[Ip-health] KEI and UACT Joint Comments to the NIH Regarding Exclusive License to Syncopation for CAR Therapy

James Love james.love at keionline.org
Fri Jul 16 07:33:24 PDT 2021


https://www.keionline.org/36436

KEI and UACT Joint Comments to the NIH Regarding Exclusive License to
Syncopation for CAR Therapy
July 13, 2021

Knowledge Ecology International (KEI) and the Union for Affordable Cancer
Treatment (UACT) submitted comments to the National Institutes of Health
(NIH) on Friday July 9, 2021 regarding the “Prospective Grant of an
Exclusive Patent License: Development and Commercialization of Monospecific
CD22 Chimeric Antigen Receptor (CAR) Therapies for the Treatment of B-Cell
Malignancies” (86 FR 33326) to Syncopation Life Sciences Inc. (Syncopation).

The technology is to be licensed on a worldwide basis, for the
“development, manufacture and commercialization of chimeric antigen
receptor T cell (CAR-T) immunotherapies (both autologous and allogeneically
derived) for the treatment of B cell malignancies that express
CD22…CD22-targeting CAR-T has shown early promise in clinical trials for
ALL [acute lymphoblastic leukemia] and NHL [Non-Hodgkin’s lymphoma].”

Syncopation was incorporated in California only two months ago, in May
2021. Among the three founders listed is Nancy Goodman, who is better known
to some for her charity Kids v Cancer, and her role in lobbying for the
pediatric priority review voucher, and Dr. Crystal Mackall, a well known
scientist from Stanford University. Among the investors are two venture
capital firms and the Emerson Collective, which is affiliated with Laurene
Powell Jobs. The technology being licensed is already being tested in an
NIH-run clinical trial. The comments challenge the need for exclusive
rights in patents, given the NIH investment in clinical trials, the
non-patent exclusivities (test data, orphan drug) and incentives (the FDA
pediatric priority review voucher). The comments also address safeguards
that would be appropriate if an exclusive license is granted, on topics
such as transparency, pricing, access and the term of exclusivity. Note
that in this case, the US government already owns the rights to the
inventions, test data and know-how and access to cell lines.

The joint comments follow:

------------------------------

Jim Knabb
Senior Technology Transfer Manager
NCI Technology Transfer Center
National Cancer Institute
National Institutes of Health
Email: jim.knabb at nih.gov

July 9, 2021

Re: Prospective Grant of an Exclusive Patent License: Development and
Commercialization of Monospecific CD22 Chimeric Antigen Receptor (CAR)
Therapies for the Treatment of B-Cell Malignancies (86 FR 33326)

Dear Jim Knabb:

Knowledge Ecology International (KEI) and the Union for Affordable Cancer
Treatment (UACT) offer the following comments regarding the “Prospective
Grant of an Exclusive Patent License: Development and Commercialization of
Monospecific CD22 Chimeric Antigen Receptor (CAR) Therapies for the
Treatment of B-Cell Malignancies” (86 FR 33326) to Syncopation Life
Sciences Inc., (Syncopation), which is located in Palo Alto, California
(website: https://syncopationlife.com).

Why the NIH would make this license exclusive, at least for the proposed
field of use, which includes a CAR T that is already in clinical trials,
and according to notice, “has shown early promise in clinical trials for
ALL and NHL” is not obvious.

The NIH funded and controls the inventions and the know-how to provide a
CAR T treatment that is already in a trial with a projected enrollment
comparable to or larger than all but one of the current FDA approved CAR T
treatments.

The NIH seems to currently have the ability to register the CAR Treatment
in trial NCT02315612, “Anti-CD22 Chimeric Receptor T Cells in Pediatric and
Young Adults With Recurrent or Refractory CD22-expressing B Cell
Malignancies,” and (1) avoid the granting to one company of seven years of
exclusivity under the Orphan Drug Act, (2) avoid privatizing 12 years of
exclusive rights in regulatory test data, (3) avoid granting a priority
review voucher to distort regulatory approvals, and (4) could provide
technology transfer and open licensing of the inventions throughout the
world, making the treatment a global public good.

