On September 3, 2019, KEI submitted a request to the NIH that it investigate an apparent failure to disclose federal funding in patents in adeno-associated viral (AAV) gene therapies. A failure to disclose federal funding is a violation of the Bayh-Dole Act (35 U.S.C. §§ 200 et seq) and if confirmed, carries several possible remedies, including the remedy that the government take title of the patents in question. The request concerns 7 patents assigned to the Trustees of the University of Pennsylvania (UPenn) that list 3 inventors: Guangping Gao, James M. Wilson, and Mauricio Alvira.
For more on KEI’s work on non-disclosure of federal funding in medical technology patents, please see: https://www.keionline.org/bayh-dole/failure-to-disclose
(Update: KEI also separately filed a request to the NIH regarding further AAV-related patents assigned to the University of Pennsylvania that failed to disclose federal funding, concerning another set of inventors, Jean Bennett, Therese Cronin, and Luk Vandenberghe.)
A PDF version of the request is available here, and the full text of the request follows below.
September 3, 2019
Ms. Michelle G. Bulls
Director
Office of Policy for Extramural Research Administration (OPERA)
National Institutes of Health
Via E-mail: MICHELLE.BULLS@NIH.GOV
Dear Ms. Bulls,
I am writing to request an investigation into apparent non-disclosure of federal funding for several patents assigned to the Trustees of the University of Pennsylvania.
KEI has been investigating federal funding of certain gene therapies. In this instance, we are writing in regards to seven patents that were issued to the same three inventors and assigned to the Trustees of the University of Pennsylvania that do not disclose federal funding.
The three inventors are:
- Gao Guang-ping,
- James M. Wilson, and
- Mauricio Alvira.
All seven patents that did not report federal funding are related to adeno-associated virus (AAV) sequences. The patent numbers, filing dates and patent titles are listed in Table 1.
Table 1: Seven patents related to AAV sequences with the same three inventors and no federal funding disclosures.
| Patent | Filing Date | Title | Inventors |
| 10,308,958 | 2017-06-27 | Method of detecting and/or identifying adeno-associated virus (AAV) sequences and isolating novel sequences identified thereby | Gao; Guangping(Westborough, MA), Wilson; James M.(Philadelphia, PA), Alvira; Mauricio R.(Philadelphia, PA) |
| 10,041,090 | 2014-12-02 | Method of detecting and/or identifying adeno-associated virus (AAV) sequences and isolating novel sequences identified thereby | Gao; Guangping(Westborough, MA), Wilson; James M.(Glen Mills, PA), Alvira; Mauricio R.(Philadelphia, PA) |
| 9,790,472 | 2012-10-03 | Method of detecting and/or identifying adeno-associated virus (AAV) sequences and isolating novel sequences identified thereby | Gao; Guangping(West Borough, MA), Wilson; James M.(Glen Mills, PA), Alvira; Mauricio R.(Philadelphia, PA) |
| 8,906,675 | 2007-11-14 | Adeno-associated virus (AAV) sequences and isolating novel sequences identified thereby | Gao; Guangping(Rosemont, PA), Wilson; James M.(Glen Mills, PA), Alvira; Mauricio R.(Philadelphia, PA) |
| 8,524,446 | 2010-12-08 | Method for detecting adeno-associated virus | Gao; Guangping(West Borough, MA), Wilson; James M(Glen Mills, PA), Alvira; Mauricio R.(Philadelphia, PA) |
| 7,235,393 | 2003-04-22 | Method for direct rescue and amplification of integrated viruses from cellular DNA of tissues | Gao; Guangping(Rosemont, PA), Wilson; James M.(Gladwyne, PA), Alvira; Mauricio R.(Philadelphia, PA) |
| 7,198,951 | 2003-07-26 | Adeno-associated virus (AAV) serotype 9 sequences, vectors containing same, and uses therefor | Gao; Guangping(Rosemont, PA), Wilson; James M.(Gladwyne, PA), Alvira; Mauricio(Philadelphia, PA) |
The seven which do not disclose federal funding in the U.S. PTO database or in the NIH RePORTER database, can be compared to the following ten patents in Table 2 that have the same three inventors and also pertain to AAV sequences, but do report federal funding in the patents.
