+-+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 .
Applicant’s amendment filed on 12/23/2025 has been entered.
Claims 29-42, 44-46 and 48 are pending in the present application.
Applicant elected previously without traverse the Invention of Group II.
Applicant also elected previously the following species: (i) Neutrophilic promyelocytes; and (ii) Granulocyte colony-stimulating factor (G-CSF).
Claims 29-41 were withdrawn previously from further consideration because they are directed to a non-elected invention.
Accordingly, amended claims 42, 44-46 and 48 are examined on the merits herein with the above elected species.
Claim Rejections - 35 USC § 102/103
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.
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.
Amended claims 42 and 45-46 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by or under 35 U.S.C. 103 as being unpatentable over Fong et al (WO 2006/047569). This is a modified rejection necessitated by Applicant’s amendment.
Amended claims 42 and 45 are directed to a pharmaceutical composition comprising: a. a granulocyte precursor cell derived ex vivo from a haematopoietic cell, wherein the granulocyte precursor cell is selected from a neutrophilic promyelocyte (elected species), a neutrophilic myelocyte, a neutrophilic metamyelocyte, a neutrophilic band cell, or a combination thereof; and b. a carrier; while claims 46 is drawn to a kit comprising: a. a granulocyte precursor cell derived ex vivo from a haematopoietic cell, wherein the granulocyte precursor cell is selected from a neutrophilic promyelocyte (elected species), a neutrophilic myelocyte, a neutrophilic metamyelocyte, a neutrophilic band cell, or a combination thereof; and b. instructions for use of the same in medicine.
It is noted that the scope of canceled claims 43 and 47 is not the same as that of currently amended independent claims 42 and 46, particularly with the deletion of the terms “a common myeloid progenitor cell” and “a myeloblast” in currently amended independent claims 42 and 46.
Fong et al already disclosed at least a therapeutic composition comprising an ex vivo cultured expanded population of myeloid progenitor cells and a pharmaceutically acceptable medium, wherein the starting/initial cell population includes hematopoietic stem cells that are derived from an allogeneic donor or from a plurality of allogeneic donors (Abstract; Summary; particularly paragraphs [0013], [0015]-[0016], and [00112]-[00114]). Fong et al also taught that expanded myeloid progenitor cells generally comprise common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP) (paragraph [0022]), and that the myeloid progenitor cells were generated and expanded by contacting hematopoietic stem cells with a culture medium comprising a cytokine and growth factor mixture that includes G-CSF and GM-CSF (paragraph [0018]). Fong et al disclosed that G-CSF acts to induce the bone marrow to produce granulocytes, and promote the survival, proliferation, differentiation and function of neutrophil granulocyte progenitor cells and mature neutrophils (paragraph [00120]), and stated “In instances where more mature cells of the myeloid lineage are desired to enhance immediate protection against neutropenia and/or thrombocytopenia, the cytokines G-CSF or GM-CSF is added to the foregoing cytokine mixture. This may be done after an initial period of growth in media lacking G-CSF or GM-CSF to permit expansion of more primitive myeloid progenitor cells prior to promoting differentiation into the progenitor cells that are further along in the myeloid lineage” (paragraph [00131]). Fong et al further disclosed kits containing the cytokine and growth factor mixture, initial cells for expansion, media and other necessary components for carrying out the ex vivo expansion methods; as well as kits to use the cell population, expanded or unexpanded, for therapeutic application; and the kits further include labels, buffers and instructions for methods of using the kits (paragraph [0031]). Fong et al stated specifically “Other embodiments of the compositions described herein are kits comprising the expanded and/or isolated myeloid progenitor cells, cytokines and growth factors (e.g., G-CSF, GM-CSF, TPO) and/or adjunctive therapeutic compounds. A label typically accompanies the kit, and includes any writing or recorded material, which may be electronic or computer readable form (e.g., disk, optical disc, memory chip, or tape) providing instructions or other information for use of the kit contents” (paragraph [00188]).
With respect to the elected species of “a neutrophilic promyelocyte”, since the ex vivo expanded myeloid progenitor cells of Fong et al already comprise common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP) in a culture medium comprising G-CSF which is known to promote differentiation of more primitive myeloid progenitor cells into progenitor cells that are further along in the myeloid lineage, and the expanded myeloid progenitor cells are also derived from hematopoietic stem cells; such a population of expanded myeloid progenitor cells of Fong et al also comprises a neutrophilic promyelocyte (derived from GMP which in turn is derived from CMP). Please, also note that where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. See In re Ludtke. Whether the rejection is based on "inherency" under 35 USC 102, or "prima facie obviousness" under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, Bolton, and Shaw, 195 USPQ 430, 433 (CCPA 1977) citing In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972).
