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 1-20 are currently pending and under consideration.
Specification
The disclosure is objected to because of the following informalities: Paragraph 0120 states “In some embodiments, the first and second fusion proteins are SEQ ID NO: 1 and SEQ ID NO: 2, respectively.” However, the sequence listing as filed indicates that SEQ ID NO:2 is a DNA sequence.
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.
Claim 17 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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. Evidence that claim 17 fail(s) to correspond in scope with that which the inventor or a joint inventor, or for pre-AIA applications the applicant regards as the invention can be found in the reply filed 01-19-2024. In that paper (sequence listing XML file), the inventor or a joint inventor, or for pre-AIA applications the applicant has submitted that SEQ ID NO:2 is a DNA construct, and this statement indicates that the invention is different from what is defined in the claim(s) because SEQ ID NO:2 is defined in the claims as an amino acid sequence.
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 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.
Claim(s) 1-6, 11-14, 16, and 18-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al. (WO 2019/027847, published February 2019).
A reasonable interpretation of claim 1 is that formula A-B-C and formula D-E-F “comprise” bispecific antibodies in any order. Thus, D-E-F could be D-F-E. Further, an “antibody moiety” is equivalent to a “protein binding moiety”.
As to claim 1, Zhang et al. teach engineered extracellular vesicles [0005] comprising fusion proteins [0016] of A-B-C or D-E-F or D-F-E where A and B are first and second antibody moieties and D and F are protein binding moieties. All such moieties are connected to an exosomal membrane protein [0101] (the C or E part of the fusion) such that they are displayed on the surface of the engineered extracellular vesicle. Further, Zhang et al. teach [0007-0008] that the first antibody moiety (or protein binding moiety) binds to a first immune cell marker protein and the second antibody moiety (or protein binding moiety) binds to cancer cell surface-marker protein. Zhang et al. also refers to these engineered vesicles as “bispecific exosomes”. See Figures 1 and 3.
As to claim 2, Zhang et al. teach [0005] that the extracellular vesicle comprises an exosome, a liposome, a microvesicle or an apoptotic body.
As to claims 3, 13-14, Zhang et al. teaches [0006, 0103, 0155] that the first and second antibody moiety are a single chain variable fragment (scFv), a single domain antibody, a bispecific antibody, or a multi-specific antibody. Zhang et al. teach that the scFv can target CD3 and a tumor-associated antigen [Fig 3] such as EGFR. See Figure 15.
As to claim 4, Zhang et al. teach [0155, 0128, claim 13, 0157] that the fusion proteins can target immune cell surface markers such as CD3 and CD16 and that these antigen targets or surface-marker proteins do not have to be same. Also see Figure 3 and Fig.4A, the bispecific antibodies can target CD3 or CD16.
As to claims 5-6, Zhang et al. teach [0006, 0128, 0157] that the fusion proteins also target cancer cell surface markers (e.g., EGFR, HER2) where the first and second cancer surface markers don’t have to be the same. Also see [0019] and Fig. 4A.
As to claim 11, Zhang et al. teach [0025, claim 55, 0101] that the exosomal membrane proteins can be derived from Platelet Derived Growth Factor Receptor or CD9.
As to claims 12 and 16, Zhang et al. teach that the fusion proteins can comprise one or more epitope tags [0123] or linkers [0119]. For example, Zhang et al. teach an engineered hemagglutinin (HA) tag-anti-cluster of differentiation 3 (CD3)/epidermal growth factor receptor (EGFR) single chain antibody (scFv)-GGGGS linker- myc tag-platelet derived growth factor receptor beta (PDGFRB) transmembrane domain fusion protein sequence, useful for treating cancer. See SEQ ID NO:1 of Zhang in 1.rag file. This corresponds to T1-A-L1-B-L2-T2-C or T3-D-L3-F-L4-E.
As to claim 18, Zhang et al. teach [0153] that the engineered extracellular vesicle has a particle size of about 25 nm to about 150nm.
As to claim 19, Zhang et al. teach [0224] compositions of the engineered vesicles with pharmaceutically acceptable carriers.
