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 .
Status of the Claims
Claims 1-16, 24, 36, 48, and 49 are pending.
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 10, 12, and 14 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 10, the term “neuroprotective molecule or growth factor” is not defined by the claim, and the specification does not provide a limiting definition of what qualifies as a “neuroprotective molecule or growth factor” and what does not. Thus, the disclosure does not reasonably convey to the skilled artisan that the inventor had possession of the claimed engineered cell that expressed effectively any molecule with any neuroprotective properties or any growth factor, the features which are undefined.
For purposes of examination, the scope of the term “neuroprotective molecule or growth factor” was limited to the list of example molecules given in paragraph [0099] in the specification.
Regarding claim 12, the term “chemotactic receptor” is not defined by the claim, and the specification does not provide a limiting definition of what qualifies as a “chemotactic receptor” and what does not. Thus, the disclosure does not reasonably convey to the skilled artisan that the inventor had possession of the claimed engineered cell that expressed effectively any receptor that may act as a chemotactic receptor, the features which are undefined.
For purposes of examination, the scope of the term “chemotactic receptor” is limited to the examples given in the specification, CCR2, CCR3, CXCR2 or CXCR3. (Spec. [0100])
Regarding claim 14, the term “anti-apoptotic molecule” is not defined by the claim, and the specification does not provide a limiting definition of what qualifies as a “anti-apoptotic molecule” and what does not. Thus, the disclosure does not reasonably convey to the skilled artisan that the inventor had possession of the claimed engineered cell that expressed effectively any molecule that could be considered in any degree to be an anti-apoptotic molecule, the features which are undefined.
For purposes of examination, the scope of the term “chemotactic receptor” is limited to the examples given in the specification, CCR2, CCR3, CXCR2 or CXCR3. (Spec. [0100])
For purposes of examination, the scope of the term “anti-apoptotic molecule” is limited to the examples given in the specification, BCL2L2, BCL-XL, MCL-1, BFL-1, BCL-W, or BCL2L10. (Spec. [0101])
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 10, 12, and 14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “a reference control” in claims 10, 12, and 14 is a relative term which renders the claim indefinite. The term “a reference control” is defined in the spec as ‘a level detected in a subject in general or a study population.’ (Spec. [0102]). However, even with this definition, in terms of claims 10, 12, and 14 it is still unclear what qualifies as a “a reference control” and what does not. A subject in general or a study population is not referred to in these claims, and if it were, would a subject in general refer to a healthy subject? Is a study population a population of cells, or subjects? Is the subject in general suffering from a certain disease? If so, which disease? Does a study population refer to a population of subjects, or does this refer to a population of CD33+ cells, or CD33- cells?
Is it necessary that the reference cell is derived from the same subject, source, or even the same sample as the claimed engineered cell? It is unclear what would necessarily qualify as a control based on the claim language. Thus, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention as it is unclear what the level of expression in the claimed engineered cell should be compared to.
Claims 10, 12, and 14, the claims only require that the engineered cell has a claimed phenotype (CD33+) and in increased expression of the claimed molecule, and not that the cell from which the engineered cell is derived has that phenotype or expresses that molecule in the first place, or even that the reference cell is the same type of cell as the cell from which the engineered cell is derived. In effect, “a reference control” is so broad that this means that any level of expression of the claimed molecule in any cell would read on these “enhanced expression as compared to a reference control” claims. For purposes of examination, any naturally occuring cell is considered to read on “a reference control”. For purposes of examination, any level of expression of the claimed molecules in the engineered cell reads on claims 10, 12, and 14.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Kim
Claim 1-3 and 10-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Kim (US20180216065A1) (Provided in IDS of 5/29/2024)
As evidenced by Parrinello (Parrinello et al., Myeloid-Derived Suppressor Cells in Patients with Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance., Blood Volume 114, Issue 22, 2009, Page 4890).
