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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 7/9/2026 has been entered.
Election/Restrictions
Applicant’s election without traverse of Group III in the reply filed on 8/27/2024 is acknowledged. Claims 1, 20-23, 50, and 51 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group I and II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/27/2024.
New claims 50 and 51 are drawn to Group I and new claim 52 is drawn to Group III.
Status of Claims
Cancelled: 2-19, 24-28, 30, 31, 33-38
New: 50, 51, 52
Withdrawn: 1, 20-23, 50, 51
Examined Herein: 29, 32, 39-49, 52
Priority
Priority to PRO 62/817,657 filed on 3/13/2019 and PCT/US2020/022832 filed on 3/13/2020 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/13/2021 is in compliance with the
provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the
examiner.
Drawings
The drawings filed on 9/13/2021 are accepted.
Claim Objections
Applicant is advised that should claim 32 be found allowable, claim 44 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Withdrawn Rejections
The rejection of claim 44 under 35 USC § 112(b) is hereby withdrawn in view of Applicant’s amendments to claim 44, which depends upon a non-cancelled claim.
The rejection of claims 29, 32, 39-42, and 44-47 under 35 U.S.C. 102(a)(1) over Guldris is hereby withdrawn in view of Applicant’s substantive amendments to claim 29.
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.
Claims 29, 32, and 39-49 are rejected under 35 U.S.C. 103 as being unpatentable over Guldris (Magnetite Nanoparticles for Stem Cell Labeling with High Efficiency and Long-Term in Vivo Tracking, 12/15/2016, Bioconjugate Chemistry, Volume 28, Issue 2), in view of Horak (US 2009/0309597 A1, Published 12/17/2009).
With respect to claim 29, Guldris discloses an imaging composition comprising:
Extracellular vesicles (which are inherently comprised within the mesenchymal stem cells), imaging particles (USPIO);
A therapeutic agent (glucosamine); [Guldris, Page 364, Figure 1]
With respect to claims 32 and 44, Guldris discloses a method of imaging comprising administering the imaging composition to a subject. [Guldris, Page 366, Col. 2, Paragraph 3 and Page 366, Figure 3, Page 367, Col. 1, Paragraph 1]
With respect to claim 39, Guldris discloses that the imaging particles are USPIOs. [Guldris, Page 364, Figure 1] USPIO is magnetic.
With respect to claim 40, Guldris discloses that the imaging particles are USPIOs. [Guldris, Page 364, Figure 1] USPIO is a supermagnetic iron oxide particle.
With respect to claim 41, Guldris discloses that the imaging particles are USPIOs. [Guldris, Page 364, Figure 1] USPIO is a nanoparticle.
With respect to claim 45, Guldris discloses a method of imaging comprising administering the imaging composition to a subject, wherein the imaging particles are USPIOs. [Guldris, Page 366, Col. 2, Paragraph 3 and Page 366, Figure 3, Page 367, Col. 1, Paragraph 1] USPIO is magnetic.
With respect to claim 46, Guldris discloses a method of imaging comprising administering the imaging composition to a subject, wherein the imaging particles are USPIOs. [Guldris, Page 366, Col. 2, Paragraph 3 and Page 366, Figure 3, Page 367, Col. 1, Paragraph 1] USPIO is a supermagnetic iron oxide particle.
With respect to claim 47, Guldris discloses a method of imaging comprising administering the imaging composition to a subject, wherein the imaging particles are USPIOs. [Guldris, Page 366, Col. 2, Paragraph 3 and Page 366, Figure 3, Page 367, Col. 1, Paragraph 1] USPIO is a nanoparticle.
Guldris further discloses that the USPIOs are coated with poly(acrylic acid). [Guldris, Page 367, Col. 1, Paragraph 4]
Guldris does not disclose that the composition comprises sticky elements or that the composition has less than 40 weight% of sticky imaging particles that are not associated with extracellular vesicles, where weight% is based on total composition weight.
However, with respect to claims 29, 32, 42, 43, 48, and 49, Horak discloses that poly(amino acids), including polyhistidine, and synthetic polymers derived from polyacrylic acid are suitable coatings for iron oxide superparamagnetic nanoparticle probes. [Horak, Abstract] Polyhistidine is a peptide having more than amino acid residues and at least two histidine amino acid residues.