As to claim 20, Zhang et al. teach [FIG. 34A-34C] methods of treating triple negative breast cancer comprising administering to a subject bispecific exosomes targeting CD3 and EGFR.
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.
Claim(s) 7-10, and 15 are further rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2019/027847, published February 2019) in combination with the teachings of Schreiber et al. (US 2020/0261537, September 30, 2016, IDS).
Zhang et al. teach as set forth above and further teach [0103] that the term "antigen binding domain" refers to any protein or polypeptide domain that can specifically bind to an antigen target or cell surface receptor. Non-limiting examples include an antibody, an antibody fragment, a single domain antibody, a bispecific antibody, a fragment of a bispecific antibody, an scFv antibody fragment, a heavy chain variable domain (VH), a light chain variable domain (VL). Also intended within the scope of this disclosure are biological equivalents of the exemplified polypeptide and polynucleotide sequences.
Regarding Claim 7, Zhang et al. does not teach that the first binding moiety is a type I membrane protein and the second binding moiety is a type II membrane protein. Regarding claims 8 and 15, Zhang et al. does not teach wherein the type I membrane protein (or a first protein binding moiety) is PD-1 and the type II membrane protein (or second protein binding moiety) is OX40L. Zhang does not teach wherein the type I membrane protein is LAG3, TIM-3, KIR, CD96, etc. (Claim 9) or wherein the type II membrane protein is 4-1BBL, CD70, GITRL, CD40L, etc. (Claim 10).
Schreiber et al. teach [0008] similar engineered vesicles to treat cancer comprising an immune inhibitory receptor extracellular domain (e.g. a first protein binding moiety) and an immune stimulatory ligand extracellular domain (e.g., a second protein binding moiety) which can, without limitation, deliver an immune stimulation to a T cell while masking a tumor cell's immune inhibitory signals. These extracellular domains can be of Type I and Type II membrane proteins. For example, a chimeric protein construct comprising (i) the extracellular domain of PD-1 and (ii) extracellular domain of OX40L, allows for the disruption of an inhibitory PD-L1/L2 signal and its replacement with a stimulating OX40L. These constructs can be assembled in liposomes or microparticles [0162, 0169] and engineered as type I and type II [0036-0041] membrane proteins. See Figures 1 and 3. Further, these constructs can be used to treat cancer [0163]. The Type I and Type II membrane proteins are also not limited to PD-1 and OX40L respectively. Schreiber et al. teach [0041, 0046] that the present chimeric proteins can comprise an extracellular domain of a human type I transmembrane protein such as TIM-3, BTLA, PD-1, CTLA-4, CD244, CD160, TIGIT, SIRPα/CD172a, 2B4, VISTA, VSIG8, LAG3, CD200 and TMIGD2. In relation to Type II transmembrane proteins, the reference further teaches [0007] that the chimeric protein of the present invention comprises an extracellular domain of an immune stimulatory signal which can specifically include OX-40 ligand, LIGHT (CD258), GITR ligand, CD70, CD30 ligand, CD40 ligand, CD137 ligand, TRAIL and TL1A.
One of ordinary skill in the art at the time of filing would consider it prima facie obvious to modify the teachings of Zhang et al. to include the Type I and Type II membrane binding proteins of Schreiber et al. because Zhang already taught methods of treating cancer using engineered extracellular vesicles comprising antibody or protein-binding moieties that targeted similar surface molecules on immune cells and cancer cells. For example, both Zhang and Schreiber taught using liposomes and/or microvesicles that target cell surface expression of PD-1 ligands and CD40L. (See claim 49 of Zhang et al. and claim 49 of Schreiber et al.). While Zhang et al. mostly taught antigen binding domains that used antibody-like structures and Schreiber et al. taught Type I and Type II membrane proteins with antigen binding domains, the goal was similar- to target tumor cell surface marker and immune cell surface markers. Further, one would have been motivated to incorporate the Type I and Type II membrane proteins of Schreiber et al. because Schreiber et al. taught that use of an immune inhibitory receptor extracellular domain together with an immune stimulatory ligand extracellular domain can, without limitation, deliver an immune stimulation to a T cell while masking a tumor cell's immune inhibitory signals. Thus, the masking of negative immune signals and stimulation of positive immune signals in a single construct would be advantageous for treating cancer. Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions to yield stable liposome formulations as 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 1-6, 11-16, and 18-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11938219. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are broadly overlapping in scope and are not patentably distinct.
