DETAILED ACTION
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 response and amendments received June 3, 2026 are acknowledged.
Claim 4 has been amended.
Claims 1-13 are pending in the instant application.
Applicant’s election without traverse of the invention of group I, drawn to human macrophages, and the species of macrophages comprising biallelically mutated MAF and MAFB genes with such cells having upregulated HLA-DRB5, downregulated DNASE I, being HLA-DRA+ and CD28-, in the reply filed on June 3, 2026 is acknowledged.
Claims 11-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 3, 2026.
Claims 1-10 are under examination as they read upon the species of human macrophages comprising biallelic mutations to both MAF and MAFB.
Information Disclosure Statement
The IDS forms received 2/3/2025 and 4/16/2026 are acknowledged and the references cited therein have been considered.
The listing of references in the specification on pages 5-6 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 § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-10 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant has claimed human macrophages which must contain at least one mutation in both alleles of a chromosomal gene, wherein such mutations reasonably result in the macrophage being resistant to M-2 polarization induced by M-CSF exposure. The broadest claims allow for such mutations to be anywhere in the genome, with dependent claim 7 requiring the deletion to be in at least one gene selected from a Markush group. To support such claims, applicant discloses the prior art of Aziz from 2009 concerning data from MAF, MAFB double knockout mice, applicant’s own data from double knockout mice (examples 1-8) and the generation of human double knockouts from iPSC (examples 9-14). Notably, all such data, both human and mouse, involved the deletion of MAF and MAFB genes and data demonstrating that other deletions, such as those genes recited in claim 7 also give rise to the same cell populations has not been provided.
However, page 33 of the instant specification provides the following guidance concerning human cells:
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Thus, applicant’s own specification teaches that if genes other than MAF and MAFB are deleted, macrophage function may be compromised and/or differentiation of cells into macrophages may be impossible. Based applicant’s own teachings as quoted above, artisans would not reasonably expect any gene deletion, whether recited in claim 7 or not to actually work in making macrophages resistant to M2 polarizations unless such genes were MAF and MAFB as demonstrated by the working examples in both humans and mice.
Therefore, in view of the breadth of the claims, the teachings of the art, and the guidance and direction of the instant specification, artisans would not reasonably be able to make and use that which is presently claimed unless the deletions were limited to only be in MAF and MAFB. Given that the instant specification disclose that deletions to other genes are expected to impair macrophage differentiation and/or effector functions, artisans would need to perform additional unpredictable undue basic science research and experimentation to find and validate genes that can be deleted while maintaining the recited functional activities.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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.
Claims 1-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sieweke et al. (WO 2008/084069).
Sieweke et al. methods for making monocytes which lack expression of Maf and MafB due to generic deletion and the administration of such cells to treat cancer (see entire document, particularly the abstract, claims, and pages 19-24 most particularly claims 7 and 14). Notably, such cells are disclosed as being human (see particularly claim 9). Sieweke et al. disclose that “Inhibition of the expression or the activity of c-Maf and MafB may be achieved by any technique (see particularly lines 34-35 of page 14), disclose transient techniques including antisense and siRNA, and provide a working example wherein MafB-/-,c-Maf-/- were created and displayed a macrophage phenotype even after extended culturing in the presence of M-CSF (see the working example, most particularly Figure 5). Note that Sieweke et al. disclose that it is routine in the art to adjust the number of cells administered based upon the disease in question and route of administration (see particularly lines 6-22 of page 24) and administered 1x106 double knockout cells as part of their experiments as disclosed in the working example (see particularly page 35).
It is noted that while Sieweke et al. disclose assays to determine the function of their macrophages after exposure to M-CSF, such assays dis not include measuring mRNA levels for various marker proteins. However, as presently recited claim 2 (and all claims depending therefrom) simply require the macrophages to have been exposed to M-CSF. The claims do not recite process steps wherein the various mRNA are required to be measured or compared to control values. As such claims 3-6 are most properly construed as reciting the intended results of exposing double knockout macrophages to M-CSF, and note that such intended results do not change the product, i.e. a double knockout macrophage exposed to M-CSF, into anything that is structurally different from that which is recited in claim 2. See also MPEP 2111.02(II). Similarly, claim 1 recites that the knockout macrophage is resistant to M2 polarization, which is also a statement of what applicant expects to occur (i.e. intended results), and given that Sieweke et al. actually made and claimed double knockout cells identifying that such cells are resistant to polarization reasonably can additionally be view as further characterization of a known product. Indeed, as per MPEP 2112, "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
Therefore, the prior art anticipates that which is presently claimed.
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 and 7-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 8,691,964. Although the claims at issue are not identical, they are not patentably distinct from each other because the issued claims anticipate that which is presently claimed.
The issued claims recite human macrophages which do not express Maf and MafB because their genes have been deleted (see all issued claims, most particularly claims 1, 2, and 4). Given that the gene or genes deleted in the instant claimed cells are either totally generic (claim 1) or are to be selected form a Markush group (claim 7) the issued claims are more narrowly constructed and thus anticipate the breadth of what is presently claimed.
