DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Acknowledgement is made of Applicants’ claim for benefit to prior filed US Provisional Application 63/066,011, filed on 08/14/2020. This application claims the benefit of priority to Patent Application PCT/US2021/045881. Acknowledgement is made of Applicants' claim for benefit to prior filed to Patent Application Number PCT/US2021/045881, filed on 08/13/2021.
Information Disclosure Statement
The IDS filed 09/25/2023 has been considered by the Examiner.
Status of Claims
Claims 1, 7, 12-13, 19-20, 39, 41, 48, 50, 58, 62-63, 94, 142-143, 150, 166, and 177-178 are under examination.
Claim 2-6, 8-11, 14-18, 21-38, 40, 42-47, 49, 51-57, 59-61, 64-93, 95-141, 144-149, 151-165, and 167-176 are cancelled.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 7, 12-13, 19-20, 39, 41, 48, 50, 58, 62-63, 94, 142-143, 150, 166, and 177-178 are rejected under 35 U.S.C. 103 as being unpatentable over Qiu et al. (Allergy, 2019) in view of Draganov et al. (WO-2019236633-A2) as evidenced by Krivoy et al. (Current drug safety., 2008).
Regarding claim 1, Qiu discloses a (i) method of treating hereditary angioedema, HAE, in a patient in need thereof (page 1, abstract:background). Qiu et al. teach a (ii) one time treatment to provide long term protection from angioedema attacks in affected individuals (page 3, abstract:conclusion), which reads on inducing sustained remission. Qiu et al. teach (iii) the one time treatment would provide sustained circulating C1EI levels sufficient to prevent angioedema episodes (page 1, abstract:background) which would reduce the risk of recurrent angioedema episodes (iv). Qiu et al. teach the risk of (v) developing laryngeal angioedema attacks in a patient diagnosed as having HAE (page 2, introduction). Qiu et al. teach the treatment for HAE is focused on life-saving efforts, slowing the progression and severity of attacks, reducing the number of future attacks, and their impact on quality of life (page 6, discussion), which would decrease the risk of developing laryngeal angioedema attacks. Qiu et al. teach the method comprising administering to the patient a composition comprising a transgene that encodes a C1-esterase inhibitor, C1-INH, protein (1083, col 2, para 3).
Qiu et al. do not teach the composition is a population of pluripotent cells comprising a transgene.
Draganov et al. teach carrier cells and virus combinations for treating diseases (cover page, abstract). Draganov et al. teach the exemplary carrier cells administering a population of pluripotent cells comprising a transgene that encodes a therapeutic gene (page 98, lines 1-5). Draganov et al. teach viruses preferentially replicate in immune-privileged environments, but when administered as a treatment they must escape from or avoid host immune response (page 1, lines 22-26). Draganov et al. teach the viruses must avoid immune responses to ensure sufficient virus reaches the diseased cells (page 1, lines 22-26).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Qiu et al. for a method of treating HAE comprising a transgene that encodes a C1-esterase inhibitor, C1-INH, protein with the teachings of Draganov et al. for treating diseases utilizing a carrier cell. Draganov et al. provide motivation by teaching that a cell carrier provides a more suitable environment for delivery and expansion of a therapeutic vector. One of skill in the art would have had a reasonable expectation of success at combining Qiu et al. and Draganov et al. because both teach disease treatments utilizing viral vectors to deliver a therapeutic gene.
Regarding claim 7, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 1. Draganov et al. teach the pluripotent cells utilized as carrier cells could be hematopoietic stem cells (HSCs), embryonic stem cells, or induced pluripotent stem cells (page 66, lines 16-32).
Regarding claim 12, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 1. (i) Draganov et al. teach the population of pluripotent cells is administered systematically to the patient (page 93, lines 15-17). (ii) Draganov et al. teach the pluripotent cells are autologous or allogenic with respect to the patient (page 2, lines 21-30). (iii) Draganov et al. teach cells transduced ex vivo (page 61, lines 27-28). Qiu et al. and Draganov et al. make obvious the cells expressing C1-INH. Draganov et al. teach the pluripotent cells are obtained by delivering to the cells a nuclease that catalyzes a single/double strand break at a target position in the genome (page 143, lines 20-27).
