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
The instant application is a national stage entry under 35 USC 371 of PCT/US2022/030109, filed
19 May 2022. Acknowledgment is made of Applicant’s claim for benefit under 35 USC 119(e) to US Provisional Application No. 63190387, filed 19 May 2021.
Election/Restrictions
Applicant’s election without traverse of Group I, encompassing claims 1-3, 7-9, 11-13, 15-21, and 24 in the reply filed on 23 June 2026 is acknowledged. The requirement is still deemed proper and is therefore made FINAL. Accordingly, claims 23 and 26-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Therefore, claims 1-3, 7-9, 11-13, 15-21, 23-24, and 26-27, of record 23 June 2026, are pending. Claims 23 and 26-27 are withdrawn for reading on non-elected inventions. Prosecution on the merits commences for claims 1-3, 7-9, 11-13, 15-21, and 24.
Drawings
The drawings filed 17 November 2023 are objected to for containing colored drawings in the
DRW.SUPP file – particularly Figures 1D, 5A, and 5D – without a granted petition for colored drawings.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because there are sequence identifiers within Paragraphs [0048] and [00108]-[00109] of the instant disclosure. More specifically, there is a sequence identifier for a retroviral vector (SEQ ID NO: 872) in Paragraph [0048], an enumerated N-terminal CD8a signal peptide (SEQ ID NO: 1) in Paragraph [00108], and an enumerated single guide-RNA sequence (SEQ ID NO: 2) in Paragraph [00109] of the instant Specification filed 17 November 2023.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Specification
The preliminary amendments to the Specification filed 17 November 2023 are acknowledged and entered into the application file.
However, the disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in at least Paragraph [0046]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The instant Specification is also objected to for referencing colors within the figures, when the referenced figures have not been submitted in color. More specifically, the Specification references colors at least within Paragraph [0010] in reference to Figure 2A. Applicant is requested to review the Specification to identify any additional references to colors within the drawings and delete as appropriate since only black and white drawings are currently accepted. The Specification must be amended to delete reference to specific colors within the text of the Specification.
Appropriate correction is required.
Claim Objections
Claims 1, 12-13, and 21 are objected to because of the following informalities:
Regarding claim 1: The instant claim is objected to for reciting “introducing a vector comprising a CAR into GMPs to form GMPs that express CAR (CAR-GMPs)” instead of “introducing a vector comprising a CAR into GMPs to form GMPs that express the CAR (CAR-GMPs)”, or the like. Likewise, the instant claim is further objected to for reciting “wherein the granulocytes, macrophages or dendritic cells express CAR” instead of “wherein the granulocytes, macrophages or dendritic cells express the CAR”, or the like.
Appropriate correction is required.
Regarding claims 12-13: The instant claims are each objected to for reciting “Neural Basal Medium” instead of “ neural basal medium”, as the neural basal medium is a common noun and should not be capitalized.
Appropriate correction is required.
Regarding claim 21: The instant claim is objected to for reciting “[t]he method of claim 1, wherein the CAR-GMPs are induced to differentiate into macrophages comprising: culturing the CAR-GMPs with a macrophage differentiation medium…” instead of “[t]he method of claim 1, wherein the population of CAR-GMPs are induced to differentiate into macrophages comprising: culturing the population of CAR-GMPs with a macrophage differentiation medium…”, or the like. This is required to better align with the method steps outlined in parent claim 1.
Appropriate correction is required.
Claim Interpretation
Regarding instant claims 12-13, the Examiner is interpreting the recitation of “neural basal medium” to indicate a generic neural basal medium and not the trademarked Neurobasal™ Medium, as the recitation does not exactly match the trademarked name.
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 21 and 24 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.
Regarding claim 21: The instant claim recites the limitation “wherein the macrophages express a CAR”. The scope of the claim is indefinite, as it is unclear if Applicant is requiring the macrophages to express the same CAR as the CAR-GMPs – as is suggested in parent claim 1 and Paragraphs [00113]-[00115] of the instant disclosure – or rather any CAR due to the recitation of “a CAR” in the instant claim.
Appropriate correction is required.
For the sake of compact prosecution, the Examiner will be interpreting the claim as requiring the macrophages to express the same CAR as the CAR-GMPs.