Regarding claim 1 and 16, Kim teaches a method of culturing cord derived CD34+ cells in the presence of GM-CSF/SCF or G-CSF/SCF to induce differentiation into Myeloid-Derived Suppressor Cells (MDSCs) and proliferate the resulting MDSCs (Kim claim 5). Kim teaches that the resulting MDSC has a phenotype including CD33+ (Kim, claim 12, claim 14, [0036]). According to the specification, the term “engineered cell” refers to a cell modified by means of genetic engineering, or polarization with, for example, soluble factors and/or ligands, or isolated cells with characteristics differing from any naturally occurring cell (Specification [0088]). In this case, Kim polarizes cord derived CD34+ cells with GM-SCF and SCF, which are reasonably considered to be soluble factors and/or ligands. So, Kim also teaches an engineered cell with a phenotype of CD33+.
Regarding claim 2, Kim teaches culturing cord blood derived CD34+ cells with GM-CSF (100 ng/mL) and SCF (50 ng/mL) for 3 weeks, resulting in Differentiation-Induced MDSCs with a phenotype of CD11b+CD33+. Kim does not measure the CD34 expression level of their resulting MDSCs, so it is not immediately clear from Kim’s disclosure if the resulting cell is still CD34+, a lower but still detectable level of CD34 marker on their surfaces (CD34dim) or are totally CD34-.
However, Kim does teach that Myeloid-derived suppressor cells are defined as CD11b+Gr1+ cells in mice and as Lin-HLA-DR-CD11b+CD33+ in humans. Kim teaches that these cells are a very heterogeneous (composed of several different types) myeloid cell population, and they are one type of the precursors of hematopoietic stem cells, which develop macrophages, dendritic cells, and granulocytes at various stages of hematopoietic differentiation. (Kim [0003]).
Regarding the limitation the engineered cells are both CD34+ and CD33+, Parrinello teaches that Human MDSC have an immature phenotype, including lineage negative (Lin-), CD14-, HLA-DR-, CD15+, CD34+, CD11b+, CD33+, and CD13+ cells. (Parrinello, Abstract).
As discussed in MPEP § 2112, citing In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594), the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case, there is reason to believe that at least some of Kim’s MDSC are also CD34+, since Kim teaches that their MDSC are defined as being Lin-, HLA-DR-, CD11b+, and CD33+. Kim further teaches that MDSC generally are a heterogenous precursor cell population. Kim does not happen to test their MDSC for the presence or absence of CD34. Parrinello then teaches that at least some MDSC are also CD34+ in addition to the phenotypical markers listed by Kim. It is reasonable that in Kim’s heterogenous population of MDSC, at least some of them will also be in the appropriate state of differentiation to either be CD34+, or at least still retain enough CD34 activity to be considered CD34dim.
Regarding claim 3, Kim teaches that the CD34+ cells from which are isolated from human cord blood. (Kim, Claim 2, 5, 14)
Regarding claim 10 and 11, Kim teaches that it was observed that MDSCs induced by the combination of GM-CSF/SCF showed a significant increase in the secretion of IL-10 when stimulated with CD40 antibodies, and large amounts of VEFG and TGF-β were secreted without being affected by whether or not stimulated with the CD40 antibodies. (Kim [0045])
Regarding claim 12 and 13, Kim teaches that the myeloid-derived suppressor cells may express PDL-1, CCR2, CCR5, CD62L, CXCR4, and ICAM-1 as cell surface markers. (Kim [0042]).
Regarding claim 14 and 15, Kim does not measure BCL2L2 expression in their resulting MDSC cells. However, Kim does teach contacting a stem cell (CD34+ cord blood cell) with G-CSF and SCF to create an engineered CD33+ cell. (Kim, [0036]). The specification discloses that in some embodiments, the engineered cell is a primary or engineered human umbilical cord blood (HUCB) cell. (Spec. [0006]). In some embodiments, the engineered cell is expanded in vitro in a cell culture medium prior to administration. In some embodiments, the medium comprises recombinant human stem cell factor (SCF), thrombopoietin, G-CSF, IL-4, TGFβ, or GM-CSF or a combination thereof. That is, the specification discloses that in one envisioned embodiment, the claimed engineered cell may be contacted with G-CSF and SCF, which is the same combination taught by Kim.