Instead, the NIH is proposing to privatize its inventions and the potential
orphan and test data rights, so that a single firm has a global monopoly on
a promising treatment for pediatric cancers, knowing that every other CAR T
treatment has been priced from $373,000 to $438,000, with massive global
inequality of access.

In the present case, the NIH has an applicant that includes as one of its
founders, Nancy Goodman, who is best known for her efforts to lobby the US
Congress to create a pediatric priority review voucher. Now Goodman and her
colleagues stand to be beneficiaries of the waivers, which have in recent
years traded for approximately $100 million, if the applicants are
successful in registering the treatment, even if this is based upon the
evidence from the NIH funded run trial.

The Federal Register notice does not provide the rationale for the granting
of exclusive patent rights. Even if the NIH wants Syncopation to have
incentives to invest in the further commercialization of the NIH’s CAR T
treatment, to grant exclusive rights in patents, let alone life of patent
terms and global rights is not required. Even without exclusive rights to
the patents or the regulatory test data, Syncopation would earn a valuable
pediatric priority review voucher (a fact well known to Nancy Goodman and
everyone else developing similar treatments), worth perhaps $100 million,
and seven years of exclusive rights under the Orphan Drug Act, not to
mention even longer orphan exclusivities in the European Union.

If the NIH decides to give exclusive rights in the NIH’s patented
inventions and/or the NIH’s regulatory test data, surely the NIH has ample
leverage to obtain terms that limit the negative impacts of a legal
monopoly on a cancer treatment. At least two persons/entities involved in
Syncopation should be open to provisions which provide protections to the
public as regards pricing and access. Nancy Goodman comes to the company
from a non-profit patient advocacy charity. One of the three listed
investors, Emerson Collective works with Laurene Powell Jobs, and includes
in its mission impact investing, philanthropy and advocacy, “in pursuit of
a more equal and just America.” If the NIH is not exploring ways to protect
access and affordability in the licenses, it is because the NIH is
indifferent to vast inequality of access globally or the costs its actions
impose on health systems and families.

      Discussion

Syncopation was incorporated in California only two months ago, in May
2021. Among the three founders listed is Nancy Goodman, who is better known
to some for her charity Kids v Cancer, and her role in lobbying for the
pediatric priority review voucher. She is married to Michael Froman, the
former United States Trade Representative. The other two founders of
Syncopation are two Stanford scientists, Crystal Mackall, and Robbie
Majzner. Mackall is listed as the principal investigator in $52 million of
NIH/NCI grants.

The technology is to be licensed on a worldwide basis, for the:


-------begin quote
“Development, manufacture and commercialization of chimeric antigen
receptor T cell (CAR-T) immunotherapies (both autologous and allogeneically
derived) for the treatment of B cell malignancies that express CD22 wherein:

1. The T cells are engineered to be monospecific for CD22; and

2. The chimeric antigen receptor is specific for CD22 via the m971 scFv”.
-------end quote

This technology discloses CAR therapies that target CD22 by utilizing the
anti-CD22 binder known as m971. CD22 is expressed on the surface of B cells
in B cell malignancies and CD22-targeting CAR-T has shown early promise in
clinical trials for ALL [acute lymphoblastic leukemia] and NHL
[Non-Hodgkin’s lymphoma].”

The investors in the company include three firms: Samsara Biocapital, Red
Tree Venture Capital, and Emerson Collective. Emerson Collective works with
Laurene Powell Jobs, and includes in its mission impact investing,
philanthropy and advocacy, “in pursuit of a more equal and just America.”

We have previously expressed our concerns to Nancy Goodman about the lack
of access to the new cell therapies in developing countries, in the context
of our opposition to the January 2020 proposed exclusive license for a
similar technology to CJ Healthcare, (“CJ”) (86 FR 33326;
https://www.keionline.org/32158). At the time, Goodman was considering a
competing license proposal, and we asked if she would agree to any
limitations on the geographic scope of the licenses in lower income
countries, or on price discrimination against U.S. residents. At the time
we did not have an answer to those questions, but today, these are issues
that need to be raised and some questions answered.

As noted in the Federal Register notice, the technology to be licensed has
already entered into clinical trials by the NIH for two possible
indications (ALL and NHL). It is our understanding that this includes trial
NCT02315612, Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young
Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies.
The trial has a projected enrollment of 208 participants and is funded by
U.S. taxpayers. For context, consider the following.