Accordingly, the teachings of Fong et al meet every limitation of the instant claims. Therefore, the reference anticipates the instant claims.
Alternatively; although Fong et al do not explicitly teach or mention a neutrophilic promyelocyte as a granulocyte precursor, it would have been obvious for an ordinary skill in the art to recognize that since the ex vivo expanded myeloid progenitor cells of Fong et al already comprise common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP) in a culture medium comprising G-CSF which is known to promote differentiation of more primitive myeloid progenitor cells into progenitor cells that are further along in the myeloid lineage, and the expanded myeloid progenitor cells are also derived from hematopoietic stem cells; such a population of expanded myeloid progenitor cells of Fong et al also comprises a neutrophilic promyelocyte (derived from GMP which in turn is derived from CMP).
Please, also note that where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. See In re Ludtke. Whether the rejection is based on "inherency" under 35 USC 102, or "prima facie obviousness" under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, Bolton, and Shaw, 195 USPQ 430, 433 (CCPA 1977) citing In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972).
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments related to the above 102/103 rejection in the Amendment dated 12/23/2025 (pages 6-7) have been fully considered, but they are respectfully not found persuasive for the reasons discussed below.
Applicant argued basically that at most Fong discloses that expanded myeloid progenitor cells generally comprise CMP, GMP, and MEP, and any further inference to the cells disclosed by Fong is conclusory and unsupported. Applicant also argued that an ordinary skill in the art would understand that CMP, GMP and MEP are upstream stages in the myeloid lineage, not yet committed to a specific mature cell type, and that a complex set of factors, beyond the mere presence of G-CSF and including the timing and sequence of signaling events, will dictate the further development of such cells. Applicant further argued that an ordinary skill in the art would know that MEP do not develop into any of the cell types claimed and GMP diversify into myriad cell types; and there is no mention in Fong of the claimed neutrophilic promyelocyte, a neutrophilic myelocyte, a neutrophilic metamyelocyte, and neutrophilic band cell. Additionally, Applicant argued that merely stating that more primitive myeloid progenitor cells can differentiate is insufficient; and Fong also fails to disclose how cells downstream of CMP, GMP and MEP can be obtained and it does not provide any clear evidence that such downstream cells, including more differentiated granulocyte precursors, have in fact been generated. According, Fong does not teach or suggest each and every limitation of the amended claims.
First, the teachings of Fong are not necessarily limited to an ex vivo cultured expanded population of myeloid progenitor cells comprising only of common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP), particularly an ex vivo cultured expanded population of myeloid progenitor cells in a culture medium comprising G-CSF. Fong stated clearly “The expanded cells described herein comprise committed myeloid progenitor cells (MP) generated by contacting an initial population of stem cells and progenitors with a defined cytokine and growth factor mixture permissive for the development of the committed myeloid progenitor cells” (paragraph [0055]); ““Committed myeloid progenitor cells” or “myeloid progenitor cell” refers to a multipotent or unipotent progenitor cell, capable of ultimately developing into any of the terminally differentiated cells of the myeloid lineage, but which do not typically differentiate into cells of the lymphoid lineage. Hence, “myeloid progenitor cell” refers to any progenitor cell in the myeloid lineage. Committed progenitor cells of the myeloid lineage include oligopotent CMP, GMP, and MEP as defined herein, but also encompass unipotent erythroid progenitor, megakaryocyte progenitor, granulocyte progenitor, and macrophage progenitor cells.” (paragraph [0063]); “Accordingly, cytokines for expansion conditions are generally selected from IL-1 (i.e., IL-1β), IL-3, IL-6, IL-11, G-CSF, GM-CSF, and analogs thereof” (first sentence of paragraph [00114]); “G-CSF or granulocyte-colony stimulating factor acts to induce the bone marrow to produce granulocytes, and promote the survival, proliferation, differentiation and function of neutrophil granulocyte progenitor cells and mature neutrophils” (first sentence of paragraph [00120]); and “In instances, where more mature cells of the myeloid lineage are desired to enhance immediate protection against neutropenia and/or thrombocytopenia, the cytokines G-CSF or GM-CSF is added to the foregoing cytokine mixtures. This may be done after an initial period of growth media lacking G-CSF or GM-CSF to permit expansion of more primitive myeloid progenitor cells prior to promoting differentiation into the progenitor cells that are further along in the myeloid lineage” (paragraph [00131]). Moreover, in an exemplification even in the absence of G-CSF or GM-CSF in a culture medium, in addition of the various well-defined myeloid progenitors, the culture already contains mature, and terminally differentiated megakaryocytes, albeit in a small amount; let alone myeloid progenitors further along in the myeloid lineage such as neutrophilic promyelocytes and especially with G-CSF in the culture medium (paragraph [00214]).