Claims 1 and 8 of US Patent 11938219 are drawn to:
An isolated engineered extracellular vesicle comprising a first antigen binding domain that comprises an anti-EGFR scFv antibody fragment and a second antigen binding domain that comprises an anti-CD3 scFv antibody fragment and, the first and second antigen binding domains being fused to one or more extracellular vesicle addressing domains expressed on the surface of the vesicle, wherein the one or more extracellular vesicle addressing domain comprises platelet-derived growth factor receptor (PDGFR) transmembrane domain.
A fusion polypeptide comprising: a first antigen binding domain that comprises an anti-EGFR scFv antibody fragment and a second antigen binding domain that comprises an anti-CD3 scFv antibody fragment, a linker polypeptide, and an exosome addressing domain and an exosome addressing domain that comprises platelet-derived growth factor receptor (PDGFR) transmembrane domain
This is broadly anticipated (or rendered obvious) by currently pending claim 1 drawn to engineered extracellular vesicles comprising first and second fusion proteins which can bind to immune cell surface-marker proteins such as EGFR and cancerous cell surface markers such as CD3. The first (A-B-C) and second (D-E-F) fusion proteins can be duplicate bispecific proteins as one reasonable interpretation of pending claim 1 is that formula A-B-C and formula D-E-F “comprise” bispecific antibodies in any order. Thus, D-E-F could be D-F-E. Further, an “antibody moiety” is equivalent to a “protein binding moiety”. Alternatively, one of ordinary skill in the art at the time of filing would consider it obvious to incorporate multiple bispecific fusion proteins that recognize different antigens to accommodate for tumor cell heterogeneity thus increasing the probability of a successful response to treating a tumor. In relation to claim 8, pending claim 16 includes the linkers. Regarding the patented term “one or more extracellular vesicle addressing domains”, while these are inclusive of at least PDGFR, they also comprise other extracellular vesicle addressing domains such as CD9 as claimed in pending claim 11. The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of the claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.
Pending claims 3 and 13 are inclusive of the single chain variable fragments (scFv) used in patented claims 1 and 8.
Pending claims 4-6, and 14 encompasses targeting CD3- immune cell surface marker proteins and EGFR- cancer cell surface marker proteins used in patented Claims 1 and 8.
Claim 2 of the ‘219 patent is drawn to:
The isolated engineered extracellular vesicle of claim 1, wherein the extracellular vesicle is selected from the group of: an exosome, a liposome, a microvesicle, and an apoptotic body-which is the same as pending claim 2.
Claim 3 of the ‘219 patent is drawn to:
The isolated engineered extracellular vesicle of claim 1, further comprising a purification and/or a detectable label; which is nearly the same or is anticipated by Claim 12 of the pending claims.
Claim 5 of the ‘219 patent is drawn to:
A composition comprising an isolated engineered extracellular vesicle of claim 1 and a carrier which is nearly identical in scope to Claim 19 of the pending claims.
Claim 20 of the pending claims is drawn to treating “triple negative breast cancer” which is a species of the genus of cancers encompassed by patented claims 6-7, and 12-15. The specification of the patent teaches the in vivo efficacy of treating triple negative breast cancer xenograft models (Figs. 34A-34C). The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of the claim. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.
Patented Claims 9-10 are drawn to isolated polynucleotides encoding the fusion proteins and methods of making the fusion proteins which would be obvious to include in the pending claims because one would need the DNA to construct the fusion proteins.
Patented claim 4 is drawn to including a therapeutic agent encapsulated in the vesicle. None of the pending claims include an additional therapeutic agent. However, in terms of treating cancer it is common in the art to include additional known anti-cancer agents to improve the efficacy of treatment.
Regarding pending claim 18, wherein the engineered extracellular vesicle has a particle size of about 25 nm to about 150 nm. These sizes are not claimed in the patent. Again, however, the portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of the claim. Thus, one would look to the specification of the patent to determine what sizes of the vesicles are encompassed by the scope of the claims. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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