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 .
DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of CD3+ T cells as the T cells, a combination of anti-CD3 antibody and an anti-CD28 antibody as the T cell activating and T cell co-stimulatory molecules, CD8 as the cell surface marker, CCL19 as the recruitment compound and blood as the biological sample, in the reply filed on 21 Aug 2025 to the species election requirement is acknowledged.
Claims 97, 98, 103 and 112 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. These claims require alternative species to those elected.
Claims 96, 99-102, 104-111 and 113-124 are under consideration to the extent of the elected species, i.e., CD3+ T cells as the T cells, a combination of anti-CD3 antibody and an anti-CD28 antibody as the T cell activating and T cell co-stimulatory molecules, CD8 as the cell surface marker, CCL19 as the recruitment compound and blood as the biological sample.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 18 July 2023, 02 Nov 2023, 12 Jul 2024, 21 Aug 2025, is in compliance with the provisions of 37 CFR 1.97, except where noted. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities:
The specification references colors in the drawings, however, the drawings are in black and white and the colors cannot be discerned. For example, page 106 lines 16-17 refers to the lipids as green but there is no green in the figure. The same issue is present in the description of figures 11 (page 109 line 21), figure 20 (page 112 lines 35-36), figure 19 (page 21 lines 3 and 5), figure 28 (page 23 line 3), figure 29 (page 23 line 19), figure 39 (page 27 line 19).
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 100 and 102 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 100 recites the limitation "the cell surface markers". There is insufficient antecedent basis for this limitation in the claim. Base claim 99 recites “one or more cell-surface markers”, which encompasses multiple cell-surface markes, and it is unclear whether “the cell surface marker” includes just one or more than one cell-surface marker. Amending claim 100 to recite “the one or more cell-surface markers” would overcome this rejection.
Claim 102 is unclear in the recitation of “the T cells.” There are two types of T cells in the instant claims, namely T cells in the sample and the manipulated T cells (for example, see claims 97 and 99). It is unclear which T cells are referred to in claim 102.
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.
Claims 96, 99-102, 104-109, 111, 113-124 are rejected under 35 U.S.C. 103 as being unpatentable over Stephan et al. (Nature biotechnology, Vol 33 No 1 Jan 2015, listed on IDS filed 18 Jul 2023) in view of Kim et al. (US 2015/0072009, published 12 Mar 2015, listed on IDS filed 18 Jul 2023), Jaeyun Kim et al. (Nature biotechnology, Vol 33 No 1 Jan 2015, referred to below as Jaeyun, listed on IDS filed 18 Jul 2023) and Trautmann et al. (Immunology 2003, 108, 305-312) as evidenced by the instant specification and evidenced by Williams et al. (Journal of Clinical Oncology, Volume 42, Issue 29, pages 3430-3422).
Stephan teaches biopolymer implants that enhance the efficacy of adoptive T-cell therapy (title). Stephan teaches macroporous scaffolds from polymerized alginate that incorporate porous silica microparticles and are coated with lipid bilayers to mimic cell membranes (page 97 right column). A coated lipid bilayer mimicking cell membranes is understood to render obvious the fluid supported lipid bilayer and the cell mimetic scaffold of claim 96. Stephan teaches that T cells migrate through the scaffolds (page 97 right column) and the polymer acts as an active reservoir from which the propagating cells are released as the material biodegrades (page 97 left column) and cells infusing into the scaffold matrices (page 103 left column) and Stephan provides an image where the T cells are loaded into pores in a scaffold (Fig 1b), thereby rendering obvious contacting the scaffold with a biological sample and permitting T cell infiltration as in claim 96. Stephan teaches coupling anti-CD3, anti-CD28 and anti-CD137 antibodies to the microsphere bilayers (page 98 left column) and antibody conjugation to lipid-coated microparticles (page 102 right column), rendering obvious functional molecules presented on the SLB as in claim 96. As evidenced by the instant specification, antibodies binding to CD3/CD28 are T-cell activating and co-stimulatory molecules (page 56 lines 3-6), and thus the coupled anti-CD3 and anti-CD28 antibodies render obvious the activating and co-stimulatory molecules of claims 96, 108 and 109. Stephen teaches that adding particles with these stimulants triggered a 22 fold boost in T-cell proliferation (page 98 left column), rendering obvious a “method for the manipulation of T cells” as in claim 96 and expansion as in claim 124. Stephen teaches preparing T cells from splenocytes (page 102 right column). Regarding the contacting ex vivo as in claim 101, Stephan teaches ex vivo prestimulation of T cells (page 102 right column). Stephan teaches the isolation of CD8+ t cells and the preparation of effector CD8+ T cells (page 102 Preparation of tumor-targeting lymphocytes), rendering obvious the T cells of claims 102, 104 and 105. As evidenced by Williams, CD3 is the universal marker for T cells (page 3431 left column) and thus the CD8 t cells taught by Stephan are also CD3+ T cells (the elected species of T cell). Stephan teaches that the microparticles harbor interleukin 15 superagonist (page 97 right column – page 98), rendering obvious claims 106 and 107, as interleukins are homeostatic agents as evidenced by the instant specification (page 106 line 5). Stephan teaches that biomaterials are known for supplying antigens (page 100 right column), rendering obvious claim 113. Stephen teaches adding 2.5 mg of lipid to 120 μL of a 100 mg/mL suspension spherical silica (page 102 Preparation of stimulatory lipid-coated silica microspheres). The total silica in 120 μL of a 100 mg/mL suspension is 12 mg which results in a ratio of 1:4.8 lipid to silica (2.5mg:12mg) rendering obvious instant claim 122.