Second, as set forth in the above 102/103 rejection since the ex vivo expanded myeloid progenitor cells of Fong et al already comprise common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP) in a culture medium comprising G-CSF which is known to promote differentiation of more primitive myeloid progenitor cells into progenitor cells that are further along in the myeloid lineage, and the expanded myeloid progenitor cells are also derived from hematopoietic stem cells; such a population of expanded myeloid progenitor cells of Fong et al also comprises a neutrophilic promyelocyte (derived from GMP which in turn is derived from CMP). Alternatively, although Fong et al do not explicitly teach or mention a neutrophilic promyelocyte as a granulocyte precursor, it would have been obvious for an ordinary skill in the art to recognize that since the ex vivo expanded myeloid progenitor cells of Fong et al already comprise common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP) in a culture medium comprising G-CSF which is known to promote differentiation of more primitive myeloid progenitor cells into progenitor cells that are further along in the myeloid lineage, and the expanded myeloid progenitor cells are also derived from hematopoietic stem cells; such a population of expanded myeloid progenitor cells of Fong et al also comprises a neutrophilic promyelocyte (derived from GMP which in turn is derived from CMP).
Please, also note that where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. See In re Ludtke. Whether the rejection is based on "inherency" under 35 USC 102, or "prima facie obviousness" under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, Bolton, and Shaw, 195 USPQ 430, 433 (CCPA 1977) citing In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972).
To further support the Examiner’s position, Saito et al (Int. J. Hematol. 88:64-72, 2008; IDS) already taught that when highly purified human CD34+ cells were culture for 7 days with G-CSF alone, the generated cells predominantly expressed a granulocyte marker, CD15 (neutrophil progenitors), and then differentiated into neutrophils after 14 days of culture (Abstract).
Third, the differentiation of MEP into cell types other those being claimed is irrelevant. Moreover, please note that the instant claims encompass a pharmaceutical composition or a kit comprising a granulocyte precursor cell derived from a haematopoietic cell, as long as the granulocyte precursor cell is a neutrophilic promyelocyte (elected species). Thus, the composition or a kit may contain multiple cell types in addition to a neutrophilic promyelocyte.
Claim Rejections - 35 USC § 103
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.
Amended claims 42, 44, 46 and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Fong et al (WO 2006/047569) in view of Cui et al (US 2008/0089875; IDS). This is a modified rejection necessitated by Applicant’s amendment.
Fong et al already disclosed at least a therapeutic composition comprising an ex vivo cultured expanded population of myeloid progenitor cells and a pharmaceutically acceptable medium, wherein the starting/initial cell population includes hematopoietic stem cells that are derived from an allogeneic donor or from a plurality of allogeneic donors (Abstract; Summary; particularly paragraphs [0013], [0015]-[0016], and [00112]-[00114]). Fong et al also taught that expanded myeloid progenitor cells generally comprise common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP) (paragraph [0022]), and that the myeloid progenitor cells were generated and expanded by contacting hematopoietic stem cells with a culture medium comprising a cytokine and growth factor mixture that includes G-CSF and GM-CSF (paragraph [0018]). Fong et al disclosed that G-CSF acts to induce the bone marrow to produce granulocytes, and promote the survival, proliferation, differentiation and function of neutrophil granulocyte progenitor cells and mature neutrophils (paragraph [00120]), and stated “In instances where more mature cells of the myeloid lineage are desired to enhance immediate protection against neutropenia and/or thrombocytopenia, the cytokines G-CSF or GM-CSF is added to the foregoing cytokine mixture. This may be done after an initial period of growth in media lacking G-CSF or GM-CSF to permit expansion of more primitive myeloid progenitor cells prior to promoting differentiation into the progenitor cells that are further along in the myeloid lineage” (paragraph [00131]). Fong et al further disclosed kits containing the cytokine and growth factor mixture, initial cells for expansion, media and other necessary components for carrying out the ex vivo expansion methods; as well as kits to use the cell population, expanded or unexpanded, for therapeutic application; and the kits further include labels, buffers and instructions for methods of using the kits (paragraph [0031]). Fong et al stated specifically “Other embodiments of the compositions described herein are kits comprising the expanded and/or isolated myeloid progenitor cells, cytokines and growth factors (e.g., G-CSF, GM-CSF, TPO) and/or adjunctive therapeutic compounds. A label typically accompanies the kit, and includes any writing or recorded material, which may be electronic or computer readable form (e.g., disk, optical disc, memory chip, or tape) providing instructions or other information for use of the kit contents” (paragraph [00188]).