Regarding claim 13, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 12. (i) Draganov et al. teach the population of pluripotent cells is administered to the patient by way of intravenous injection (page 10, lines 12-13). (ii) Draganov et al. teach the allogeneic carrier cells are HLA matched to the patient (page 28, lines 6-9). (iii) Draganov et al. teach the viral vector for cell transduction is selected from a poxviruses, herpesviruses, adenoviruses, retroviruses, rhabdoviruses, picornavirus, or parvovirus (page 37, lines 26-30). (v) Draganov et al. teach the pluripotent cells are transfected by electroporation, cell squeezing, or sonoporation (page 144, lines 25-29). (vi) Draganov et al. teach the nuclease is delivered to the cells in combination with a guide RNA (gRNA) that hybridizes to the target position within the genome of the cell (page 143, lines 11-16). (vii) Draganov et al. teach the nuclease is a clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (page 143, lines 11-16).
Regarding claim 19, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 13. (i) Draganov et al. teach the viral vector is a Retroviridae family viral vector (page 37, lines 25-27). (vi) Draganov et al. teach the pluripotent cells are obtained by delivering to the cells a nuclease that catalyzes a single/double strand break at a target position in the genome (page 143, lines 20-27).
Regarding claim 20, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 19. (i) Draganov et al. teach the Retroviridae family viral vector is a lentiviral vector (page 144, lines 7-9). (ii) Draganov et al. teach the viral vector for cell transduction is selected from a poxviruses, herpesviruses, adenoviruses, retroviruses, rhabdoviruses, picornavirus, or parvovirus (page 37, lines 26-30).
Regarding claim 39, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 19. (iii) Qiu et al. teach the viral vector that encodes the template nucleic acid is an AAV vector, which is AAV2 (page 4, AAV Vectors).
Regarding claim 41, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 39. (i) Draganov et al. teach the Retroviridae family virus is a lentiviral vector that encodes the template (page 144, lines 7-10).
Regarding claim 48, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 1. Draganov et al. teach prior to administering the population of pluripotent cells to the patient, the patient can be treated with a chemotherapeutic drugs which could be busulfan (pages 172-173, lines 24-32&1-3). Busulfan is a well-known bone marrow ablative agent, which removes a population of endogenous pluripotent cells as evidenced by Krivoy et al. (abstract). Therefore, pretreatment of the patient with busulfan as taught by Draganov et al. reads on (i) prior to administering the population of pluripotent cells to the patient, a population of endogenous pluripotent cells is ablated in the patient by administration of one or more conditioning agents to the patient; or (ii) the treating comprises ablating a population of endogenous pluripotent cells in the patient by administering to the patient one or more conditioning agents prior to administering the population of pluripotent cells to the patient.
Regarding claim 50, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 48. (page 176-177). Draganov et al. teach the pretreatment of a patient with busulfan (pages 172-173, lines 24-32&1-3), which (ii) is a conditioning agent that depletes a population bone marrow (including CD34+ cells) in the patient.
Regarding claim 58, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 1. (i) Qiu et al. teach the transgene is operably linked to a ubiquitous promoter (CAG) (page 4, AAV Vectors).(ii) Draganov et al. teach the viral promoters are substituted for tissue-specific promoters, to regulate a transgene (page 89, lines 1-5).