Modifying the imaging composition and method disclosed by Guldris by replacing the polyacrylic acid coating on the USPIOs with polyhistidine results in the imaging composition of claims 29, 42, and 43 and the method of claims 32, 48, and 49, wherein the imaging composition comprises:
Extracellular vesicles (exosomes) encapsulating sticky imaging particles comprising:
imaging particles (USPIO) and sticky elements comprising a peptide (polyhistidine) with more than 2 histidine residues;
A therapeutic agent (cisplatin);
wherein, the composition has less than 40 weight % of sticky imaging particles that are not associated with exosomes, as the sticky imaging particles are internalized by the mesenchymal cells comprising exosomes, such that all the sticky imaging particles are associated with extracellular vesicles.
It would be obvious to one of ordinary skill in the art to modify the composition and method disclosed by Guldris by replacing the polyacrylic acid coating on the USPIOs with polyhistidine and have a reasonable expectation of success. Guldris discloses a composition comprising USPIOs coated with poly(acrylic acid). Horak discloses that both polyhistidine and synthetic polymers derived from polyacrylic acid are suitable coatings for iron oxide superparamagnetic nanoparticle probes. Accordingly, the combined teachings of Guldris and Horak reasonably suggest that the iron oxide superparamagnetic nanoparticle in the composition disclosed by Guldris may be alternatively coated with polyhistidine. One would have been motivated to do so because it is prima facie obvious to substitute equivalents known for the same purpose when their equivalency is recognized in the art. MPEP 2144.06. In the present case, Horak discloses polyhistidine, and synthetic polymers derived from polyacrylic acid are suitable coatings for iron oxide superparamagnetic nanoparticle probes. [Horak, Abstract] Therefore, it is prima facie obvious to substitute one known coating for iron oxide superparamagnetic nanoparticles for another.
Claims 29, 32, 39-49, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Acar (US 2021/0023239 A1, Filed 3/10/2018), in view of Jia (NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo, 6/21/2018, Biomaterials, 178, 302e316).
With respect to claim 29, Acar discloses an imaging composition comprising:
Sticky imaging particles comprising:
imaging particles (SPION), and sticky elements comprising a peptide (AGO2) with histidine amino acid residues;
A therapeutic agent, cisplatin. [Acar, Figure 1, 0125]
With respect to claims 32 and 44, Acar discloses a method of imaging comprising administering the imaging composition to a subject. [Acar, 0088]
With respect to claim 39, Acar discloses that the imaging particles are SPIONs. [Acar, Figure 1, 0125] SPION is magnetic.
With respect to claim 40, Acar discloses that the imaging particles are SPIONs. [Acar, Figure 1, 0125] SPION is a supermagnetic iron oxide particle.
With respect to claim 41, Acar discloses that the imaging particles are SPIONs. [Acar, Figure 1, 0125] SPION is a nanoparticle.
With respect to claim 42, Acar discloses that the sticky element is AGO2. [Acar, Figure 1, 0125] AGO2 has more than two amino acid residues.
With respect to claim 43, Acar discloses that the sticky element is AGO2. [Acar, Figure 1, 0125] AGO2 has 16 histidine residues.
With respect to claim 45, Acar discloses a method of imaging comprising administering the imaging composition to a subject, wherein the imaging particles are SPIONs. [Acar, 0088] SPION is magnetic.
With respect to claim 46, Acar discloses a method of imaging comprising administering the imaging composition to a subject, wherein the imaging particles are SPIONs. [Acar, 0088] SPION is a supermagnetic iron oxide particle.
With respect to claim 47, Acar discloses a method of imaging comprising administering the imaging composition to a subject, wherein the imaging particles are SPION. [Acar, 0088] SPION is a nanoparticle.
With respect to claim 48, Acar discloses a method of imaging comprising administering the imaging composition to a subject, wherein the sticky element is AGO2. [Acar, 0088] AGO2 has more than two amino acid residues.
With respect to claim 49, Acar discloses a method of imaging comprising administering the imaging composition to a subject, wherein the sticky element is AGO2. [Acar, 0088] AGO2 has 16 histidine residues.
Acar does not disclose that the composition comprises extracellular vesicles or that the composition has less than 40 weight% of sticky imaging particles that are not associated with extracellular vesicles, where weight% is based on total composition weight.
