DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of Group I (claims 1-13) with species (factor present in an umbilical cord blood derived macrophage cell population culture medium): apolipoprotein E (APOE), #45 in Table 1, page 44 in the reply filed on February 17, 2026 is acknowledged. The examination of factor species has been extended to include prostaglandin reductase 1 (PTGR1), #251 in Table 1, page 45.
3. Claims 1-20 are pending.
Claims 2-20, drawn to non-elected inventions are withdrawn from examination.
Claim 20 has been amended.
Claims 1-13 are examined on the merits with elected species, APOE and PTGR1.
Claim Objections
4. Claim 1 is objected to because of the following informality: the acronym, OPCs on line 4 is equivalent to oligodendrocyte precursor cells. However, the full meaning of the said acronym cited is in singular form, reading on one oligodendrocyte precursor cell as noted in claim 12, line 2.
Correction is required.
Claim Rejections - 35 USC § 112
5. 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.
6. Claims 1-13 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.
a. Claims 1 and 2 recite “[a] composition comprising at least one factor present in an umbilical cord blood derived macrophage cell population culture medium or a biologically active variant(s), derivative(s) or fragment(s) thereof,” on lines 2 and 3 of claim 1 and lines 3 and 4 of claim 2. It is not clear what version or how different the factor(s) should be from the known protein recited in claim 5, nor what part of the factor(s) are within the composition. Accordingly, the metes and bounds cannot be determined.
Claim Rejections - 35 USC § 102
7. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
8. Claim(s) 1, 2 and 4-13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kurtzberg et al., US 2019/0343882 A1 (published November 14, 2019/ IDS reference B1 submitted September 1, 2023). Kurtzberg discloses “…compositions including DUOC-01 cell product, derived from banked human umbilical cord blood (CB) mononuclear cells with a pharmaceutically acceptable carrier, see abstract; page 1, sections 0002, 0007 and 0011; page 5, section 0054 and 0055; and claims spanning pages 18 and 19. The DUOC-01 cells express an array of transcripts including [#45 within Table 1 on page apolipoprotein E] APOE, “APOC1 and COLEC112: lipid uptake receptors LRP5, LRP11 and LRP12; and lipid degrading LPL.”, as well as “(PTGDS, HPGDS, PTGES, PTGFRN, [#251 within Table 1 on page 45, prostaglandin reductase 1] PTGR1 and PTGR2)”, see page 15, section 0122. These transcripts are one and the same as factors.
The motile, phagocytic cells in DUOC-01 express CD45, CD11 b, CD14, CD16, CD206, ionized calcium binding adaptor molecule 1 (Iba1), HLA-DR, and iNOS, secrete IL-10 and IL-6”, see page 1, sections 0005, 0007; page 2, section 0013; page 4, section 0044; and claims on page 1.
The disclosed composition can be administered intrathecally, intrathecally (e.g., an administration into the spinal canal, or into the subarachnoid space, or into space under the arachnoid membrane of the brain), see page 1, section 0005; page 5, section 0050.
Once administered the disclosed composition is able to promote myelination of a neuron in presence of a primary oligodendrocyte precursor cell (OPCs) and treats a demyelination condition, see abstract; page 1, sections 0005, 0007, 0011; page 4, sections 0040, 0042; and claims spanning pages 18 and 19. Demyelinating conditions include is multiple sclerosis, leukodystrophies, spinal cord injury, peripheral nerve disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), or Alzheimer's disease, see page 1, sections 0009, 0010; page 2, section 0015; and page 4, sections 0042, 0043. It also natural flows that with the administration of the disclosed composition, myelination of a neuron in the presence of a primary oligodendrocyte precursor cell (OPC), a demyelination condition is reduce, reversed, treated and can drive the differentiation of an OPC to mature myelin basic protein expressing oligodendrocytes.
“[D]ata suggest that DUOC-01 cells express and secrete factors known to promote remyelination by several mechanisms and enhance oligodendrocyte precursor proliferation and differentiation.”, see last sentence in 2nd column on page 10. The proliferated and differentiated OPCs were within in vitro assays.