Regarding claim 62, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 1. (i) Qiu et al. teach a transgene operably linked to an enhancer (page 4, AAV Vectors). (iii) Qiu et al. teach the patient is a mouse, which is a mammal (page 3, Generation of a C1 El Deficient Murine Model). Draganov et al. further teach mammalian patients and cells (pages 24&25, lines 25&9). (iv) Qiu et al. teach the patient has a rare autosomal dominant disorder resulting from mutations in the C1-inhibitor gene (page 6, Discussion). (v) Qiu et al. teach the patient has a mutation in a gene encoding C1-INH that causes (b) expression of a truncated transcript (page 4, Generation of a C1 El Deficient Murine model). (xii) Qiu et al. and Draganov make obvious treatment with pluripotent cells. Qiu et al. teach a (ii) one time treatment to provide long term protection from angioedema attacks in affected individuals (page 3, abstract:conclusion); which reads on inducing sustained remission. (xv). Qiu et al. and Draganov et al. make obvious administration of pluripotent cells to the patient. Qiu et al. teach the risk of (v) developing laryngeal angioedema attacks in a patient diagnosed as having HAE (page 2, introduction). Qiu et al. teach the treatment for HAE is focused on life-saving efforts, slowing the progression and severity of attacks, reducing the number of future attacks, and their impact on quality of life (page 6, discussion); which would decrease the risk of developing laryngeal angioedema attacks.
Regarding claim 63, Qiu et al. and Draganov et al. make obvious the method as described above in regard to claim 62. (iii) Qiu et al. teach the patient is a mouse which is a mammal (page 3, Generation of a C1EI Deficient Murine Model).
Regarding claim 94, Qiu et al. discloses a (i) method of treating hereditary angioedema, HAE, in a patient in need thereof (page 1, abstract:background). Qiu et al. teach a (ii) one time treatment to provide long term protection from angioedema attacks in affected individuals (page 3, abstract:conclusion), which reads on inducing sustained remission. Qiu et al. teach (iii) the one time treatment would provide sustained circulating C1EI levels sufficient to prevent angioedema episodes (page 1, abstract:background); which would reduce the risk of recurrent angioedema episodes (iv). Qiu et al. teach there is a risk of (v) developing laryngeal angioedema attacks in a patient diagnosed as having HAE (page 2, introduction). Qiu et al. teach the treatment for HAE is focused on life-saving efforts, slowing the progression and severity of attacks, reducing the number of future attacks, and their impact on quality of life (page 6, discussion); which would decrease the risk of developing laryngeal angioedema attacks. Qiu et al. teach a method of administering to the patient a composition comprising a transgene that encodes a C1-esterase inhibitor, C1-INH protein (1083, col 2, para 3).
Qiu et al. does not teach the viral vector is a lentiviral vector. However, it would have been obvious to one of ordinary skill in the art to make the substitution of the AAV viral vector for a lentiviral vector. Draganov et al. teach cells as carriers for a therapeutic viruses (page 38 lines 3-5), which could be adeno-associated viruses (AAV) or lentiviruses. Therefore, the results of exchanging one virus for another would be expected.
Regarding claim 142, Qiu et al. discloses a treatment for hereditary angioedema, HAE, in a patient in need thereof (page 1, abstract:background). Qiu et al. teach administration of an adeno-associated virus (AAV) gene transfer vector expressing the genetic sequence of the normal human Cl esterase-inhibitor (abstract:background).
Qiu et al. do not teach the composition is a population of pluripotent cells comprising a transgene.
Draganov et al. teach compositions comprising carrier cells and virus combinations for treatment of cancers (cover page, abstract). Draganov et al. teach the exemplary carrier cells administering a population of pluripotent cells comprising a transgene that encodes a therapeutic gene (page 98, lines 1-5). Draganov et al. teach viruses are protected from the host's immune responses when delivered in a cell to further improve the survivability of the vector virus (page 1, lines 22-26). Draganov et al. further teach a composition containing at least one active pharmaceutical or therapeutic agent and one or more excipients (page 54, lines 4-5).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Qiu et al. for treating HAE comprising a transgene that encodes a C1-esterase inhibitor with the teachings of Draganov et al. for treating diseases utilizing a carrier cell. Draganov et al. provide motivation by teaching that a cell carrier provides a more suitable environment for delivery and expansion of a therapeutic vector. One of skill in the art would have had a reasonable expectation of success at combining Qiu et al. and Draganov et al. because both teach disease treatments utilizing viral vectors to deliver a therapeutic agent. Therefore, Qiu et al. and Draganov et al. make obvious a pharmaceutical composition comprising;(a) (i) a population of pluripotent cells comprising a transgene that encodes a C1-INH protein and (ii) one or more carriers
Regarding claim 143, Qiu et al. and Draganov et al. make obvious the pharmaceutical composition as described above in regard to claim 142. (i) Draganov et al. teach the patient can be human (page 157, lines 8-9). Draganov et al. further teach the cells are autologous, which means they are derived from the human patient and therefore are human cells (pages 56&195, lines 5-7&7-8). (iii) Draganov et al. teach the pharmaceutical composition could be formulated for administration to a human patient (pages 52 and 242, lines 16-17& claim 1). (iv) Qiu et al. teach the transgene is operably linked to a ubiquitous promoter (CAG) (page 4, AAV Vectors). (v) Qiu et al. teach a transgene operably linked to an enhancer (page 4, AAV Vectors).
