DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. PCT/EP2020/073396, filed on 08/20/2020.
Election/Restrictions
Applicant’s election without traverse of species; (A) single cell population to produce is (a) haemogenic endothelial cells (HECs); (B) T-cell population is (b) CD8+; and (C) single cell to introduce to a heterologous nucleic acid is (a) induced pluripotent stem cells (iPSCs); in the reply filed on 11/21/2024 is acknowledged.
Claim Status
In the reply filed on Nov. 21, 2024, Applicant has amended claims 2-3, 5, 17, 24, 31-32, 34-35, 37-38, 41-43, 44, 47-49, 52-53, and canceled claims 4, 6-16, 18-23, 25-30, 33, 36, 39-40, 45-46, 50-51, 54-56.
Currently, claims 1-3, 5, 17, 24, 31-32, 34-35, 37-38, 41-43, 44, 47-49, and 52-53 are under examination.
Claim Objections
Claims 1, 5, 17, and 24 are objected to because of the following informalities: the abbreviations are not followed by the spelling of the words at least for the first recitation. For example, claim 5 should have the words “fibroblast growth factor” followed by the abbreviation of “FGF”. This would occur in the claim where the abbreviation “FGF” is first introduced. Appropriate correction is required.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on Jan. 27, 2022 and Sept. 24, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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 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.
Claims 1-3, 17, 31-32, 34-35, 37-38, 41-44, 47, 49, and 52-53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Valamehr et al., (WO2017/078807A1, published 2017, cited IDS 1/27/22; hereinafter as “Valamehr”).
Regarding claim 1, Valamehr discloses a method of producing a population of haemogenic progenitor cells comprising; (i) differentiating a population of induced pluripotent stem cells (iPSCs) into mesoderm cells and; (ii) differentiating the mesoderm cells to produce a population of haemogenic progenitor cells wherein steps (i) and (ii) are performed without purification or isolation of cells in the population (See e.g. abstract, claim 1, Examples 2-3).
Regarding claim 2, Valamehr discloses wherein steps (i) and (ii) are performed in the absence of stromal cells or serum (See e.g. para. 5-6, 177-178 and 180).
Regarding claim 3, Valamehr discloses wherein the haemogenic progenitor cells are haemogenic endothelial cells (HECs) or haematopoietic progenitor cells (HPCs)(see e.g. abstract, claim s 1-2).
Regarding claim 17, Valamehr discloses wherein the mesoderm cells are differentiated into HECs by culturing the population of mesoderm cells to promote haemogenic endothelial (HE) differentiation; wherein the HE induction medium comprises SCF and/or VEGF (see e.g. para. 15).
Regarding claim 31 and 34, Valamehr discloses wherein the haemogenic progenitor cells are HPCs and the method further comprises differentiating the population of HPCs into progenitor T cells, and the produce a population of T cells (See e.g. para. 220-221 and 323).
Regarding claim 32, culturing the population of HPCs in a lymphoid expansion medium (i.e. SCF, FLT3L, TPO and IL7) to produce the progenitor T cells (see e.g. paras. 12-13, 164, 220-221 and 323; claims 14, 84 and 104). Claim Interpretation Broadest Reasonable interpretation: the specification teaches the lymphoid expansion medium may comprise SCF, FLT3L, TPO and IL7 [See specification page 16, lns 13-17]. Thus, the media as taught by Valamehr reads on the lymphoid expansion medium as claimed
Regarding claim 35, Valamehr discloses wherein the progenitor T cells are matured by a method comprising culturing the population of progenitor T cells in a T cell maturation medium (i.e. SCF, FLT3L, and IL7) to produce the T cells (see e.g. paras. 12-13, 164, 220-221 and 323; claims 84 and 104). Claim Interpretation Broadest Reasonable interpretation: the specification teaches the maturation medium may comprise SCF, FLT3L, and IL7 [See specification page 17, lns 33-34]. Thus, the media as taught by Valamehr reads on the lymphoid expansion medium as claimed
Regarding claim 37, Valamehr discloses activating and expanding the T cells to produce a population of T cells have a CD8+ single positive phenotype (see e.g. par. 349, 389 Example 14, claim 131).