Claims 2-6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 8,691,964 as applied to claims 1 and 7-9 above and further in view of Sieweke et al. (WO 2008/084069).
The inventions anticipated by the issued claims have bene discussed above and differ from that which is presently claimed in that even though the issued claims recite that the macrophages are expanded in the presence of a cytokine (see particularly issued claim 8) the cytokine is not recited as being M-CSF, and the number of cells is not recited as being at least a million.
Sieweke et al. methods for making monocytes which lack expression of Maf and MafB due to generic deletion and the administration of such cells to treat cancer (see entire document, particularly the abstract, claims, and pages 19-24 most particularly claims 7 and 14). Notably, such cells are disclosed as being human (see particularly claim 9). Sieweke et al. disclose that “Inhibition of the expression or the activity of c-Maf and MafB may be achieved by any technique (see particularly lines 34-35 of page 14), disclose transient techniques including antisense and siRNA, and provide a working example wherein MafB-/-,c-Maf-/- were created and displayed a macrophage phenotype even after extended culturing and expansion in the presence of M-CSF for months (see the working example, most particularly page 33 and Figure 5). Note that Sieweke et al. disclose that it is routine in the art to adjust the number of cells administered based upon the disease in question and route of administration (see particularly lines 6-22 of page 24) and administered 1x106 double knockout cells as part of their experiments as disclosed in the working example (see particularly page 35).
Therefore, it would have been obvious to ordinary artisans at the time of the invention to use M-CSF as the cytokine used for expanding the double knockout macrophages of the issued claims. This is because Sieweke et al. disclose that M-CSF causes significant expansion of MAF, MAFB double knockout macrophages even over a time period of many months.
It is noted that neither the issued claims nor Sieweke et al. disclose measuring mRNA levels for various marker proteins. However, as presently recited instant claim 2 (and all claims depending therefrom) simply require the macrophages to have been exposed to M-CSF. The claims do not recite process steps wherein the various mRNA are required to be measured or compared to control values. As such claims 3-6 are most properly construed as reciting the intended results of exposing double knockout macrophages to M-CSF, and note that such intended results do not change the product, i.e. a double knockout macrophage exposed to M-CSF, into anything that is structurally different from that which is recited in claim 2. See also MPEP 2111.02(II).
Claims 1 and 7-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of copending Application No. 18/551,385. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate that which is presently claimed.
Specifically, copending claim 1 recites a human macrophage cell that is non-tumorigenic and comprises biallelic deletions in both MAF and MAFB genes. Dependent claims indicate that such cells number at least one million (i.e. 1x106) and are to be administered for therapeutic use (see particularly copending claims 7 and 9). Given that none of the instant claims recite claims that necessarily require the knockout of both MAF and MAFB, the copending claims are more narrow, and therefore anticipate, the breadth of what is presently claimed.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 2-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of copending Application No. 18/551,385 as applied to claims 1 and 7-10 above, and further in view of Sieweke et al. (WO 2008/084069).
The inventions anticipated by the copending claims have been discussed above and differ from that which is presently claimed in that while the copending claims recite culturing the double knockout human macrophages in under conditions suitable for growth (see for example copending claims 6-8), such conditions are not recited as comprising M-CSF.
Sieweke et al. methods for making monocytes which lack expression of Maf and MafB due to generic deletion and the administration of such cells to treat cancer (see entire document, particularly the abstract, claims, and pages 19-24 most particularly claims 7 and 14). Notably, such cells are disclosed as being human (see particularly claim 9). Sieweke et al. disclose that “Inhibition of the expression or the activity of c-Maf and MafB may be achieved by any technique (see particularly lines 34-35 of page 14), disclose transient techniques including antisense and siRNA, and provide a working example wherein MafB-/-,c-Maf-/- were created and displayed a macrophage phenotype even after extended culturing and expansion in the presence of M-CSF for months (see the working example, most particularly page 33 and Figure 5). Note that Sieweke et al. disclose that it is routine in the art to adjust the number of cells administered based upon the disease in question and route of administration (see particularly lines 6-22 of page 24) and administered 1x106 double knockout cells as part of their experiments as disclosed in the working example (see particularly page 35).
Therefore, it would have been obvious to ordinary artisans at the time of the invention to use M-CSF in the media used for expanding the double knockout macrophages of the copending claims. This is because Sieweke et al. disclose that M-CSF causes significant expansion of MAF, MAFB double knockout macrophages even over a time period of many months.
It is noted that neither the copending claims nor Sieweke et al. disclose measuring mRNA levels for various marker proteins. However, as presently recited claim 2 (and all claims depending therefrom) simply require the macrophages to have been exposed to M-CSF. The claims do not recite process steps wherein the various mRNA are required to be measured or compared to control values. As such claims 3-6 are most properly construed as reciting the intended results of exposing double knockout macrophages to M-CSF, and note that such intended results do not change the product, i.e. a double knockout macrophage exposed to M-CSF, into anything that is structurally different from that which is recited in claim 2. See also MPEP 2111.02(II).
This is a provisional nonstatutory double patenting rejection.
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michael Szperka whose telephone number is (571)272-2934. The examiner can normally be reached Monday-Friday 8:30-5:00.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
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