9. Claim(s) 1, 2 and 4-13 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kurtzberg et al., US 2021/0275583 A1 (effective filing date May 21, 2021). Kurtzberg discloses “…compositions including DUOC-01 cell product, derived from banked human umbilical cord blood (CB) mononuclear cells with a pharmaceutically acceptable carrier, see abstract; page 1, sections 0002, 0007 and 0011; page 5, section 0051; and claims spanning pages 21 and 22. The DUOC-01 cells express an array of transcripts including [#45 within Table 1 on page apolipoprotein E] APOE, “APOC1 and COLEC112: lipid uptake receptors LRP5, LRP11 and LRP12; and lipid degrading LPL.”, as well as “(PTGDS, HPGDS, PTGES, PTGFRN, [#251 within Table 1 on page 45, prostaglandin reductase 1] PTGR1 and PTGR2)”, see section 0148 bridging pages 16 and 17. These transcripts are one and the same as factors.
The motile, phagocytic cells in DUOC-01 express CD45, CD11 b, CD14, CD16, CD206, ionized calcium binding adaptor molecule 1 (Iba1), HLA-DR, and iNOS, secrete IL-10 and IL-6”, see page 1, sections 0005, 0008; page 2, sections 0013, 0016, 0018; page 5, section 0053; page 6, section 0069; page 7, section 0080; and claims on page 21.
The disclosed composition can be administered intrathecally, intrathecally (e.g., an administration into the spinal canal, or into the subarachnoid space, or into space under the arachnoid membrane of the brain), see page 1, section 0005; page 5, section 0059; and section 0061 spanning pages 5 and 6; page 6, section 0073; page 17, section 0152; and claims on page 21.
Once administered the disclosed composition is able to promote myelination of a neuron in presence of a primary oligodendrocyte precursor cell (OPCs), drive the differentiation of the OPC to mature myelin basic protein expressing oligodendrocytes and treats a demyelination condition, see abstract; page 1, sections 0005, 0007, 0011; sections 0049-0051 spanning pages 4 and 5; and claims spanning pages 21 and 22. Demyelinating conditions include is multiple sclerosis, leukodystrophies, spinal cord injury, peripheral nerve disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), or Alzheimer's disease, see page 1, sections 0009, 0010; page 2, section 0015; page 5, sections 0051, 0052, 0043; page 6, sections 0068, 0071, 0085; page 13, section 0138; and claims spanning pages 21 and 22. It also natural flows that with the administration of the disclosed composition, myelination of a neuron in the presence of a primary oligodendrocyte precursor cell (OPC), a demyelination condition is reduce, reversed, treated and can drive the differentiation of an OPC to mature myelin basic protein expressing oligodendrocytes.
“[D]ata suggest that DUOC-01 cells express and secrete factors known to promote remyelination by several mechanisms and enhance oligodendrocyte precursor proliferation and differentiation.”, see last sentence in 1st column on page 12. The proliferated and differentiated OPCs were within in vitro assays.
10. Claim(s) 1, 2, 4 and 6-13 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kurtzberg et al., US 11,278,575 B2 (filed July 12, 2019). Kurtzberg discloses compositions including DUOC-01 cell product and an anti-inflammatory agent in a pharmaceutically acceptable carrier for treatment of treating demyelinating conditions, see abstract; and column 2, lines 48-53. Demyelinating conditions include multiple sclerosis, leukodystrophies, spinal cord injury, peripheral nerve damage, Parkinson's disease, amyotrophic lateral sclerosis (ALS), or Alzheimer's disease, see paragraph bridging pages columns (cols.) 2 and 3; column (col.) 5, lines 1-21.
“The inventors have developed DUOC-01, a cell therapy product composed of cells with characteristics of macrophages and microglia that is intended for use in the treatment of demyelinating CNS diseases… The motile, phagocytic cells in DUOC-01 express CD45, CD11b, CD14, CD16, CD206, ionized calcium binding adaptor molecule 1 (Iba1), HLA-DR, and iNOS, secrete IL-10 and IL-6, and upregulate secretion of anti-inflammatory cytokines both constitutively and in response to TNF-α and IFN-γ…DUOC-01 cells derived from genetically normal umbilical cord blood donors also secrete a battery of lysosomal hydrolases that are missing in children with leukodystrophies. DUOC-01 [is] administered intrathecally…”, see col. 2, lines 3-18 and 54-59.