Regarding claim 38, Valamehr discloses wherein the T cells specifically bind to cells expressing a target antigen (i.e. tumor antigen) (see e.g. para. 137). Claim Interpretation Broadest Reasonable interpretation: the specification teaches that the target antigen may be a tumor antigen [See Spec. page 20, ln 7-9).
Regarding claim 41, Valamehr discloses wherein the iPSCs are derived from T cells obtained from a donor individual (see e.g. para. 134).
Regarding claim 42, Valamehr discloses wherein the T cells obtained from the donor individual are specific for the target antigen (i.e. tumor antigen)(see e.g. para. 323, Example 9). Claim Interpretation Broadest Reasonable interpretation: the specification teaches that the target antigen may be a tumor antigen [See Spec. page 20, ln 7-9).
Regarding claim 43, Valamehr discloses wherein the T cells obtained from the donor individual are tumour-infiltrating lymphocytes (TILs)(see e.g. para. 163)
Regarding claim 44 and 47, Valamehr discloses introducing heterologous nucleic acid (i.e. genetically modified) encoding an antigen receptor into the iPSCs that is donor or patient specific (see e.g. para. 384, 381, Example 9). Further, Valamehr discloses wherein the heterologous nucleic acid is incorporated into the genome of the iPSCs (i.e. genome editing)(see e.g. para. 43, 45, 383, claim 2, 62).
Regarding claim 49, Valamehr discloses wherein the antigen receptor is a TCR (see e.g. para. 374).
Regarding claim 52, Valamehr discloses wherein the TCR binds specifically to a peptide thereof expressed by cells independently of MHC presentation (i.e. CD Id-restricted T cells)(see e.g. para. 168).
Regarding claim 53, Valamehr discloses a surface trigger receptor where the surface triggering receptor facilitates bi- or multi- specific antibody engagement between the effector cells and specific target cell e.g. a tumor cell, corresponding to the claim limitation of binding specifically to a tumour antigen expressed by cancer cells (i.e. tumor cells) independently of MHC presentation (see e.g. para. 137).
Accordingly, Valamehr et al anticipates instant claims.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Valamehr et al., (WO2017/078807A1, published 2017, cited IDS 1/27/22; hereinafter as “Valamehr”), as applied to claims 1-3, 17, 31-32, 34-35, 37-38, 41-44, 47, 49, and 52-53 above, and further in view of Slukvin, et al. (US9938499B2, published 2018, cited IDS 1/27/22; hereinafter as “Slukvin”).
The teachings of Valamehr apply here as indicated above.
Regarding claim 5, Valamehr teaches wherein the iPSCs are cultured sequentially in first, second and third mesoderm induction media to induce differentiation into mesoderm cells, wherein; the first mesoderm induction medium comprises activin, the second mesoderm induction medium comprises BMP, and FGF; and the third mesoderm induction medium comprises activin, BMP, FGF, and a GSK3 inhibitor (see e.g. paras. 12-13), as discussed above.
Valamehr is silent regarding the second mesoderm induction medium comprising activin.
However, Slukvin teaches an xenogen-free and serum albumin-free method with activin for differentiating human pluripotent stem cells into mesoderm cells (see e.g. abstract, and claim 1).
Regarding claim 5, Slukvin teaches a method for culturing the human pluripotent stem cells under hypoxic conditions in a cell culture medium comprising FGF, BMP, and Activin A (see e.g. claim 1, 7 and 10; Table 3; Example 3).
Accordingly, it would have been obvious to prepare a mesoderm induction medium that comprises BMP and FGF (as taught by Valamehr) with activin (as taught by Slukvin) because Slukvin teaches that during embryonic development TGFβ/Nodal/Activin A signaling is critical to initiate primitive streak formation and subsequent mesoderm development (see e.g. Example 3). Additionally, Valamehr and Slukvin both teach a method for differentiation iPSC into mesoderm cells. Further, Valamehr and Slukvin both teach serum free conditions, as discussed above. Thus, it could have been done with a reasonable expectation of success.
Hence, the claimed invention as a whole was prima facie obvious.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Valamehr et al., (WO2017/078807A1, published 2017, cited IDS 1/27/22; hereinafter as “Valamehr”) in view of as applied to claims 1-3, 17, 31-32, 34-35, 37-38, 41-44, 47, 49, and 52-53 above, and further in view Daley, et al. (WO2018/232079 A1, published 2018; hereinafter as “Daley”),
The teachings of Valamehr apply here as indicated above.