With respect to the elected species of “a neutrophilic promyelocyte”, although Fong et al do not explicitly teach or mention a neutrophilic promyelocyte as a granulocyte precursor, it would have been obvious for an ordinary skill in the art to recognize that since the ex vivo expanded myeloid progenitor cells of Fong et al already comprise common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP) in a culture medium comprising G-CSF which is known to promote differentiation of more primitive myeloid progenitor cells into progenitor cells that are further along in the myeloid lineage, and the expanded myeloid progenitor cells are also derived from hematopoietic stem cells; such a population of expanded myeloid progenitor cells of Fong et al also comprises a neutrophilic promyelocyte (derived from GMP which in turn is derived from CMP).
Please, also note that where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. See In re Ludtke. Whether the rejection is based on "inherency" under 35 USC 102, or "prima facie obviousness" under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, Bolton, and Shaw, 195 USPQ 430, 433 (CCPA 1977) citing In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972).
Fong et al also did not teach specifically that the hematopoietic stem cell is derived from a donor that produces granulocytes that kill at least 5% of cancer cells in a cancer killing assay.
Before the effective filing date of the present application (10/25/2017), Cui et al already taught a method of treating cancer using allogeneic white blood cells, particularly innate immune cells (e.g., granulocytes such as neutrophils, basophils and eosinophils), that are obtained from a healthy allogeneic donor and are screened for ability to kill cancer cells in vitro (Abstract; Summary of the Invention; particularly paragraphs [0005]-[0007], [0014], [0018]; and Examples 1-3). Cui et al stated “After sampling a group of volunteers using this unique blood test, it was found that healthy humans had a wide range of cancer-cell-killing activity (CKA; FIG. 1). On a 0% to 100% scale, WBCs from many healthy humans had significant levels of naturally-present activity ranging between 40% and 60%, with some as high as that of cancer-resistant mice at levels of 70% to 90%...Overall, healthy persons had a higher CKA than their age-matched counterparts whom had cancer. Intriguingly, individuals over the age of 50 also demonstrated an overall lower CKA than a younger comparison group” (paragraph [034]); “Separation of white blood cells into granulocyte and agranulocyte types indicated that the CKA was present in the granulocyte fraction (FIG. 2C)” (paragraph [0045]); and “Given that in vitro CKA for WBCs was attributed to the granulocyte fraction, the in vivo CKA of granulocytes is expected to be useful in the treatment of cancer” (paragraph [0046]).
Accordingly, it would have been obvious before the filing date of the present application for an ordinary skilled artisan to modify the teachings of Fong et al by also selecting/obtaining hematopoietic stem cells derived from a young healthy donor that produces granulocytes that kill at least 5% of cancer cells in a cancer killing assay to be a starting/initiating cell population for generating an ex vivo expanded population of myeloid progenitor cells, in light of the teachings of Cui et al as presented above.
An ordinary skilled artisan would have been motivated to carry out the above modification because Cui et al already taught successfully a method of treating cancer using allogeneic white blood cells, particularly innate immune cells (e.g., granulocytes such as neutrophils, basophils and eosinophils), that are obtained from a healthy allogeneic donor and are screened for ability to kill cancer cells in vitro; and established that the CKA (cancer-cell-killing activity) was present in the granulocyte fraction. The resulting modified pharmaceutical composition comprising the ex vivo expanded myeloid progenitor cells containing common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP) would also be useful as a source of granulocytes for cancer treatment. Moreover, please note that the primary Fong reference already taught that the starting/initial cell population includes hematopoietic stem cells that are derived from an allogeneic donor or from a plurality of allogeneic donors.
An ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Fong et al and Cui et al; coupled with a high level of skill for an ordinary skilled artisan in the relevant art.
The modified compositions resulting from the combined teachings of Fong et al and Cui et al as set forth above are indistinguishable and encompassed by the presently claimed method.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments related to the above modified 103 rejection in the Amendment dated 12/23/2025 (pages 7-8) have been fully considered, but they are respectfully not found persuasive for the reasons discussed below.
Applicant argued that there is no mention in Fong of the claimed neutrophilic promyelocyte, a neutrophilic myelocyte, a neutrophilic metamyelocyte, and neutrophilic band cell; and merely stating that more primitive myeloid progenitor cells can differentiate is insufficient. Additionally, Applicant argued that Fong also fails to disclose how cells downstream of CMP, GMP and MEP can be obtained and it does not provide any clear evidence that such downstream cells, including more differentiated granulocyte precursors, have in fact been generated. Applicant further argued that Cui (US Patent No. 6893633) discloses the use of GM-CSF and G-CSF to boost white blood counts and/or to “facilitate the development of monocytes to dendritic cells” (col. 2, lines 38-39); and one skill in the art would know that dendritic cells are from a different lineage than the claimed neutrophilic promyelocyte, a neutrophilic myelocyte, a neutrophilic metamyelocyte, and neutrophilic band cell. Thus, one of ordinary skill in the art would not interpret Fong as modified by Cui as disclosing that it unavoidably teaches the property in question.
First, with respect to the deficiencies of the Fong reference please refer to the Examiner’s same responses to Applicant’s arguments related to the 102/103 rejection above.
Second, the above rejection was made under 35 U.S.C. 103 as being unpatentable over Fong et al (WO 2006/047569) in view of Cui et al (US 2008/0089875; IDS); and it does not rely on Cui (US Patent No. 6893633) as stated by Applicant. Moreover, US Patent No. 6893633 is issued to Hellstrand et al and not to Cui et al.
Third, Example 1 in US Patent No. 6893633 simply showed that 88% of isolated monocytes expressing CD86 after overnight incubation with GM-CSF, while the corresponding figure for isolated monocytes treated with GM-CSF+histamine was 97%. However, this is not in the same context of the ex vivo expanded myeloid progenitor cells of Fong et al already comprising common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP) in a culture medium comprising G-CSF which is known to promote differentiation of more primitive myeloid progenitor cells into progenitor cells that are further along in the myeloid lineage, particularly G-CSF or granulocyte-colony stimulating factor acts to induce the bone marrow to produce granulocytes, and promote the survival, proliferation, differentiation and function of neutrophil granulocyte progenitor cells and mature neutrophils . Moreover, the prior art in the form of Saito et al (Int. J. Hematol. 88:64-72, 2008; IDS) already taught that when highly purified human CD34+ cells were culture for 7 days with G-CSF alone, the generated cells predominantly expressed a granulocyte marker, CD15 (neutrophil progenitors), and then differentiated into neutrophils after 14 days of culture (Abstract).
Fourth, the Cui reference was cited to supplement the teachings of Fong et al on the limitation of “wherein the haematopoietic cell is derived from a donor that produces granulocytes that kill at least 5% of cancer cells in a cancer killing assay” recited in dependent claims 44 and 48. Please refer to the above modified 103 rejection for details, including the provided motivation for combing the cited references.
Fifth, please also note that standard under 35 U.S.C. 103 is a “reasonable” expectation of success.
Double Patenting
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.
Amended claims 42 and 44-45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,642,373.