“DUOC-01 cell product of the disclosure expresses many other proteins that could participate more indirectly in promoting remyelination and in resolving cellular accumulation in the CC. Cytokine-activated microglia can stimulate the differentiation of oligodendrocytes from neural progenitor cells. While oligodendrocytes affect the remyelination of nerve fibers, other cell types are important for this repair process. Astrocytes provide trophic factors for oligodendrocytes and also for microglia. Microglia also provide trophic factors and remove myelin debris that inhibit remyelination by oligodendrocytes.”, see col. 6, lines 25-37. “[T]he DUOC-01 cell product includes cells that overexpress one or more of platelet-derived growth factor subunit A (PDGFA), KIT-ligand (KITLG, also known as stem cell factor [SCF]), insulin-like growth factor-1 (IGF1), triggering receptor expressed on myeloid cells 2 (TREM2), [see Applicant’s Table 1, #207, page 44] matrix metalloproteinase-9 (MMP9), and MMP12 transcripts. In certain embodiments, the expression of one or more of PDGFA, KITLG, IGF1, TREM2, MMP9, and MMP12 transcripts”, see col. 7, lines 5-18.
“Several of the proteins that are expressed by DUOC-01 cells are known to regulate the number or activity of oligodendrocyte progenitor cells (OPCs).”, see col. 6, lines 5-7.
Once administered the disclosed composition is able to promote myelination of a neuron in presence of a primary oligodendrocyte precursor cell (OPCs), drive the differentiation of the OPC to mature myelin basic protein expressing oligodendrocytes and treats a demyelination condition, see entire document.
The applied reference has a common assignee, applicant and inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Claim Rejections - 35 USC § 103
10. 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.
11. Claim(s) 1-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kurtzberg et al., US 2019/0343882 A1 (published November 14, 2019/ IDS reference B1 submitted September 1, 2023), and further in view of Pereira et al. (PLoS ONE 9(11): e113769, pages 18-31, published online November 25, 2014). Kurtzberg teaches “…compositions including DUOC-01 cell product, derived from banked human umbilical cord blood (CB) mononuclear cells with a pharmaceutically acceptable carrier, see abstract; page 1, sections 0002, 0007 and 0011; page 5, section 0054 and 0055; and claims spanning pages 18 and 19. The DUOC-01 cells express an array of transcripts including [#45 within Table 1 on page apolipoprotein E] APOE, “APOC1 and COLEC112: lipid uptake receptors LRP5, LRP11 and LRP12; and lipid degrading LPL.”, as well as “(PTGDS, HPGDS, PTGES, PTGFRN, [#251 within Table 1 on page 45, prostaglandin reductase 1] PTGR1 and PTGR2)”, see page 15, section 0122. These transcripts are one and the same as factors.
The motile, phagocytic cells in DUOC-01 express CD45, CD11 b, CD14, CD16, CD206, ionized calcium binding adaptor molecule 1 (Iba1), HLA-DR, and iNOS, secrete IL-10 and IL-6”, see page 1, sections 0005, 0007; page 2, section 0013; page 4, section 0044; and claims on page 1.
The taught composition can be administered intrathecally, intrathecally (e.g., an administration into the spinal canal, or into the subarachnoid space, or into space under the arachnoid membrane of the brain), see page 1, section 0005; page 5, section 0050.
Once administered the taught composition is able to promote myelination of a neuron in presence of a primary oligodendrocyte precursor cell (OPCs) and treats a demyelination condition, see abstract; page 1, sections 0005, 0007, 0011; page 4, sections 0040, 0042; and claims spanning pages 18 and 19. Demyelinating conditions include is multiple sclerosis, leukodystrophies, spinal cord injury, peripheral nerve disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), or Alzheimer's disease, see page 1, sections 0009, 0010; page 2, section 0015; and page 4, sections 0042, 0043. It also natural flows that with the administration of the disclosed composition, myelination of a neuron in the presence of a primary oligodendrocyte precursor cell (OPC), a demyelination condition is reduce, reversed, treated and can drive the differentiation of an OPC to mature myelin basic protein expressing oligodendrocytes.
“[D]ata suggest that DUOC-01 cells express and secrete factors known to promote remyelination by several mechanisms and enhance oligodendrocyte precursor proliferation and differentiation.”, see last sentence in 2nd column on page 10. The proliferated and differentiated OPCs were within in vitro assays.