Valamehr is silent regarding the haematopoietic induction medium comprises Sonic hedgehog (SHH), angiotensin II, and an angiotensin II type 1 receptor (AT1) antagonist.
However, Daley teaches culturing haemogenic endothelial cells (HECs) into haematopoietic progenitor cells (HPCs) (see e.g. abstract, claim 1 and claim 17).
Regarding claim 24, Daley teaches the culture medium with Sonic hedgehog (SHH), angiotensin II, and an angiotensin II type 1 receptor (AT1) antagonist (i.e. AGTR1) (see e.g. para. 71 and 291-293).
Accordingly, it would have been obvious for one of ordinary skill in the art to modify the methods of Valamehr with the haematopoietic induction medium factors of SHH, angiotensin II, and AGTR1 (as taught by Daley) because Daley teaches that SHH, angiotensin II, and AGTR1 are required for efficient Endothelial-to-hematopoietic transition (EHT)(see e.g. para. 293). Thus, a person of ordinary skill in the art would have been motivated to have the factors (i.e. SHH, angiotensin II, and AGTR1) present in the culture medium in order to obtain the maximum amount of haemogenic progenitor cells (HPCs). Further, Valamehr and Daley both teach methods of producing haemogenic progenitor cells (HPCs). Thus, it could have been done with a reasonable expectation of success.
Hence, the claimed invention as a whole was prima facie obvious.
Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over Valamehr et al., (WO2017/078807A1, published 2017, cited IDS 1/27/22; hereinafter as “Valamehr”), as applied to claims 1-3, 17, 31-32, 34-35, 37-38, 41-44, 47, 49, and 52-53 above, and further in view of Valamehr et al., (US2018/0155717, published 2018; hereinafter as “the ‘717 application”).
The teachings of Valamehr apply here as indicated above.
Regarding claim 48, Valamehr teaches iPSCs may transduced with a lentivirus (see e.g. para. 371, 375). Further, Valamehr discloses “genomically engineered iPSCs can also be generated during or after reprogramming somatic cells, using methods, for example, disclosed in the U.S. Application Serial Nos. 62/251,032 and 62/337,258 (i.e. US2018/0155717 A1), which are incorporated by reference in their entirety” (see para. 322).
Valamehr is silent regarding the gene editing system is an adeno-associated virus (AAV).
However, Valamehr references the ‘717 application, which teaches genome-engineered iPSCs, and derivative cells with stable and functional genome editing at selected sites (see e.g. abstract).
Regarding claim 48, the ‘717 application, teaches genome editing by CRISPR/cas9 (see e.g. para. 56) or AAV (see e.g. para. 162).
Accordingly, it would have been obvious for one of ordinary skill in the art to modify the methods of Valamehr with the gene editing systems of CRISPR/cas9 or AAV (as taught by the ‘717 application) because the ‘717 application teaches method for obtaining genome-engineered iPSCs, and derivative cells with stable and functional genome editing at selected sites (see e.g. abstract). Further, Valamehr references the ‘717 application and discloses that a person of ordinary skill in the art would be able to genomically engineered iPSCs with methods that were known in the prior art (see para. 322 of Valamehr). Thus, it would have been done with a reasonable expectation of success.
Hence, the claimed invention as a whole was prima facie obvious.
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.
Claims 1, 3, 5, 16-17, 24, 31-32, 38, 41, 43-44, 47-49, and 52-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 17-18, 22, 34, 39, 40, 48-50, 53-55, 57-58, and 66 of co-pending Application No. U.S. Patent No. 17/630,880 (hereinafter as the “‘880 application”).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the co-pending application disclose a species of the instant claims.
The co-pending application claims recite: A method of producing a population of haematopoietic progenitor cells (HPCs) comprising; (i) culturing a population of haemogenic endothelial cells (HECs) in a haematopoietic induction medium to produce a population of haematopoietic progenitor cells (HPCs ), wherein the haematopoietic induction medium comprises one or both of SCF and VEGF (claim 1), and “wherein the population of HECs is produced in vitro from induced pluripotent stem cells (iPSCs)”(claim 16).