Table 2: Ten patents relating to AAV sequences with the same three inventors and federal funding disclosures.
| Patent | Filing date | Title | Government Rights in Patent | Inventors |
| 10,301,650 | 2015-02-08 | Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor | DK047757 and HL059407 awarded by the National Institutes of Health. | Gao; Guangping, Wilson; James M., Alvira; Mauricio R. |
| 10,266,846 | 2016-10-20 | Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor | DK047757 and HL059407 awarded by the National Institutes of Health. | Gao; Guangping, Wilson; James M., Alvira; Mauricio R. |
| 9,677,089 | 2016-03-30 | Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor | P30 DK 47757-09, NIDDKD
P01 HL 59407-03 NHLBI |
Gao; Guangping, Wilson; James M., Alvira; Mauricio R. |
| 9,587,250 | 2015-01-16 | Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor | P30 DK 47757-09 NIDDKD
P01 HL 59407-03 NHLBI. |
Gao; Guangping, Wilson; James M., Alvira; Mauricio R. |
| 9,493,788 | 2015-01-16 | Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor | P30 DK 47757-09 NIDDKD
P01 HL 59407-03 NHLBI. |
Gao; Guangping, Wilson; James M., Alvira; Mauricio R. |
| 8,962,332 | 2013-09-13 | Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor | P30 DK 47757-09 NIDDKD,
P01 HL 59407-03 NHLBI |
Gao; Guangping, Wilson; James M., Alvira; Mauricio R. |
| 8,962,330 | 2007-10-31 | Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor | P30 DK 47757-09 NIDDKD
P01 HL 59407-03 NHLBI |
Gao; Guangping, Wilson; James M., Alvira; Mauricio R. |
| 8,318,480 | 2007-10-31 | Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor | P30 DK 47757-09, NIDDKD
P01 HL 59407-03, NHLBI. |
Gao; Guangping, Wilson; James M., Alvira; Mauricio R. |
| 7,790,449 | 2007-09-06 | Adeno-associated virus (AAV) serotype 8 sequences, vectors containing the same, and uses therefor | In February 19, 2019 Certificate of Correction:
DK-047757 and HL-059407 |
Gao; Guangping, Wilson; James M., Alvira; Mauricio R. |
| 7,282,199 | 2003-04-25 | Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor | In March 5, 2019 Certificate of Correction:
DK-047757 and HL-059407 |
Gao; Guangping,
Wilson; James M., Alvira; Mauricio R. |
In addition, there are three other patents that have the same title as the patents in Table 2 and have the same three inventors, plus a fourth inventor (Luk H. Vandenberghe), and which also disclose federal funding involving the same two grants.
Table 3: Three patents related to AAV sequences with the same three inventors as in Table 1 and 2, plus Luk Vandenberghe, with disclosures of federal funding.
| Patent | Filing date | Title | Government Rights in Patent | Inventors |
| 10,265,417 | 2006-08-03 | Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses therefor | P30 DK47757 NIDDK and P01 HL59407 NHLBI awarded by the National Institutes of Health. | Wilson; James M., Gao; Guangping, Alvira; Mauricio R., Vandenberghe; Luc H. |
| 9,737,618 | 2015-07-20 | Adeno-associated virus (AAV) glades, sequences, vectors containing same, and uses therefor | P30 DK47757 NIDDK and P01 HL59407 NHLBI awarded by the National Institutes of Health. | Wilson; James M., Gao; Guangping, Alvira; Mauricio R., Vandenberghe; Luk H. |
| 7,906,111 | 2004-09-30 | Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses therefor | P30 DK47757 NIDDK and P01 HL59407 NHLBI awarded by the National Institutes of Health. | Wilson; James M., Gao; Guangping , Alvira; Mauricio R. , Vandenberghe; Luc H. |
The two grants disclosed in Tables 2 and 3 covered a span of 26 years and involved more than $63 million in public funds (see Table 4).
Table 4: Two NIH grants identified on the Penn AAV patents in Tables 2 and 3.
| Funding agency | Grant # | First to last year | Cumulative NIH funding |
| NIDDK | P30 DK 047757 | 1993 to 2017 | $26,335,057 |
| NHLBI | P01 HL 059407 | 1999 to 2019 | $36,864,829 |
Also, we note that James Wilson is listed as the principal investigator for 109 projects and 90 subprojects at Penn involving $105.5 million in NIH funding from seven different NIH institutes/centers, from 1992 to 2019, indicating that public funding has played a significant role in supporting his research.
We would like to speak with you or the appropriate contact in your office about this and other related cases of non-disclosures of federal funding in patents.
Sincerely
James Love
Knowledge Ecology International
1621 Connecticut Avenue, Suite 500
Washington, DC 20009
http://keionline.org
James.Love@keionoline.org