual property defense fund" which includes 
very high quality free legal help and a budget in excess of $100K for 
starters.  We will tear the cohones off anybody who infringes our patents.  
We are particularly vigorous about this because it is  first of all just, 
it is how we have been treated by others with our own ideas after they have 
been stolen, and finally, because we are happy to REASONABLY negotiate 
access to patented and nonpatented technlogy.  Indeed, we have "traded" 
with Alcor for for services (like patient pod plans in exchange for design) 
or our collapsible PIB design in exchange for good quality pix of their 
excellent MALSS design.

d) Our primary (here I speak of BPI) interest is not to become a giant 
cryonics service provider.  I HATE large structures like that and I HATE 
having to work with the kind of people required in such bureaucracies!  My 
interests are to have a reasonable market share of patients so that I can 
get the clinical skills and feedback I need taking RESEARCH from the animal 
lab to the clinical setting.  This can only be done by having control over 
the clinical setting.  The best research centers have both animal and human 
facilities under the same roof.  Loma Linda and UCLA are prime examples. 
Futher, people like Bailey at Loma Linda and Buckberg at UCLA are SURGEONS 
and RESEARCHERS who go directly from lab to clinic; invaluable! However, 
you will note that Loma Linda and UCLA do not strive to treat every patient 
in the world or even in America!

My philosophy is that if I put all my efforts in trying to capture MAXIMUM 
market share of patients I am going to hurt myself in research.  On the 
other hand, if I don't first-hand confront clinical problems and have to 
deal with the costs, hassles and problems associated with the new 
technology 21CM and BPI develop, I am screwing myself badly.  Further, 
transition from animal to humans is best done by investigators skilled at 
working with BOTH.

8) The first half of the case report on the first CC patient is now 
available from CryoCare ((800)-TOP-CARE) in their most recent newsletter.  
The second half should appear shortly.  There is a fair amount of 
biomedical detail in this report even though it is not the full technical 
case report (probably 75% of it, though!).  I suggest interested people 
contact CC for copies.

9) BPI has published extensive reports on EM and other findings from canine 
cryopreservation studies.  These are available in large measure through 
this venue, and pix of accompanting EMs can be ordered at cost via BPI by 
mail only (BPI, 10743 Civic Center Drive, Rancho Cucamonga, CA 91730).

10) The best way to explore the things you want to know is to go and meet 
the investigators after first talking by phone.  Call me anytime after 1300 
PST and I'll be happy to talk with you: (909)987-3883

Mike Darwin


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