DETAILED ACTION
Claims 1-21 are currently pending.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Objections
Claim 1 is objected to because of the following informalities: typographical.
Claim 1 recites the abbreviation “ANC” (absolute neutrophil count), which should be spelled out at the first use in a claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claims 1, 9, and 17, all limit the pooled sample of cells to a pool wherein one sample in the pool matches the patient at 3/6, 4/6, 5/6, or 6/6 HLA antigens and all other samples in the pool have not been HLA matched to the patient. There is no support in the specification for a pool containing both these specific partially to fully matched cells and unmatched cells. This is a new matter rejection.
Since claims 2-8, 10-16 and 18-21 depend from claims 1, 9, and 17, they also are rejected for containing new matter.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1-21 are rejected under pre-AIA 35 U.S.C. 103(a) as obvious over Delaney et al (2008, Blood (ASH Annu Meet Abstr) 2008; 112: Abstract 212; see PTO-892) (“Delaney”), in view of Lister et al (2007, Stem Cells and Development, 16: 177-186; see PTO-892) (“Lister”), Advania et at (2009, Current Opinion in Hematology, 16(2): 124-128; see PTO-892)(“Advania”) and Croop et at (2000, Bone Marrow Transplantation, 26: 1271-1279; see PTO-892) (“Croop”).
Regarding claims 1, 9, and 17, Delaney teaches of methods of performing an umbilical cord blood transplant (UCBT) in six patients wherein the patients also received pooled cord blood (CB) stem and progenitor cells that were cultured in the presence of the Notch agonist Delta 1, used for promoting the expansion of the CD34+ enriched cell population. Delaney notes that delayed hematopoietic recovery following cord blood transplantation (CBT) is thought to result from inadequate numbers of progenitor cells in the graft and is associated with increased early transplant-related morbidity and mortality. Regarding claims 1, 7, 9, 12 and 17, Delaney teaches ex vivo expansion in the presence of the Notch agonist, Delta 1, greatly increased the population of the human CD34 progenitor cells, and that no T cells were generated during culture. Regarding claims 1, 9, and 17, Delaney teaches patients were administered a first treatment of non-cultured CB unit and then administered a second unit of CD34 enriched and cultured stem and progenitor cells. Regarding claims 1, 9, and 17, Delaney teaches CB units were selected on the basis of cell dose and a requirement of matching at least 4 of 6 HLA loci with the patient (i.e., no more than 2 HLA antigen mismatches), and that the cultured cells were a 4/6 and 5/6 match to the patients. Regarding claims 1 and 17, Delaney teaches that patients achieved ANC>500 following treatment. Regarding claims 4-5 and 13-14, Delaney teaches that the early engraftment was from the CD34 cultured cells whereas the non-cultured CB unit provided longer term engraftment. Regarding claims 1, 3, 11, 17, and 20, Delaney also teaches that patients can be treated with 2 non-cultured CB units.
Delaney does not teach pooling units such that Delaney’s mismatched expanded cells are combined with cells that have not been HLA matched (claims 1, 9, and 17). Delaney does not teach the samples are taken from different donors (claims 3, 11, and 20). Delaney does not teach explicitly teach depleting of T cells (claims 1, 9, and 17). Delaney does not teach doses of at least 75 million CD34+ cells (claims 8, 16, and 21). Delaney does not teach using the treatment for a patient that has pancytopenia or neutropenia, who is undergoing treatment (claims 1, 6, 9, 15, and 17). Delaney does not teach conducting a second engraftment (claims 56, 64, and 72).
Regarding claims 1, 9, and 17, Lister is directed to multiple-unit umbilical cord blood transplantation in the setting of severe HLA mismatch (Abstract). Lister teaches administering human CD34+ cord blood stem cells to human patients without pretransplant HLA-typing (see col. 1 on page 179). Regarding claims 1, 9, and 17, Lister teaches the patients received multiple different units of cells (see col. 1, on pages 178 and 179).
