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 .
Claims 36-42 are added.
Newly submitted claims 41-42 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: The examined invention is a method of making THEM cells and the THEMs. Newly added claims 41-42 are drawn to method of using the THEMs in regenerative medicine using THEMs, according to claim 28. THEMs are not a contribution over the prior art of Mazzone (WO2013/110817) and therefore claims 41-42 lack unity of invention with the already-examined subject matter
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 41-42 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Claims 28-40 are under consideration.
Claim 24 is objected to because of the following informalities: Claim 24 has a period in line4, needs a space at line 5 in “to10 days” and needs the “[“ removed from line 6. Appropriate correction is required.
Claim 27 is objected to because of the following informalities: Claim 27 has a comma at the end of line 4 that does not appear to belong there. Appropriate correction is required.
Claim 28 is objected to because of the following informalities: Claim 28 contains some grammatical issues such as “is intended a gene expression level” and “expression the housekeeping”. It appears some words were omitted. Appropriate correction is required.
**It is noted that the language of claim 29 has been amended to read more precisely on the invention. Similar language remains in claim 28. Claim 28 would benefit from language similar to that of claim 29
Claim 31 is recommended to read “low or no” in place of low/no. Some claims have this change.
Claim 31 is objected to because of the following informalities: Aa comma should be added following “MT2A”. Appropriate correction is required.
Claim 37 is is objected to because of the following informalities: At line 1, there is an “_” that should be deleted. At line 3, “conditioned from a tumor” should read “conditioned by a tumor”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 22-32,35-40 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 22 remains unclear but it is noted that it has been amended to recite active method steps. The claim now recites that mononuclear phagocytes are incubated but macrophages are obtained. It is not clear if this is intentional as phagocytes are a class of cell types that comprises more than just macrophages. Claim 32 refers to the mononuclear phagocyte of claim 28 with claim 28 being drawn to THEMs (macrophages) made by the method of claim 22. Claims 23-28,32,35-38 are also unclear based on their dependency from claim 22 or intervening dependent claims.
Claim 27 remains unclear. Previously, the claim used the term “consists of” which potentially indicated a Markush was intended. So there is that possibility. But also, the claim now reads “where the culture medium comprises a cell culture medium…” It is not clear if the culture medium is intended to optionally be something other than cell culture medium. As well, the generic “cell culture medium” is followed by specific cell culture mediums, some, but not all, of which are separated by “and / or”. Thus, the claim reads on a combination of specific cell culture mediums. Thus, claim 27 read on a culture medium comprising cell culture medium and RPMI and IMDM. It is not clear if the “cell culture medium” is any cell culture medium and it is not clear of, perhaps, Applicant intended the claim to read more like, “wherein the culture medium comprises a cell culture medium selected from the group consisting of Eagle’s minimal essential medium or derivatives there, Roswell Park Memorial Institute (RPMI) 1640, Media 199, Fischer’s medium and Iscove’s Modified Dulbecco’s Medium (IMDM) and 1-99% medium condition from the tumor (CTM), or tumor supernatant.” The underlined terms are considered a Markush and the 1-99% CTM would be an additive to the specific culture medium. It is also not clear if CTM and tumor supernatant are the same thing. It remains unclear if Applicant also intends to claim combinations of different basal media by use of the term “and/or” as this is not common practice.
Claim 30-31 remains unclear. They are drawn to “The mononuclear phagocyte of claim 29 but claim 29 is limited to a macrophage which is a specific cell type of the class of phagocytes. Phagocytes are any type of cell that phagocytoses. An embodiment of claim 31 reads as “The mononuclear monocyte of claim 29 when claim 29 is limited to a macrophage.
Claim 39 is unclear because it refers to the method according to claim 28. However, claim 28 is drawn to a product.