Regarding claim 24: The instant claim is directed to “[t]he method of claim 1, further comprising differentiating the CAR-GMPs into granulocytes comprising: culturing the GMPs with a granulocyte differentiation medium comprising granulocyte colony-stimulating factor (GCSF), wherein the granulocytes express a CAR”. The scope of the claim is indefinite, as it is unclear whether Applicant is further limiting the differentiation step of the population of CAR-GMPs in parent claim 1, or is instead requiring an additional method step wherein the un-engineered and unexpanded GMPs are differentiated into granulocytes that are then engineered to express a CAR. Furthermore, it is unclear if Applicant is requiring the granulocytes to express the same CAR as the CAR-GMPs – as is suggested in parent claim 1 and Paragraphs [00113]-[00115] of the instant disclosure – or rather any CAR due to the recitation of “wherein the granulocytes express a CAR” in the instant claim. Therefore, the ordinary artisan cannot readily determine the metes and bounds of the instant claim, thus rendering the scope of the claim indefinite.
Appropriate correction is required.
For the sake of compact prosecution, the Examiner will be interpreting the claim as further limiting the differentiation step in parent claim 1, wherein the population of CAR-GMPs are cultured with a granulocyte differentiation medium comprising GCSF, and wherein the granulocytes express the same CAR as the CAR-GMPs.
Claim Rejections - 35 USC § 103
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 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.
Claims 1-3, 7-9, 11-13, 15-21, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Ying et al (WO 2020/076739 A1, of record on IDS filed 17 November 2023) in view of O’Neill (WO 2019/135879 A1, of record on IDS filed 30 April 2025).
Ying et al is considered prior art under 35 USC 102(a)(1), with a publication date of 16 April 2020. It is of note that this is greater than one year prior to the effective filing date of the instant invention. O’Neill is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claim 1: Ying et al disclose methods for the long-term expansion of granulocyte-macrophage progenitors (GMPs), the GMPs generated therefrom, and uses of the GMPs thereof (Abstract; Paragraph [0004]).
As such, Ying et al disclose the expansion and culturing of the GMPs in a defined culture medium to generate a population of GMPs, and then inducing the population of GMPs to differentiate into granulocytes or macrophages in vitro (Paragraphs [0005]-[0010], [0016], [0028], [0031]-[0033], [0041], [0044], [0062], [0067]-[0069]; Figure 2).
Ying et al further disclose that the GMPs can be genetically engineered to form a macrophage that expresses a chimeric antigen receptor (CAR) (Paragraphs [0006], [0028], [0053]).
Ying et al do not disclose that the GMPs are engineered to express a CAR via the introduction of a vector comprising the CAR into the GMPs, as required by instant claim 1.
O’Neill, however, discloses macrophage precursor cells that lack functional expression of MHC genes and are engineered to comprise a CAR (Abstract). O’Neill further discloses that the macrophage precursor cells are engineered via the transduction of a vector comprising the CAR and can be further differentiated into macrophages, wherein the macrophage maintains expression of the CAR (Paragraphs [00100], [00251]-[00253], [00260]). It is of note that O’Neill defines “macrophage precursor cell” as any cell in the developmental lineage of macrophages that can be differentiated to produce a macrophage (Paragraph [0089]).
Therefore, it would have been prima facie obvious to have modified the method of Ying et al such that the GMPs are transduced with a vector comprising a CAR, as detailed in O’Neill. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to introduce the CAR into the GMP, as macrophage precursor cells are more long-lived compared to macrophages and easier to transduce before being terminally differentiated (O’Neill: Paragraphs [00100], [00260]). Furthermore, the ordinary artisan would have had a reasonable expectation of success given that the disclosure of Ying et al reasonably suggests the maintenance and engineering of the GMPs to form CAR-macrophages, while the disclosure of O’Neill provides the necessary protocols to engineer the GMPs to express a CAR. See MPEP § 2143(I)(G).
Consequently, Ying et al as modified by O’Neill render obvious a method of genetically engineering GMPs to express a CAR, wherein the GMPs are transduced with a vector comprising the CAR, expanded and cultured in a defined culture medium, and then induced to differentiate into CAR-macrophages in vitro. As the GMP-derived macrophage maintains expression of the CAR, this therefore renders obvious the method of the instant claim.