Although the claims at issue are not identical, they are not patentably distinct from each other because a method of formulating a cancer-cell killing formulation comprising: selecting hematopoietic stem and/or precursor cells (e.g., comprising hematopoietic stem cells, common myeloid progenitor cells, myeloblasts, N. promyelocytes, N. myelocytes, N. metamyelocytes, N. bands, or combinations thereof; dependent claim 3) derived from a donor that produces granulocytes with the ability to kill cancer cells (e.g., the donor produces granulocytes which kill at least 5% of cancer cells in a cancer killing assay; dependent claim 15); and formulating the selected hematopoietic stem and/or precursors within a carrier (e.g., a pharmaceutically acceptable carrier, TNFα, GM-CSF, G-CSF, a growth hormone, or combinations thereof; dependent claim 8); thereby formulating the cancer-cell killing formulation; and a cancer-cell killing formulation produced by the same method in claims 1-20 of U.S. Patent No. 11,642,373 anticipate or encompass the pharmaceutical composition in the application being examined and, therefore, a patent to the genus would, necessarily, extend the rights of the species or sub- should the genus issue as a patent after the species of sub-genus.
Amended claims 42 and 44-45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47 and 58-61 of copending Application No. 19/257,953 (reference application) in view of Fong et al (WO 2006/047569) and Cui et al (US 2008/0089875; IDS).
The instant claims differ from claims 47 and 58-61 of copending Application No. 19/257,953 in reciting specifically at least the limitations “a granulocyte precursor cell derived ex vivo from a haematopoietic cell, wherein the granulocyte precursor cell is selected from a neutrophilic promyelocyte, a neutrophilic myelocyte, a neutrophilic metamyelocyte, a neutrophilic band cell, or a combination thereof; and b. a carrier” and “wherein the haematopoietic cell is derived from a donor that produces granulocytes that kill at least 5% of cancer cells in a cancer killing assay”. It is noted that dependent claim 60 of copending Applicantion No. 19/257,953 already recites the limitation “wherein the granulocyte precursor cells are promyelocytes, myelocytes, intermediates thereof, or combinations thereof”.
Before the effective filing date of the present application (10/25/2017), Fong et al already disclosed at least a therapeutic composition comprising an ex vivo cultured expanded population of myeloid progenitor cells and a pharmaceutically acceptable medium, wherein the starting/initial cell population includes hematopoietic stem cells that are derived from an allogeneic donor or from a plurality of allogeneic donors (Abstract; Summary; particularly paragraphs [0013], [0015]-[0016], and [00112]-[00114]). Fong et al also taught that expanded myeloid progenitor cells generally comprise common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP) (paragraph [0022]), and that the myeloid progenitor cells were generated and expanded by contacting hematopoietic stem cells with a culture medium comprising a cytokine and growth factor mixture that includes G-CSF and GM-CSF (paragraph [0018]). Fong et al disclosed that G-CSF acts to induce the bone marrow to produce granulocytes, and promote the survival, proliferation, differentiation and function of neutrophil granulocyte progenitor cells and mature neutrophils (paragraph [00120]), and stated “In instances where more mature cells of the myeloid lineage are desired to enhance immediate protection against neutropenia and/or thrombocytopenia, the cytokines G-CSF or GM-CSF is added to the foregoing cytokine mixture. This may be done after an initial period of growth in media lacking G-CSF or GM-CSF to permit expansion of more primitive myeloid progenitor cells prior to promoting differentiation into the progenitor cells that are further along in the myeloid lineage” (paragraph [00131]).
Additionally, Cui et al already taught a method of treating cancer using allogeneic white blood cells, particularly innate immune cells (e.g., granulocytes such as neutrophils, basophils and eosinophils), that are obtained from a healthy allogeneic donor and are screened for ability to kill cancer cells in vitro (Abstract; Summary of the Invention; particularly paragraphs [0005]-[0007], [0014], [0018]; and Examples 1-3). Cui et al stated “After sampling a group of volunteers using this unique blood test, it was found that healthy humans had a wide range of cancer-cell-killing activity (CKA; FIG. 1). On a 0% to 100% scale, WBCs from many healthy humans had significant levels of naturally-present activity ranging between 40% and 60%, with some as high as that of cancer-resistant mice at levels of 70% to 90%...Overall, healthy persons had a higher CKA than their age-matched counterparts whom had cancer. Intriguingly, individuals over the age of 50 also demonstrated an overall lower CKA than a younger comparison group” (paragraph [034]); “Separation of white blood cells into granulocyte and agranulocyte types indicated that the CKA was present in the granulocyte fraction (FIG. 2C)” (paragraph [0045]); and “Given that in vitro CKA for WBCs was attributed to the granulocyte fraction, the in vivo CKA of granulocytes is expected to be useful in the treatment of cancer” (paragraph [0046]).