Kurtzberg does not teach the disclosed composition comprises Remy-Macs.
However, Pereira teaches “…autologous [human umbilical cord plasma] hUCBP as a culture medium supplement in the cryopreservation process of isolated [human mesenchymal stem cells] hMSCs or of the [umbilical cord tissue] UCT, and in in vitro proliferation of hMSCs”, see page 4, last 11 lines of page. The culture media is enriched with growth factors produced by these hMSCs in expansion (Conditioned medium-CM) and “CM derived from hMSCs was demonstrated to contain factors that promote recruitment of macrophages and endothelial cells into the wound…[and] CM alone also has substantial effects on migration, proliferation, and overall wound”, see Abstract on page 1; and page 22.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of Kurtzberg and Periera to utilize products of infused umbilical cord blood MSCs because of the high preponderance “…that the CM where these cells [hMSCs] grow and expand in culture (CM) could be an appropriate therapeutic product rich in growth factors comparable to hMSCs local application” and “…the secretome of the unfused umbilical cord (UCB) MSCs can modulate the action of central nervous system (CNS) cells, which could be important in tissues with…low regenerative potential”, see page 2, last 6 lines of the page; page 5, lines 2-5; and both references in their entirety. And “the ex vivo expansion of hMSCs for therapeutic applications concerning cell therapies is necessary in almost every clinical case” and “in vitro expansion is necessary before performing clinical studies”, see page 18, last 5 lines; and sentence bridging pages 19 and 20.
One of ordinary skill in the art would have been motivated to do so
with a reasonable expectation of success by the teachings of both references, “evidence suggests that CM obtained from the in vitro culture and expansion of hMSCs and hematopoietic stem cells (CD34+ cells) or hUCBP are probably better therapeutic options compared to the in vivo transplantation of these stem cells. This is because the regenerating tissues can benefit from the local tissue response to the secreted molecules without the difficulties and complications associated to the engraftment of the allo-transplanted or xeno-transplanted cells”, see page 22.
Moreover, “hMSCS have been used in several clinal trials in children and adults over a wide range of pathologies and diseases”, see page 19, lines 3 and 4. hMSCs are one of the most promising types of stems cells for cell-based therapiets” because hMSCs are “one of the most promising types of stem cells for cell-based therapies… based on their differentiation capacity, hematopoietic support as well as their immunomodulatory and pro-regenerative properties”, as well as “have been tested in a large number of clinical trials for treatment of several pathologies like…”brain paralysis, SCI, cardiovascular diseases and myocardial infarction, type I diabetes, multiple sclerosis, Crohn's disease, bone fractures, graft-versus-host disease (GVHD) in bone marrow transplantation, osteoarthritis and rheumatoid arthritis “, see in particular, Pereira, page 2; page 3, 1st full paragraph (para.); and both references in their entirety.
12. Claim(s) 1-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kurtzberg et al., US 2021/0275583 A1 (effective filing date May 21, 2021), and further in view of Pereira et al. (PLoS ONE 9(11): e113769, pages 18-31, published online November 25, 2014). Kurtzberg teaches “…compositions including DUOC-01 cell product, derived from banked human umbilical cord blood (CB) mononuclear cells with a pharmaceutically acceptable carrier, see abstract; page 1, sections 0002, 0007 and 0011; page 5, section 0051; and claims spanning pages 21 and 22. The DUOC-01 cells express an array of transcripts including [#45 within Table 1 on page apolipoprotein E] APOE, “APOC1 and COLEC112: lipid uptake receptors LRP5, LRP11 and LRP12; and lipid degrading LPL.”, as well as “(PTGDS, HPGDS, PTGES, PTGFRN, [#251 within Table 1 on page 45, prostaglandin reductase 1] PTGR1 and PTGR2)”, see section 0148 bridging pages 16 and 17. These transcripts are one and the same as factors.
The motile, phagocytic cells in DUOC-01 express CD45, CD11 b, CD14, CD16, CD206, ionized calcium binding adaptor molecule 1 (Iba1), HLA-DR, and iNOS, secrete IL-10 and IL-6”, see page 1, sections 0005, 0008; page 2, sections 0013, 0016, 0018; page 5, section 0053; page 6, section 0069; page 7, section 0080; and claims on page 21.