Claim 40 is unclear because it limits the phagocyte of claim 29 to a macrophage but claim 49 is already limited to a macrophage. It is also recommended that claim 40 use a “wherein” clause.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 40 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 40 is drawn to the macrophage of claim 29, which is drawn to a macrophage. No further limitation is added. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 rejection of claim(s) 22-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lawrence (WO2020169472; IDS) OR Ge (Front. Biol. 2012, 7(4): 359–367) in view of Ke (ONCOLOGY LETTERS 18: 5871-5878, 2019) and Setten (2018, IDS) as evidenced by Zhang (Discover Oncology (2025) 16:1464, 19 pages) is withdrawn in light of the unexpected results as supported by the Locati declaration dated 03/18/2026. The combination of the invitro culture condition of tumor conditioned media and hypoxia led to a different gene expression profile compared to in vivo counterparts (tumor associated macrophages) that was not expected.
Claim Rejections - 35 USC § 102
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)(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.
Claim(s) 29-31 and 35 remain and claim 40 is rejected under 35 U.S.C. 102a1 as being anticipated by Ge (Front. Biol. 2012, 7(4): 359–367 DOI 10.1007/s11515-012-1237-8). The rejection with regard to claim 28 and 32 is withdrawn as the Locati declaration supports that the process of claim 22 used in making the cells of claim 28 (including hypoxia), result in cells that are different from other tumor associated macrophages. The rejection is moot with regard to claims 33 and 34 as they have been canceled.
Claim 29 is drawn to a macrophage that expresses MT2A. Other recited marker genes are optional. With regard to claims 29 and 32, Ge taught a population of M2 macrophages. Ge taught culturing the macrophages in melanoma conditioned media that led to increased expression of MT2A (see page 361, right col., para 1) which is required by claim 29. M2 macrophages do not express TIGAR. Ge taught the macrophages in culture media as well as wash buffer which are considered pharmaceutically acceptable (claim 35).
Applicant’s arguments regarding hypozia and its effects on the cells is not applicable to claims 29-31,35 or 40.
Claim(s) 22-26,28,32 and 35 remain and claims 36-37,39-40 are rejected under 35 U.S.C. 102a1 and a2 as being anticipated by WO2013/110817 (Mazzone) as evidenced by (Trutman, Int. J. Cancer: 77, 378–385,1998; newly added for new claim 36).
Mazzone taught culture of peripheral blood (biological sample, claim 23) monocytes (PBM) in HCT-conditioned media for 18 hours (claim 24), which is media conditioned through the culture of a tumor cell line (HCT116; claim 26,37). Mazzone taught culture under normoxic and hypoxic conditions (see section 5.2, page 63). With regard to claim 28, the resultant macrophage (claim 25) cells expressed CXCR4 and SLC2A3 (see page 7, page 37). With regard to claim 35, pharmaceutically acceptable carriers are discussed at page 30. With regard to newly added claim 36, Mazzone used HCT116 conditioned media and Trutmann evidences that HCT116 cells secrete M-CSF. With regard to claim 39, expression of MT2A is inherent, as all of the method steps to make the cells as required by the claims, are met by Mazzone and it was that tumor associated macrophages express MT2A.
Applicant argues that the cells of the invention have a unique gene expression pattern. This argument is not persuasive as there are no marker expression requirements claimed that are explicitly not met by Mazzone. Further, the method of claim 22 is carried out by Mazzone, which would inherently result in cells with the claimed marker characteristics, as supported by the specification. The method requires culture of mononuclear phagocytes, which include the monocytes of Mazzone, from a biological sample, which is blood in Mazzone, incubating the under hypoxic conditions in a culture medium comprising factors released by tumor cell lines (HCT116 cell conditioned media of Mazzone).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
The rejection of claims 28-35 under 35 U.S.C. 101 is withdrawn. The Locati Declaration dated 03/18/2026 supports that the claimed cells have a very different expression profile than tumor associated macrophages in vivo/in nature.
Conclusion
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 VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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VALARIE E. BERTOGLIO, Ph.D.
Examiner
Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632