Regarding claims 1, 9, and 17, Advania is directed to umbilical cord transplantation of acute myeloid leukemia (Purpose of review, page 124). Advania teaches that finding a match umbilical cord blood donor for patients with acute myeloid leukemia often takes 3 – 4 months, and ultimately, only 30–40% of patients are able to find a suitable unrelated adult donor, and one-third of donors are not available at the time they are needed. Advania continues explaining that for patients of particular racial/ethnic minorities, the chances of finding a suitable donor are even lower, and Advania concludes that this limits the usefulness of using a method comprising finding a matched donor for treatment as the disease recurs in a short time if remission is not achieved (page 124 at “Umbilical cord blood transplant for acute myeloid leukemia”). Regarding claims 1, 9, and 17, Advania teaches that HLA-typing in UCBT is unlike the high resolution typing that is critical in the case of unrelated adult donor transplants, retrospective studies demonstrate no advantage to high resolution typing for UCBT; the decreased incidence of graft-versus-host disease (GVHD) with UCBT despite HLA mismatch may be attributable in part to the immaturity and lower number of immunocompetent donor T cells (page 124 at “Umbilical cord blood transplant for acute myeloid leukemia”). Regarding claims 1, 3, 9, 11, 17, and 19-20, Advania teaches that the transplanted cells can be from one cord or from multiple cords (see col. 1 on page 127). Regarding claims 1, 6, 9, 15, and 17, Advania teaches improved neutrophil engraftment with UCB grafts, and that approximately 200 transplants have been performed in the myelobalative and NMA setting (see col. 1 on page 127). Regarding claims 2-3, 10-11, 18, and 20, Advania teaches that cells from different cords can be combined to help increase cell numbers, and that relapse rate may be lower in patients receiving a double UCBT because of the increased HLA antigen mismatch (see col. 1 on page 127).
Regarding claims 1, 9, and 17, Croop teaches a method of isolating CD34+ cells to be used in transplantation using the Isolex 300i cell separator to deplete of T cells (CD3+ cells) (see page 1277). Regarding claims 8, 16, and 21, Croop teaches the mean number of CD34+ cells isolated for transplantation was
1.9
*
10
8
(see abstract).
A person of ordinary skill in the art would have had a reasonable expectation of success in treating Delaney’s patient with Delaney’s cells pooled with cells that have not been HLA matched and have been pooled because both Lister and Advania teach patients can be treated with mismatched HLA cells, and that patients can receive cells from more than one donor.
The skilled artisan would have been motivated to treat Delaney’s patient using cells that are pooled with mismatched HLA cells because Advania teaches combining (pooling) cord cells help increase cell number, and the increased HLA antigen mismatch may help increase engraftment. Additionally, Delaney specifically teaches using unmatched units. Advania states that this problem of matching donors limits the usefulness of using a method comprising finding a matched donor for treatment as the disease recurs in a short time if remission is not achieved. Additionally, the references teach that more than one unit can be administered to patients, so pooling the cells prior to administration would increase cell number, simplify the expansion step as the samples would not need to remain separated, and the increased HLA antigen mismatch is beneficial for increasing engraftment.
A person of ordinary skill in the art would have had a reasonable expectation of success in treating Delaney’s patient with increased numbers of expanded T cell depleted CD34+ cells because Croop provides methods for obtaining a large dose of T cell depleted CD34+ cells for transplant and Advania teaches the benefits of large doses and T cell depleted CD34+ cells for transplantation. The skilled artisan would have been motivated to treat Delaney’s patient with increased numbers of expanded T cell depleted CD34+ cells method because Advania teaches ex-vivo expansion is used to increase the number of cells for transplantation and that the decreased incidence of GVHD with UCBT despite HLA mismatch may be attributable in part to the immaturity and lower number of immunocompetent donor T cells.
A person of ordinary skill in the art would have had a reasonable expectation of success in using Delaney’s treatment in view of Advania and Croop to treat a patient with neutropenia undergoing myeloablative regimen because Advania treats UBCT has been shown to increase neutrophil engraftment in myeloablative settings. The skilled artisan would have been motivated to modify Delaney’s treatment, in view of Advania and Croop, to treat a patient with neutropenia undergoing myeloablative regimen because Advania establishes the benefits of such a treatment.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Conclusion
No claims are allowed. No claims are free of prior art.
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E. YVONNE PYLA
Primary Examiner
Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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