Stephan does not teach mesoporous silica rods and their dimensions as in the instant claims, detecting cell surface markers, the biological sample is blood (the elected species) or a recruitment compound. These deficiencies are made up for in the teachings of Kim and Jaeyun.
Kim teaches a composition comprising mesoporous silica rods comprising an immune cell recruitment compound and an immune cell activation compound that achieve robust recruitment of cells (abstract, [0004]). Kim teaches that the rods have a length from 50 to 250 μm ([0004]), rendering obvious the lengths of claims 116-119. Kim teaches that the rods generate a 3D space that allows for cell infiltration ([0016]). Kim provides SEM images of the silica rods and the scale bars for the images indicate the spaces between the rods is on the order of approximately 10 μm (Fig 14A), rendering obvious claim 115. Kim teaches that teh system induces teh clonal expansion of CD4 and CD8 T cells ([0040]). Kim teaches an example where 5 mg/mouse of the silica rods were loaded with 100 μg CpG-ODN ([0021]) which is a ratio of 50:1, indicating this ratio of rod to agent as suitable for the system and rendering obvious claim 115. Kim teaches exemplary immune cell recruitment compounds such as chemokine ligand 19 ([0005]). Kim teaches staining for CD8 ([0024]) rendering obvious detecting cell surface markers such as CD8 as in claims 99 and 100.
Jaeyun teaches high aspect ratio mesoporous silica rods that form microporous structures that provide a 3D cellular microenvironment for host immune cells and enhance systemic helper T cells (abstract). Jaeyun teaches that interparticle pores bigger than the size of cells allow for cells to infiltrate that space (page 64 right column). Jaeyun teaches that the mesoporous silica rods have an average length of 88 μm and a 4.5 μm diameter (page 64 right column). A length of 88 μm and a 4.5 μm diameter is an aspect ratio of 20, as in instant claim 121.
Trautmann teaches that a variety of T cells, such as cytotoxic CD8 T cells, are present in blood (summary, page 311, entire document).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have used mesoporous silica rods in the implants of Stephen and to detect cell markers for CD8 and include recruitment compounds such as chemokine ligand 19 and to have the biological sample as blood. Biopolymer implants with porous silica microparticles coated with lipid bilayers and that incorporate T cells and proliferate T cells is known by Stephen. Mesoporous silica rods are also used with T cell infiltration, as known from Kim and Jaeyun. The use of mesoporous silica rods for the silica microparticles in the method of Stephen is a simple substitution that one would expect to provide suitable stimulation and infiltration for T cells. Detecting CD8 surface markers and incorporating chemokine ligand 19 recruitment compounds may be used with silica rods with T cell manipulation, as known from Kim and Jaeyun, indicating these are standard processes with T cell manipulation. Additionally, Stephan indicates use of the method with splenic samples but T cells are also present in blood samples, as known from Trautmann, and one would recognize blood as an alternative biological sample for recruiting T cells for manipulation and proliferation.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Claim 110 is rejected under 35 U.S.C. 103 as being unpatentable over Stephan et al. (Nature biotechnology, Vol 33 No 1 Jan 2015, listed on IDS filed 18 Jul 2023) in view of Kim et al. (US 2015/0072009, published 12 Mar 2015, listed on IDS filed 18 Jul 2023), Jaeyun Kim et al. (Nature biotechnology, Vol 33 No 1 Jan 2015, referred to below as Jaeyun, listed on IDS filed 18 Jul 2023) and Trautmann et al. (Immunology 2003, 108, 305-312) as evidenced by the instant specification and evidenced by Williams et al. (Journal of Clinical Oncology, Volume 42, Issue 29, pages 3430-3422) as applied to claims 96, 99-102, 104-109, 111, 113-124 above and further in view of Platscher et al. (US 2015/0030669, published 29 Jan 2015, listed on IDS filed 18 Jul 2023) and Trinath et al. (Blood, 22 Aug 2013, Vol 122, No 8).
The teachings of Stephan, Kim, Jaeyun and Trautmann are described supra. Stephan, Kim, Jaeyun and Trautmann do not teach immunoglobulin binding to an FC-fusion protein. This deficiency is made up for in the teachings of Platscher and Trinath.
Platscher teaches carrier systems comprising ether-lipids conjugated to bioactive ligands for use in targeted delivery and/or antigen display systems ([0001], [0009]). Platscher teaches a nanoparticulate carrier system in the form of a lipid-coated particle coated with a lipid-ligand conjugate ([0011]). Platscher teaches the carrier system may be a microparticulate or nanoparticulate material in various shapes and forms such as rods ([0022]). Platscher teaches the antigen presenting system includes a T-cell antigen receptor on the surface of a T cell ([0036]). Platscher teaches ligands such as the Fc region of immunoglobulins ([0026]).
Trinath teaches that immunoglobulins are delivered as spart of therapeutic preparations and are known to expand regulatory T cells (title, abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have incorporated immunoglobulins with FC region in the scaffolds. Immunoglobulins provide therapeutic benefits and expand regulatory T cells, as known from Trinath, and the Fc region of immunoglobulins may be incorporated onto lipid-ligand conjugate carrier systems, as known from Platscher. The incorporation of the immunoglobulin thus represents the addition of a known component that will assist in the T cell therapy associated with the scaffold.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EDWIN C MITCHELL whose telephone number is (571)272-7007. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/E.C.M./Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600