Regarding claims 2-3: Following the discussion of claim 1, Ying et al further disclose that the GMPs are obtained from hematopoietic stem cells (claim 3) (Paragraphs [0005], [0037], [0039]). This therefore reads on the method of instant claim 2.
Regarding claim 7: Following the discussion of claim 1, O’Neill further discloses that the CAR comprises an antigen-binding extracellular domain, a transmembrane domain, and a cytoplasmic domain that polarizes a macrophage into a M1 macrophage – which allows for the treatment of cancer via an upregulation of the immune system and secretion of proinflammatory cytokines (Paragraphs [0006], [0011], [0014], [0033], [00102]-[00109], [00113], [00133], [00241]-[00255]). This therefore renders obvious the method of the instant claim for the same reasons as discussed in the rejection of instant claim 1.
Regarding claims 8-9: Following the discussion of claim 1, O’Neill further discloses that the CAR is introduced into the macrophage precursor via a lentiviral vector (claims 8-9) (Paragraphs [00112], [00115], [00161], [00184]-[00192], [00196]-[00199], [00242], [00251]-[00253]). This therefore renders obvious the method of the instant claims for the same reasons as discussed in the rejection of instant claim 1.
Regarding claim 11: Following the discussion of claim 1, Ying et al further disclose that the GMPs are cultured in a culture medium comprising: (i) a growth factor, (ii) a B-Raf kinase inhibitor, and (iii) a Wnt activator and/or a GSK-3 inhibitor, wherein the GMPs remain substantially morphologically unchanged after undergoing multiple cell passages and/or clonal expansion (Paragraphs [0005], [0031], [0041], [0045]). This therefore reads on the method of the instant claim.
Regarding claims 12-13: Following the discussion of claim 11, Ying et al further disclose that the culture medium comprises DMEM/F12 and neural basal medium (claim 12) at a ratio of about 5:1 to about 1:5 (Paragraphs [0005], [0041], [0065]). This therefore reads on the method of instant claim 13.
Regarding claims 15-16: following the discussion of claim 11, Ying et al further disclose that the culture medium is supplemented with insulin, transferrin, bovine serum albumin, fraction V, putrescine, sodium selenite, DL-a tocopherol, and linolenic acid (Paragraphs [0005], [0042], [0065]). This therefore reads on the method of instant claims 15-16.
Regarding claim 17: Following the discussion of claim 11, Ying et al further disclose that the growth factor is stem cell factor (Paragraphs [0005], [0014], [0030]-[0031], [0041], [0045]-[0046], [0050], [0064]). This therefore reads on the method of the instant claim.
Regarding claim 18: Following the discussion of claim 11, Ying et al further disclose that the B-raf kinase inhibitor is GDC-0879 (Paragraphs [0005], [0014], [0030]-[0031], [0041], [0045], [0047], [0064]). This therefore reads on the method of the instant claim.
Regarding claim 19: Following the discussion of claim 11, Ying et al further disclose that the Wnt activator is SKL 2001 (Paragraphs [0005], [0014], [0030]-[0031], [0041], [0045], [0051], [0064]). This therefore reads on the method of the instant claim.
Regarding claim 20: Following the discussion of claim 11, Ying et al further disclose that the GSK-3 inhibitor is CHIR99021 (Paragraphs [0005], [0030]-[0031], [0041], [0045], [0052], [0065]). This therefore reads on the method of the instant claim.
Regarding claim 21: Following the discussion of claim 1, Ying et al further disclose that the GMPs are differentiated into macrophages via the culture of the GMPs in macrophage differentiation medium comprising macrophage colony-stimulating factor (Paragraphs [0006], [0016], [0020], [0028], [0049], [0062], [0067]). As the final macrophages will express the same CAR as the GMPs – as is taught in the rejection of claim 1 – this therefore reads on the method of the instant claim.
Regarding claim 24: Following the discussion of claim 1, Ying et al further disclose that the GMPs are differentiated into granulocytes via the culture of the GMPs in granulocyte differentiation medium comprising granulocyte colony-stimulating factor (Paragraphs [0006], [0048], [0062], [0069]). As the final granulocytes will express the same CAR as the GMPs – as is reasonably suggested in the rejection of claim 1 along with the fact that GMPs serve as precursor cells to macrophages and granulocytes – this therefore reads on the method of the instant claim.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALYSSA G WESTON/Examiner, Art Unit 1633
Prosecution Insights