The taught composition can be administered intrathecally, intrathecally (e.g., an administration into the spinal canal, or into the subarachnoid space, or into space under the arachnoid membrane of the brain), see page 1, section 0005; page 5, section 0059; and section 0061 spanning pages 5 and 6; page 6, section 0073; page 17, section 0152; and claims on page 21.
Once administered the taught composition is able to promote myelination of a neuron in presence of a primary oligodendrocyte precursor cell (OPCs), drive the differentiation of the OPC to mature myelin basic protein expressing oligodendrocytes and treats a demyelination condition, see abstract; page 1, sections 0005, 0007, 0011; sections 0049-0051 spanning pages 4 and 5; and claims spanning pages 21 and 22. Demyelinating conditions include is multiple sclerosis, leukodystrophies, spinal cord injury, peripheral nerve disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), or Alzheimer's disease, see page 1, sections 0009, 0010; page 2, section 0015; page 5, sections 0051, 0052, 0043; page 6, sections 0068, 0071, 0085; page 13, section 0138; and claims spanning pages 21 and 22. It also natural flows that with the administration of the disclosed composition, myelination of a neuron in the presence of a primary oligodendrocyte precursor cell (OPC), a demyelination condition is reduce, reversed, treated and can drive the differentiation of an OPC to mature myelin basic protein expressing oligodendrocytes.
“[D]ata suggest that DUOC-01 cells express and secrete factors known to promote remyelination by several mechanisms and enhance oligodendrocyte precursor proliferation and differentiation.”, see last sentence in 1st column on page 12. The proliferated and differentiated OPCs were within in vitro assays.
Kurtzberg does not teach the disclosed composition comprises Remy-Macs.
However, Pereira teaches “…autologous [human umbilical cord plasma] hUCBP as a culture medium supplement in the cryopreservation process of isolated [human mesenchymal stem cells] hMSCs or of the [umbilical cord tissue] UCT, and in in vitro proliferation of hMSCs”, see page 4, last 11 lines of page. The culture media is enriched with growth factors produced by these hMSCs in expansion (Conditioned medium-CM) and “CM derived from hMSCs was demonstrated to contain factors that promote recruitment of macrophages and endothelial cells into the wound…[and] CM alone also has substantial effects on migration, proliferation, and overall wound”, see Abstract on page 1; and page 22.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of Kurtzberg and Periera to utilize products of infused umbilical cord blood MSCs because of the high preponderance “…that the CM where these cells [hMSCs] grow and expand in culture (CM) could be an appropriate therapeutic product rich in growth factors comparable to hMSCs local application” and “…the secretome of the unfused umbilical cord (UCB) MSCs can modulate the action of central nervous system (CNS) cells, which could be important in tissues with…low regenerative potential”, see page 2, last 6 lines of the page; page 5, lines 2-5; and both references in their entirety. And “the ex vivo expansion of hMSCs for therapeutic applications concerning cell therapies is necessary in almost every clinical case” and “in vitro expansion is necessary before performing clinical studies”, see page 18, last 5 lines; and sentence bridging pages 19 and 20.
One of ordinary skill in the art would have been motivated to do so
with a reasonable expectation of success by the teachings of both references, “evidence suggests that CM obtained from the in vitro culture and expansion of hMSCs and hematopoietic stem cells (CD34+ cells) or hUCBP are probably better therapeutic options compared to the in vivo transplantation of these stem cells. This is because the regenerating tissues can benefit from the local tissue response to the secreted molecules without the difficulties and complications associated to the engraftment of the allo-transplanted or xeno-transplanted cells”, see page 22.
Moreover, “hMSCS have been used in several clinal trials in children and adults over a wide range of pathologies and diseases”, see page 19, lines 3 and 4. hMSCs are one of the most promising types of stems cells for cell-based therapiets” because hMSCs are “one of the most promising types of stem cells for cell-based therapies… based on their differentiation capacity, hematopoietic support as well as their immunomodulatory and pro-regenerative properties”, as well as “have been tested in a large number of clinical trials for treatment of several pathologies like…”brain paralysis, SCI, cardiovascular diseases and myocardial infarction, type I diabetes, multiple sclerosis, Crohn's disease, bone fractures, graft-versus-host disease (GVHD) in bone marrow transplantation, osteoarthritis and rheumatoid arthritis “, see in particular, Pereira, page 2; page 3, 1st full paragraph (para.); and both references in their entirety.