While the instant invention recites: “A method of producing a population of haemogenic progenitor cells comprising; (i) differentiating a population of induced pluripotent stem cells (iPSCs) into mesoderm cells and; (ii) differentiating the mesoderm cells to produce a population of haemogenic progenitor cells wherein steps (i) and (ii) are performed without purification or isolation of cells in the population” (claim 1), and “mesoderm cells are differentiated into HECs by culturing the population of mesoderm cells to promote haemogenic endothelial (HE) differentiation; wherein the HE induction medium comprises SCF and/or VEGF (claim 17).
Thus, the co-pending claims encompass a method of producing a population of haemogenic progenitor cells(HPCs) of claim 1. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 3, the ‘880 application recites a method of producing a population of haematopoietic progenitor cells (HPCs) comprising; (i) culturing a population of haemogenic endothelial cells (HECs) in a haematopoietic induction medium to produce a population of haematopoietic progenitor cells (HPCs),(claim 1).
Regarding claim 5, the ‘880 application recites the iPSCs are cultured sequentially in first, second and third mesoderm induction media to induce differentiation into mesoderm cells, wherein; the first mesoderm induction medium comprises activin, the second mesoderm induction medium comprises activin, BMP, and FGF; and the third mesoderm induction medium comprises activin, BMP, FGF, and a GSK3 inhibitor (claim 22).
Regarding claim 17, the ‘880 application recites wherein the mesoderm cells are differentiated into HECs by culturing the population of mesoderm cells in an HE induction medium to induce differentiation into HECs; wherein the HE induction medium comprises SCF and VEGF (claim 34).
Regarding claim 24, the ‘880 application recites wherein the haematopoietic induction medium comprises ill VEGF, SCF, Thrombopoietin (TPO), Flt3 ligand (Flt3L), IGF-1, IL-3 and IL-6; or (ii) VEGF, SCF, Thrombopoietin (TPO), Flt3 ligand (Flt3L), IGF-1, IL-3, IL-6, and IL-7 (claim 5 and 66).
Regarding claim 31, the ‘880 application recites wherein the haemogenic progenitor cells are HPCs and the method further comprises differentiating the population of HPCs into progenitor T cells (claim 39).
Regarding claim 32, the ‘880 application recites wherein the HPCs are differentiated by a method comprising culturing the population of HPCs in a lymphoid expansion medium to produce the progenitor T cells (claim 40).
Regarding claim 37, the ‘880 application recites activating and expanding the T cells to produce a population of T cells have a CD8+ single positive phenotype or a CD4+ single positive phenotype (claim 42).
Regarding claim 38, the ‘880 application recites wherein the iPSCs are derived from T cells obtained from a donor individual that are specific for the target antigen (claim 48).
Regarding claim 41, the ‘880 application recites wherein the iPSCs are derived from T cells obtained from a donor individual (claim 18).
Regarding claim 43, the ‘880 application recites wherein the T cells obtained from the donor individual are tumour-infiltrating lymphocytes (TILs)(claim 49).
Regarding claim 44, the ‘880 application recites introducing heterologous nucleic acid encoding an antigen receptor into the iPSCs, HPCs or progenitor T cells (claim 50).
Regarding claim 47, the ‘880 application recites wherein the heterologous nucleic acid is incorporated into the genome of the iPSCs, HECs, haemogenic progenitor cells, or progenitor T cells using a gene editing system (claim 53).
Regarding claim 48, the ‘880 application recites wherein the gene editing system is CRISPR/Cas9 or AAV (claim 54).
Regarding claim 49, the ‘880 application recites wherein the antigen receptor is a TCR (claim 55).
Regarding claim 52, the ‘880 application recites wherein the TCR binds specifically to an MHC displaying a peptide fragment of a target antigen expressed by cells or specifically binds to a target antigen or peptide thereof expressed by cells independently of MHC presentation (claim 57).
Regarding claim 53, the ‘880 application recites wherein the TCR binds specifically to an MHC displaying a peptide fragment of a tumour antigen expressed by the cancer cells or binds specifically to a tumour antigen or peptide fragment thereof expressed by cancer cells independently of MHC presentation (claim 58).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPHINE GONZALES whose telephone number is (571)272-1794. The examiner can normally be reached M-Th: 9AM - 5:00PM (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPHINE M GONZALES/ Examiner, Art Unit 1631
/J. E. ANGELL, Ph.D./Primary Examiner, Art Unit 1637