Accordingly, it would have been obvious for an ordinary skilled artisan before the effective filing date of the present application to modify the pharmaceutical composition in claims 47 and 58-61 of copending Application No. 19/257,953 by also obtaining a granulocyte precursor cell such as a neutrophilic promyelocyte derived ex vivo from a haematopoietic cell of a young healthy donor, including from a donor that produces granulocytes that kill at least 5% of cancer cells in a cancer killing assay, and including a pharmaceutically acceptable carrier in the pharmaceutical composition; in light of the teachings of Fong et al and Cui et al as set forth above with a reasonable expectation of success.
An ordinary skilled artisan would have been motivated to carry out the above modifications because: (i) Fong et al already disclosed at least a therapeutic composition comprising an ex vivo cultured expanded population of myeloid progenitor cells and a pharmaceutically acceptable medium, wherein the starting/initial cell population includes hematopoietic stem cells that are derived from an allogeneic donor or from a plurality of allogeneic donors; and the expanded myeloid progenitor cells generally comprise common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP); and (ii) Cui et al also taught successfully a method of treating cancer using allogeneic white blood cells, particularly innate immune cells (e.g., granulocytes such as neutrophils, basophils and eosinophils), that are obtained from a healthy allogeneic donor and are screened for ability to kill cancer cells in vitro; and established that the CKA (cancer-cell-killing activity) was present in the granulocyte fraction. Moreover, Cui et al stated “After sampling a group of volunteers using this unique blood test, it was found that healthy humans had a wide range of cancer-cell-killing activity (CKA; FIG. 1). On a 0% to 100% scale, WBCs from many healthy humans had significant levels of naturally-present activity ranging between 40% and 60%, with some as high as that of cancer-resistant mice at levels of 70% to 90%...Overall, healthy persons had a higher CKA than their age-matched counterparts whom had cancer. Intriguingly, individuals over the age of 50 also demonstrated an overall lower CKA than a younger comparison group” (paragraph [034]). Additionally, the resulting modified pharmaceutical composition would be useful as a source of granulocytes for cancer treatment.
The modified pharmaceutical composition resulting from claims 47 and 58-61 of copending Application No. 19/257,953 along with teachings of Fong et al and Cui et al is indistinguishable and encompassed by the presently claimed invention.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection.
Amended claims 42 and 44-45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 48-52 of copending Application No. 17/785,012 (reference application) in view of Fong et al (WO 2006/047569) and Cui et al (US 2008/0089875; IDS).
The instant claims differ from claims 48-52 of copending Application No. 17/785,012 in reciting specifically at least the limitations “a granulocyte precursor cell derived ex vivo from a haematopoietic cell, wherein the granulocyte precursor cell is selected from a neutrophilic promyelocyte, a neutrophilic myelocyte, a neutrophilic metamyelocyte, a neutrophilic band cell, or a combination thereof” and “wherein the haematopoietic cell is derived from a donor that produces granulocytes that kill at least 5% of cancer cells in a cancer killing assay”. It is noted that stem cells in claims 48-52 of copending Application No. 17/785,012 encompass a precursor cell (see dependent claim 52).
Before the effective filing date of the present application (10/25/2017), Fong et al already disclosed at least a therapeutic composition comprising an ex vivo cultured expanded population of myeloid progenitor cells and a pharmaceutically acceptable medium, wherein the starting/initial cell population includes hematopoietic stem cells that are derived from an allogeneic donor or from a plurality of allogeneic donors (Abstract; Summary; particularly paragraphs [0013], [0015]-[0016], and [00112]-[00114]). Fong et al also taught that expanded myeloid progenitor cells generally comprise common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP) (paragraph [0022]), and that the myeloid progenitor cells were generated and expanded by contacting hematopoietic stem cells with a culture medium comprising a cytokine and growth factor mixture that includes G-CSF and GM-CSF (paragraph [0018]). Fong et al disclosed that G-CSF acts to induce the bone marrow to produce granulocytes, and promote the survival, proliferation, differentiation and function of neutrophil granulocyte progenitor cells and mature neutrophils (paragraph [00120]), and stated “In instances where more mature cells of the myeloid lineage are desired to enhance immediate protection against neutropenia and/or thrombocytopenia, the cytokines G-CSF or GM-CSF is added to the foregoing cytokine mixture. This may be done after an initial period of growth in media lacking G-CSF or GM-CSF to permit expansion of more primitive myeloid progenitor cells prior to promoting differentiation into the progenitor cells that are further along in the myeloid lineage” (paragraph [00131]).