As discussed in MPEP § 2112, citing In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594), the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case, there is reason to believe that Kim’s engineered cell, which was exposed to G-CSF and SCF, expresses BCL2L2, since a disclosed method of generating Kim’s cell that expresses BCL2L2 is identical Kim’s method. Since the claimed method is identical to the method disclosed by Kim, Kim’s cells are reasonably expected to generally have the same or at least similar expression phenotype to the claimed cell.
McNiece
Claim 1 and 4-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
McNiece et al., Action of Interleukin-3, G-CSF, and GM-CSF on Highly Enriched Human Hematopoietic Progenitor Cells: Synergistic Interaction of GM-CSF Plus G-CSF, Blood, Volume 74, Issue 1, 1989, Pages 110-114
Regarding claims 1, and 4-6, McNiece teaches the in vitro treatment of bone marrow samples with G-CSF, resulting in the formation of CD33+/CD34+ colony forming cells (McNiece, Abstract).
Scadden
Claim 1 and 7-9, 24, 36, and 48-49 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
Scadden (US20200268850A1) (Provided in IDS of 5/29/2024)
In view of Naeim (Faramarz Naeim, Chapter 2 - Principles of Immunophenotyping, Hematopathology, Academic Press, 2008, Pages 27-55)
As evidenced by Ibrahim (Ibrahim SA, Khan YS. Histology, Extracellular Vesicles. [Updated 2023 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan)
Regarding claim 1 and 7-9, Scadden teaches A method of mobilizing hematopoietic stem cells and/or progenitor cells in a subject, comprising administering to the subject a combination of a CXCR2 agonist and a CXCR4 antagonist, in amounts effective to mobilize hematopoietic stem cells and/or progenitor cells into the subject's peripheral blood. (Scadden, Claim 1). Scadden teaches that this method may further comprise the administration of G-CSF to the subject. (Scadden, Claim 5). Scadden then teaches that the mobilized circulating peripheral blood stem cells may then be transplanted from the donor to a subject in need thereof. (Scadden, claim 8). Scadden further teaches that in addition to these peripheral blood cells, the methods described herein contemplate any stem cell which would be useful for transplantation, including, but not limited to, peripheral blood stem cells, bone marrow stem cells, umbilical cord stem cells, genetically modified stem cells, etc. (Scadden [0151]).
In other words, Scadden teaches the administration of G-CSF to a subject and harvesting stem cells, including bone marrow and umbilical cord stem cells, from the subject.
However, Scadden does not specify that any of these cells exposed to G-CSF/ engineered cells are necessarily CD33+.
CD33 is expressed by myeloid stem cells (CFU-GEMM, CFU-GM, CFU-G, and E-BFU), myeloblasts and monoblasts, monocytes/macrophages, granulocyte precursors (with decreasing expression with maturation), and mast cells (Naeim).
Scadden in FIGS. 5B and 5C illustrates the results of bone marrow analysis showing contribution to committed myeloid progenitors (common myeloid progenitor (CMP), granulocyte-monocyte progenitor (GMP), and megakaryocyte-erythrocyte progenitors (MEP) and committed lymphoid progenitors (CLP) (i.e., types of myeloid stem cell/progenitor cells and monocyte cells). Scadden also teaches that at least some of the peripheral blood cells that they were transplanting were myeloid cells, i.e. CD33+ cells. (Scadden [0123], Fig 6K myeloid cells (Mac1 and Gr1)).
Thus, it is reasonable to assume that at least some of Scadden’s engineered cells expressed the CD33 transmembrane protein, including after being exposed to G-CSF while the cells were present in the subject, i.e. Scadden teaches CD33+ engineered cells.