Regarding claim 150, Qiu et al. and Draganov et al. make obvious the pharmaceutical composition as described above in regard to claim 143. (i) Draganov et al. teach the composition is formulated for intravenous injection (page 150, lines 8-10) into the human patient (page 157, lines 24-30). (ii) Draganov et al. teach the pluripotent cells are autologous or allogenic with respect to the patient (page 2, lines 21-30).
Regarding claim 166, Qiu et al. and Draganov et al. make obvious the pharmaceutical composition as described above in regard to claim 150. Draganov et al. teach cells as a carrier for therapeutic viruses (page 38 lines 3-5). Draganov et al teach the therapeutic viruses could be adeno-associated viruses (AAV), Vesicular stomatitis virus (VSV), or lentiviruses (page 37, lines 25-30). Draganov et al. teach the Vesicular stomatitis virus (VSV) genome includes a glycoprotein (G) (page 85, lines 17-20). Draganov et al. further teach VSV is transmitted by insect vectors and the disease is limited to its natural hosts, including horses, cattle and pigs, with mild and asymptomatic infection in humans (page 85, lines 22-25). These factors and there is generally no pre-existing human immunity to VSV make it a good candidate as a vector (page 86, lines 2-4). Draganov et al. teach the modified VSV-GP does not elicit a detectable neutralizing antibody response, and that the genetically modified oncolytic virus was insensitive to human complement, remaining stable over the length of the experiment (page 86, lines 28-31)
Therefore, one of ordinary skill in the art would have been motivated to combine the teachings of a lentiviral vector with the teachings of a VSV-G envelope protein. Draganov et al. provide motivation by teaching VSV-G can infect human cells with stability throughout treatment by not invoking an immune response. There would be a reasonable expectation of success because the chimeric virus would be more stable and would not be prematurely cleared from the patient by an immune response.
Regarding claim 177, Qiu et al. and Draganov et al. make obvious the pharmaceutical composition as described above in regard to claim 142. Draganov et al. teach the pharmaceutical composition can be included in a kit (page 170, lines 9-12).
Regarding claim 178, Qiu et al. and Draganov et al. make obvious the kit as described above in regard to claim 177. Draganov et al. teach a kit can contain instructions (page 169, lines 21-27). Qiu et al. and Draganov make obvious the kit would include instructions for (i) method of treating hereditary angioedema, HAE, in a patient in need thereof (page 1, abstract:background); (ii) one time treatment to provide long term protection from angioedema attacks in affected individuals (page 3, abstract:conclusion), which reads on inducing sustained remission; (iii) the one time treatment would provide sustained circulating C1EI levels sufficient to prevent angioedema episodes (page 1, abstract:background); which would reduce the risk of recurrent angioedema episodes (iv); (v) developing laryngeal angioedema attacks in a patient diagnosed as having HAE (page 2, introduction); a treatment for HAE is focused on life-saving efforts, slowing the progression and severity of attacks, reducing the number of future attacks, and their impact on quality of life (page 6, discussion), which would decrease the risk of developing laryngeal angioedema attacks; the method comprising administering to the patient a composition comprising a transgene that encodes a C1-esterase inhibitor, C1-INH, protein (1083, col 2, para 3).
Conclusion
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/C.L.M./Examiner, Art Unit 1638
/Anna Skibinsky/
Primary Examiner, AU 1635