Additionally, Cui et al already taught a method of treating cancer using allogeneic white blood cells, particularly innate immune cells (e.g., granulocytes such as neutrophils, basophils and eosinophils), that are obtained from a healthy allogeneic donor and are screened for ability to kill cancer cells in vitro (Abstract; Summary of the Invention; particularly paragraphs [0005]-[0007], [0014], [0018]; and Examples 1-3). Cui et al stated “After sampling a group of volunteers using this unique blood test, it was found that healthy humans had a wide range of cancer-cell-killing activity (CKA; FIG. 1). On a 0% to 100% scale, WBCs from many healthy humans had significant levels of naturally-present activity ranging between 40% and 60%, with some as high as that of cancer-resistant mice at levels of 70% to 90%...Overall, healthy persons had a higher CKA than their age-matched counterparts whom had cancer. Intriguingly, individuals over the age of 50 also demonstrated an overall lower CKA than a younger comparison group” (paragraph [034]); “Separation of white blood cells into granulocyte and agranulocyte types indicated that the CKA was present in the granulocyte fraction (FIG. 2C)” (paragraph [0045]); and “Given that in vitro CKA for WBCs was attributed to the granulocyte fraction, the in vivo CKA of granulocytes is expected to be useful in the treatment of cancer” (paragraph [0046]).
Accordingly, it would have been obvious for an ordinary skilled artisan before the effective filing date of the present application to modify the pharmaceutical composition in claims 48-52 of copending Application No. 17/785,012 by also obtaining a granulocyte precursor cell such as a neutrophilic promyelocyte derived ex vivo from a haematopoietic cell of a young healthy donor, including from a donor that produces granulocytes that kill at least 5% of cancer cells in a cancer killing assay; in light of the teachings of Fong et al and Cui et al as set forth above with a reasonable expectation of success.
An ordinary skilled artisan would have been motivated to carry out the above modifications because: (i) Fong et al already disclosed at least a therapeutic composition comprising an ex vivo cultured expanded population of myeloid progenitor cells and a pharmaceutically acceptable medium, wherein the starting/initial cell population includes hematopoietic stem cells that are derived from an allogeneic donor or from a plurality of allogeneic donors; and the expanded myeloid progenitor cells generally comprise common myeloid progenitor cells (CMP), granulocyte/macrophage progenitor cells (GMP), and megakaryocyte/erythroid progenitor cells (MEP); and (ii) Cui et al also taught successfully a method of treating cancer using allogeneic white blood cells, particularly innate immune cells (e.g., granulocytes such as neutrophils, basophils and eosinophils), that are obtained from a healthy allogeneic donor and are screened for ability to kill cancer cells in vitro; and established that the CKA (cancer-cell-killing activity) was present in the granulocyte fraction. Moreover, Cui et al stated “After sampling a group of volunteers using this unique blood test, it was found that healthy humans had a wide range of cancer-cell-killing activity (CKA; FIG. 1). On a 0% to 100% scale, WBCs from many healthy humans had significant levels of naturally-present activity ranging between 40% and 60%, with some as high as that of cancer-resistant mice at levels of 70% to 90%...Overall, healthy persons had a higher CKA than their age-matched counterparts whom had cancer. Intriguingly, individuals over the age of 50 also demonstrated an overall lower CKA than a younger comparison group” (paragraph [034]). Additionally, the resulting modified pharmaceutical composition would be useful as a source of granulocytes for cancer treatment.
The modified pharmaceutical composition resulting from claims 48-52 of copending Application No. 17/785,012 along with teachings of Fong et al and Cui et al is indistinguishable and encompassed by the presently claimed invention.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
This is a provisional nonstatutory double patenting rejection.
It is noted that in the Amendment dated 12/23/2025 (pages 8-9), Applicant simply requested all of the above nonstatutory double patenting rejections be held in abeyance until allowable subject matter is identified.
Conclusions
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Quang Nguyen, Ph.D., whose telephone number is (571) 272-0776.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s acting SPE, James Douglas (Doug) Schultz, Ph.D., may be reached at (571) 272-0763.
To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Group Art Unit 1631; Central Fax No. (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
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/QUANG NGUYEN/Primary Examiner, Art Unit 1631