13. Claims 1-13 is/are provisionally rejected under 35 U.S.C. 103 as being obvious over copending Application No. 11,278,575 (filed July 12, 2019) which has a common assignee, inventor and/or applicant with the instant application and further in view of Kurtzberg et al., US 2019/0343882 A1 (published November 14, 2019/ IDS reference B1 submitted September 1, 2023) and Pereira et al. (PLoS ONE 9(11): e113769, pages 18-31, published online November 25, 2014). The copending application would constitute prior art under 35 U.S.C.102(a)(2) if published or patented. This provisional rejection under 35 U.S.C. 103 is based upon a presumption of future publication or patenting of the copending application.
The Kurtzberg patent teaches compositions including DUOC-01 cell product and an anti-inflammatory agent in a pharmaceutically acceptable carrier for treatment of treating demyelinating conditions, see abstract; and column 2, lines 48-53. Demyelinating conditions include multiple sclerosis, leukodystrophies, spinal cord injury, peripheral nerve damage, Parkinson's disease, amyotrophic lateral sclerosis (ALS), or Alzheimer's disease, see paragraph bridging pages columns (cols.) 2 and 3; and column (col.) 5, lines 1-21.
“The inventors have developed DUOC-01, a cell therapy product composed of cells with characteristics of macrophages and microglia that is intended for use in the treatment of demyelinating CNS diseases… The motile, phagocytic cells in DUOC-01 express CD45, CD11b, CD14, CD16, CD206, ionized calcium binding adaptor molecule 1 (Iba1), HLA-DR, and iNOS, secrete IL-10 and IL-6, and upregulate secretion of anti-inflammatory cytokines both constitutively and in response to TNF-α and IFN-γ…DUOC-01 cells derived from genetically normal umbilical cord blood donors also secrete a battery of lysosomal hydrolases that are missing in children with leukodystrophies. DUOC-01 [is] administered intrathecally…”, see col. 2, lines 3-18 and 54-59.
“DUOC-01 cell product of the disclosure expresses many other proteins that could participate more indirectly in promoting remyelination and in resolving cellular accumulation in the CC. Cytokine-activated microglia can stimulate the differentiation of oligodendrocytes from neural progenitor cells. While oligodendrocytes affect the remyelination of nerve fibers, other cell types are important for this repair process. Astrocytes provide trophic factors for oligodendrocytes and also for microglia. Microglia also provide trophic factors and remove myelin debris that inhibit remyelination by oligodendrocytes.”, see col. 6, lines 25-37. “[T]he DUOC-01 cell product includes cells that overexpress one or more of platelet-derived growth factor subunit A (PDGFA), KIT-ligand (KITLG, also known as stem cell factor [SCF]), insulin-like growth factor-1 (IGF1), triggering receptor expressed on myeloid cells 2 (TREM2), [see Applicant’s Table 1, #207, page 44] matrix metalloproteinase-9 (MMP9), and MMP12 transcripts. In certain embodiments, the expression of one or more of PDGFA, KITLG, IGF1, TREM2, MMP9, and MMP12 transcripts”, see col. 7, lines 5-18.
“Several of the proteins that are expressed by DUOC-01 cells are known to regulate the number or activity of oligodendrocyte progenitor cells (OPCs).”, see col. 6, lines 5-7.
Once administered the disclosed composition is able to promote myelination of a neuron in presence of a primary oligodendrocyte precursor cell (OPCs), drive the differentiation of the OPC to mature myelin basic protein expressing oligodendrocytes and treats a demyelination condition, see entire document.
The Kurtzberg patent does not teach the composition comprising Remy-Macs and the factors present in an umbilical cord blood derived macrophage cell population culture medium is apolipoprotein E (APOE), #45 in Table 1, page 44 and prostaglandin reductase 1 (PTGR1), #251 in Table 1, page 45.
However, the US Kurtzberg publication teaches compositions including DUOC-01 cell product, which express an array of transcripts including [#45 within Table 1 on page apolipoprotein E] APOE, “APOC1 and COLEC112: lipid uptake receptors LRP5, LRP11 and LRP12; and lipid degrading LPL.”, as well as “(PTGDS, HPGDS, PTGES, PTGFRN, [#251 within Table 1 on page 45, prostaglandin reductase 1] PTGR1 and PTGR2)”, see page 15, section 0122. These transcripts are one and the same as factors.