* The safety and efficacy of Kymriah were demonstrated in one multicenter
clinical trial of 63 pediatric and young adult patients with relapsed or
refractory B-cell precursor ALL.

* For Yescarta, the primary efficacy analysis involved 81 patients.

* The clinical review team’s recommendation for accelerated approval of
Tecartus for the treatment of adults with relapsed or refractory (r/r)
mantle cell lymphoma (MCL) is based on the clinical study ZUMA-2, which
included 82 patients.

* Breyanzi’s approval was based upon evidence from 268 treated patients.

* The approval of Abecma was based upon evidence from 140 enrolled patients.

We ask the NIH to consider several measures in an exclusive license to
protect the public interest.


       Ensuring global access

Given the vast global inequality in access to cell therapies, the NIH
should ensure that the exclusive license does not extend to countries with
a per capita income less than 30 percent of the United States, in order to
ensure that the patents do not lead to restricted and unequal access in
developing countries. If the NIH rejects this suggestion, it needs to
provide something that will give effect to the policy objective in the
“United States Public Health Service Technology Transfer Policy Manual,
Chapter No. 300, PHS Licensing Policy,” which states the following: “PHS
seeks to promote commercial development of inventions in a way that
provides broad accessibility for developing countries.”

Prohibition against prices that discriminate against US residents

Any license should ensure that U.S. residents are not asked to pay prices
that exceed the median price from the seven economies of the largest GDP
and at least 50 percent of U.S. per capita income. The per capita income
can be based upon the World Bank’s Atlas method.

      Transparency

Transparency of R&D outlays. The licensees should be required to file an
annual report to the NIH, available to the public, on the research and
development (R&D) costs associated with the development of any product or
service that uses the inventions, including reporting separately and
individually the outlays on each clinical trial. We note that this is not a
request to see a company business plan or license application. We are
asking that going forward Syncopation be required to report on actual R&D
outlays to develop the subject inventions. Reporting on actual R&D outlays
is important for determining if the NIH is meeting the requirements of 35
U.S.C. § 209, that “the proposed scope of exclusivity is not greater than
reasonably necessary to provide the incentive for bringing the invention to
practical application[.]” Specifically, having data on actual R&D outlays
on each clinical trial used to obtain FDA approval provides evidence that
is highly relevant to estimating the risk adjusted costs of bringing NIH
licensed inventions to practical application.

Acknowledgement of federal funding – publication and publicity. The
licensees should be required to include, when issuing statements, press
releases, and other documents describing the development of any product
that includes the licensed inventions, a statement that describes the role
of the licensed inventions and the total and proportionate contribution of
federal funding to the research and development performed to bring the
inventions to market.

Additional transparency issues. The license should have provisions that
give effect to the transparency norms set out in WHA72.8 “Improving the
transparency of markets for medicines, vaccines, and other health
products”, a resolution enthusiastically supported by HHS in 2019.

      Additional Provisions to Protect the Public Interest

Global registration and affordability. The licenses should require the
licensee to disclose the steps that each will take to enable the timely
registration and availability of the medical technology at an affordable
price in the United States and in every country with a demonstrated need,
according to the Centers for Disease Control and Prevention (CDC) and/or
the World Health Organization (WHO), either by supplying a country directly
at an affordable, publicly disclosed price and with sufficient quantities,
or by providing technology transfer and rights to all intellectual property
necessary for third parties to do so.

Medicines Patent Pool. The NIH should retain a right to grant the WHO, the
Medicines Patent Pool or other governments the rights to use the patent
rights to procure the medical technology from competitive suppliers,
including technology transfer, in LMICs, upon a finding by HHS or the WHO
that people in these markets do not have sufficient access to the medical
technology.

      Conclusion

In the event that the NIH grants an exclusive license, the restrictions and
safeguards in 35 USC 209 are intended to protect the public. The NIH needs
to demonstrate that the license includes measures to insure transparency
and access, and avoids unnecessary fiscal toxicity.

Please notify us if and when a license is granted, so we can request a copy
under the Freedom of Information Act.

Sincerely,

Knowledge Ecology International
Union for Affordable Cancer Treatment


-- 
James Love.  Knowledge Ecology International
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