Regarding claim 24, Scadden teaches the administration of G-CSF to a donor prior to harvesting progenitor cells from the peripheral blood of the donor (Scadden, claim 1, 5, 8, 10). Scadden also treatment of a subject via transplantation of their engineered stem cells (Scadden, Abstract, claim 8, claim 10). According to the specification, the term “engineered cell” refers to a cell modified by means of genetic engineering, or polarization with, for example, soluble factors and/or ligands, or isolated cells with characteristics differing from any naturally occurring cell (Specification [0088]). In effect, after administration of G-CSF to the donor, every cell in the donor’s body is an “engineered cell” according to the definition given in the specification.
Scadden teaches that their treatment method may use any stem cell which would be useful for transplantation, including, but not limited to, peripheral blood stem cells, bone marrow stem cells, umbilical cord stem cells, genetically modified stem cells, etc. (Scadden [0151]). Scadden also teaches that at least some of the peripheral blood cells that they were transplanting were myeloid cells, i.e. CD33+ cells. (Scadden [0123], Fig 6K myeloid cells (Mac1 and Gr1)).
Regarding a method of treatment of a neurological disorder comprising administering a therapeutically effective amount of the claimed engineered cell, at least some of Scadden’s engineered cells in the donor’s peripheral blood expressed the CD33 transmembrane protein. (Scadden [0123], Fig 6K myeloid cells (Mac1 and Gr1)). Scadden teaches the administration of this composition comprising CD33+ engineered cells to a subject in need thereof (Scadden, Abstract, claims 1, 5, 8, 10). Regarding the treatment of a neurological disease specifically, Scadden teaches that in some embodiments, the subject receiving transplanted donor cells is suffering from polyradiculoneuropathy, which is a neurological disorder (Scadden [0024]).
Regarding claim 36, Scadden teaches the treatment of a neurological disorder with the claimed engineered cell, but does not specify that the treatment necessarily improves the regeneration of a nerve cell in a subject.
However, Scadden does teach the administration of an effective amount of a composition comprising an engineered CD33+ cell in order to treat a neurological disease (see rejection of claim 24). C
As discussed in MPEP § 2112, citing In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594), the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case, there is reason to believe that Scadden’s method of treatment of a neurological disease results in at least some regeneration of a nerve cell in a subject, since Scadden’s treatment method is identical to the claimed treatment method, so any result of that treatment would also necessarily be taught/expected.
Regarding claim 48 and 49, Scadden teaches the administration of a composition comprising CD33+ (Myeloid) engineered cells, along with other peripheral blood cells, to treat a neurological disorder in a subject. (Scadden, Abstract, Claims 1, 5, 8, 10, [0024]).). Scadden does not specify that extracellular vesicles (EVs) are also within their composition. However, if Scadden’s composition reasonably comprised any EVs derived from the CD33+ engineered cell, that would be a “therapeutic amount” of an EV derived from a CD33+ engineered cell, and Scadden would teach the claimed composition of claim 48 and the method of claim 49.
So, if one of the engineered CD33+ (myeloid) cells in Scadden’s composition expresses EV, it is reasonable to expect that at least some EVs would be present in the composition Scadden administers in their treatment method. According to Ibrahim, Extracellular vesicles (EVs) are a cluster of nano-sized vesicles of different sizes, cargo, and surface markers that are secreted into the extracellular environment through a variety of mechanisms. They are secreted by all forms of living cells and play essential roles in different physiological functions and pathological processes. In humans, these EVs have been reported to be secreted by nearly all types of cells in our physique, including but not limited to immune cells, endothelial cells, red blood cells, erythrocytes, liver cells, and epithelial cells. (Ibrahim, Introduction).
As discussed in MPEP § 2112, citing In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594), the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case, there is reason to believe that Scadden’s composition comprising engineered CD33+ (myeloid) cells further comprised at least some vesicles derived from those engineered cells, since virtually every living cell excretes extracellular vesicles. So, Scadden’s treatment of a neurological disorder with their composition comprising engineered CD33+ myeloid cells also reasonably comprised EVs derived from the engineered cells as well.
Conclusion
Claims 1-16, 24, 36, 48, and 49 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THOMAS RUSSE AMICK whose telephone number is (571)272-5474. The examiner can normally be reached 7:30-5 M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/THOMAS R. AMICK/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
Prosecution Insights