Furthermore, Pereira teaches “…autologous [human umbilical cord plasma] hUCBP as a culture medium supplement in the cryopreservation process of isolated [human mesenchymal stem cells] hMSCs or of the [umbilical cord tissue] UCT, and in in vitro proliferation of hMSCs”, see page 4, last 11 lines of page. The culture media is enriched with growth factors produced by these hMSCs in expansion (Conditioned medium-CM) and “CM derived from hMSCs was demonstrated to contain factors that promote recruitment of macrophages and endothelial cells into the wound…[and] CM alone also has substantial effects on migration, proliferation, and overall wound”, see Abstract on page 1; and page 22.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine teachings of both Kurtzberg documents to identify additional factors and Periera to utilize products of infused umbilical cord blood MSCs because of the high preponderance “…that the CM where these cells [hMSCs] grow and expand in culture (CM) could be an appropriate therapeutic product rich in growth factors comparable to hMSCs local application” and “…the secretome of the unfused umbilical cord (UCB) MSCs can modulate the action of central nervous system (CNS) cells, which could be important in tissues with…low regenerative potential”, see page 2, last 6 lines of the page; page 5, lines 2-5; and both references in their entirety. And “the ex vivo expansion of hMSCs for therapeutic applications concerning cell therapies is necessary in almost every clinical case” and “in vitro expansion is necessary before performing clinical studies”, see page 18, last 5 lines; and sentence bridging pages 19 and 20.
One of ordinary skill in the art would have been motivated to do so
with a reasonable expectation of success by the teachings of the US Pub Kurtzberg to identify factors that are therapeutic and all references, “evidence suggests that CM obtained from the in vitro culture and expansion of hMSCs and hematopoietic stem cells (CD34+ cells) or hUCBP are probably better therapeutic options compared to the in vivo transplantation of these stem cells. This is because the regenerating tissues can benefit from the local tissue response to the secreted molecules without the difficulties and complications associated to the engraftment of the allo-transplanted or xeno-transplanted cells”, see all references, and in particular the US Pub. Kurtzberg; and Pereira page 22.
Moreover, “hMSCS have been used in several clinal trials in children and adults over a wide range of pathologies and diseases”, see page 19, lines 3 and 4. hMSCs are one of the most promising types of stems cells for cell-based therapiets” because hMSCs are “one of the most promising types of stem cells for cell-based therapies… based on their differentiation capacity, hematopoietic support as well as their immunomodulatory and pro-regenerative properties”, as well as “have been tested in a large number of clinical trials for treatment of several pathologies like…”brain paralysis, SCI, cardiovascular diseases and myocardial infarction, type I diabetes, multiple sclerosis, Crohn's disease, bone fractures, graft-versus-host disease (GVHD) in bone marrow transplantation, osteoarthritis and rheumatoid arthritis “, see in particular, Pereira, page 2; page 3, 1st full paragraph (para.); and all references in their entirety.
This provisional rejection might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the copending application was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the copending application and the claimed invention either were owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Double Patenting
14. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
15. Claims 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-8, 10, 18 and 22 of copending Application No. 16/477,167 (filed July 10, 2019). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims read a composition comprising a DUOC-01 cell product expressing macrophage and/or microglia markers and secrete IL-6 and IL10 with at least one excipient. The said composition is able to treat demyelinating conditions and administered intrathecally.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
16. Claims 1-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8, 13-15, 18-20 of copending Application No. 17/328,749 (May 24, 2021). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims read a composition comprising a DUOC-01 cell product expressing macrophage and/or microglia markers and secrete IL-6 and IL10 with at least one excipient. The said composition is able to treat demyelinating conditions and administered intrathecally.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
17. Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-11, 14 and 15 of U.S. Patent No. 11,278,575 B2 (issued March 22, 2022). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims read a composition comprising a DUOC-01 cell product expressing macrophage and/or microglia markers and secrete IL-6 and IL10 with at least one excipient. The said composition is able to treat demyelinating conditions and administered intrathecally.
Conclusion
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
March 4, 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643