However, with respect to claim 29, Jia discloses an imaging composition comprising:
Extracellular vesicles (exosomes) and imaging particles (SPION)
A therapeutic agent, curcumin. [Jia, Page 306, Figure 1]
With respect to claim 52, Jia discloses that the exosomes encapsulate the imaging particles. [Jia, Page 306, Figure 1]
Modifying the composition and method disclosed by Acar by encapsulating the composition within targeted exosomes results in the composition of claim 29 and 52, wherein the imaging composition comprises:
Extracellular vesicles (exosomes) encapsulating sticky imaging particles comprising:
imaging particles (SPION) and sticky elements comprising a peptide (AGO2) with 16 histidine residues;
A therapeutic agent (cisplatin);
wherein, the composition has less than 40 weight % of sticky imaging particles that are not associated with exosomes, as all the sticky imaging particles are encapsulated within the exosomes.
It would be obvious to one of ordinary skill in the art to modify the composition and method disclosed by Acar by encapsulating the composition within targeted exosomes and have a reasonable expectation of success. Acar discloses a composition comprising SPION imaging particles and a therapeutic agent, cisplatin. Jia discloses a targeted exosome encapsulating a composition comprising an SPION imaging particle and a therapeutic agent, curcumin. Accordingly, the combined teachings of Jia and Acar reasonably suggest that the composition comprising an SPION imaging particle and a therapeutic agent disclosed by Acar may be encapsulated in a targeted exosome. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Jia discloses that exosomes can carry nanomaterials and chemical agents across the BBB. [Jia, Abstract] Moreover, exosomes contain a large number of proteins, coding and noncoding RNAs, and lipids, and they play an important role in communication and transportation between cells. As carriers, exosomes are characterized by several features: low immunogenicity, biodegradable, non-toxic, strong cargo-loading and cargo protective capacity, and strong ability to cross the BBB. [Jia, Page 302, Col. 2, Paragraph 2] Therefore, one would have been motivated by the expectation that encapsulating the composition disclosed by Acar within targeted exosomes would enable the composition to be carried across the BBB when administered to a subject.
Response to Arguments
Applicant's arguments, filed 7/9/2026, have been fully considered but they are not persuasive.
Applicant asserts, “Thus, the primary citation of Guldris specifically teaches use of poly(acrylic acid) as an essential component. For instance, at page 363 Guldrus reports:
In order to apply magnetic nanoparticles (NPs) as MR labeling agents in cell tracking, IONs were synthesized by a hydrothermal method using poly( acrylic acid) (PAA) as a coating because of the high yield, magnetic response of the NPs, high stability in aqueous medium, and the possibilities the coating offers for further functionalization.
Clearly, based on such disclosure, no incentive would have existed to substitute in a material of Horak as proposed in the Office Action. No substantiating reasoning has been presented to provide for such substitution. Guldris clearly reports the importance of poly(acrylic acid).” [Remarks 7/9/2026, Page 8]
Applicant’s arguments are not persuasive because the cited excerpt does not describe PAA as essential or irreplaceable. The reference merely identifies the functional properties of PAA that support why PAA was chosen as the coating. However, the described properties were known in the art. The reference does not suggest that these properties are unique to PAA or contend that other coatings are incapable of achieving those same properties. The prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed. MPEP 2145(X)(D)(1). Guldris describes PAA as an excellent coating, but that description alone does not disclose that other coatings are not just as excellent.
On the contrary, the excerpt further supports the rejection of record because it describes the specific functional properties that make PAA a suitable coating. This teaching provides a POSITA with criteria for evaluating and selecting a suitable substitute coating. In view of this teaching, a POSITA would have had clear guidance on what properties to look for when considering alternative coatings like polyhistidine. Ultimately, PAA’s significance lies in the properties it imparts.
Finally, the relevant inquiry is not whether a POSITA would have been motivated to depart from using PAA as the coating. Rather, the relevant inquiry is whether a POSITA would have been motivated to modify the composition and method disclosed by Guldris (e.g., by substituting PAA with another coating having equivalent functional properties). A POSITA would have been motivated to explore other coatings that achieve those same functional properties as PAA because it is prima facie obvious to substitute equivalents known for the same purpose.
Conclusion
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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