DETAILED ACTION
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)(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.
Claims 23, 24, 30, 31, 33, 34, 36-41, 43 and 44 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Perez et al. (US 2021/0113715).
Perez describes a nanoparticle useful in diagnosing, detecting and treating cancer.
Perez’s nanoparticle has a generic structure of a core, wherein the core comprises an iron oxide; a shell surrounding the core, wherein the shell comprises at least one polymer; and at least one targeting moiety attached to the shell (see abstract and claim 1).
The targeting moiety is to be a ligand that improves treatment outcomes via facilitating the transcytosis of the nanoparticle across biological barriers such as the blood brain barrier (BBB) (see [0188]). An exemplified nanoparticle is an aginopep-feraheme (feraheme is iron oxide, see [01896]) nanoparticle wherein an angiopep ligand is attached to the surface of a feraheme nanoparticle (see [0039, 0197], Figure 27). Angiopep ligands, such as angiopep-2, bind to low-density lipoprotein receptor-related protein 1 (LRP1) (see [0197]) (see instant claims 23, 34 and 44). LRP1 is highly expressed in brain endothelial cells of the BBB and upon binding of the angiopep to the BBB, the whole complex is transported across the endothelial membrane via transcytosis (see [1097]) (see instant claims 23, 24, 30 and 44).
Combinations of angiopep ligands (or other ligand types that interact with other receptors of the cell surface, e.g. heptamethine carbocyanine, folic acid, etc; see [0188, 0192]) may be attached to the nanoparticle surface thereby disclosing a nanoparticle having at least two ligands of a ligand type on the nanoparticle surface (see instant claims 31, 36, 37(c)).
The polymer shell of the nanoparticle includes polysaccharides and polymers such as dextran (see [0248]). It is noted that the instant claims identify dextran as a “polymer brush” (see instant claim 33).
The nanoparticle is to comprise a drug (see claim 32) (see instant claim 40).
Excipients are envisaged such as polyethylene glycol and polyvinylpyrrolidone as formulants (see [0336]) (see instant claim 44)
Regarding the limitation that the method be for “reducing amyloid-b and/or tau levels”, or for “treating or preventing Alzheimer’s disease in the patient”, or “the binding of the nanoparticle or microparticle to the endothelial cell surface results in an increase in the expression of LRP-1 in said endothelial cell” (see instant claims 23, 38, 39, 43 and 44), these are necessary outcomes of performing the prior art method. Albeit such outcomes are not recognized this is not mitigating because the prior art discloses a method identical to that claimed and so any outcome claimed must also be present in the prior, just unrecognized. Under the principles of inherency, if a prior art method, in its normal and usual operation, necessarily performs the method claimed, then the method claimed will be considered to be anticipated by the prior art method. See MPEP 2112.02(II).
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.
Claims 23, 24 and 27-44 is/are rejected under 35 U.S.C. 103 as being unpatentable over Holler et al. (US 2020/0206304; of record)
Holler teaches methods for the efficient delivery of compositions across the blood brain barrier (BBB) for the reduction of amyloid plaques in the brain in patients suffering from Alzheimer’s disease (see instant claims 38, 39 and 44). Compositions for transiting across the BBB include nanosystems include micelles, liposomes, polymeric nanoparticles (polymersomes) and crystalline nanoparticles like iron oxide (see [0507]) (see instant claim 32). The nanosystem is to have a ligand, such as angiopep-2, conjugated to the surface (see [0122, 0472] and claim 3). It is taught that angiopep-2 is utilized in nanoparticle systems to bind LRP1 which enables the transit of the nanoparticles across endothelial cells of the BBB (see [0122]) (see instant claims 23, 24, 27(i), 28, 30, 34). More than one ligand type may be attached to the nanoparticle, e.g. transferring ligan, peptides, etc (see [0124]) thereby suggesting at least 2 ligand types attached to nanoparticle surface (see instant claims 31, 36 and 37(a)). In some embodiments, the ligand may be attached to the surface of the nanoparticle via a chemical linker such as polyethylene glycol (PEG) (see [0006] and claim 10) (see instant claims 42. Moreover, the attachment of PEG or polylysine (polyamino acid) (see [0006]) “polymer brush” polymers according to instant claim 41 (and claim 33).
The nanoparticle may include a drug that is useful against Alzheimer’s disease such as donepezil and galantamine (see [0163]) (see instant claim 27(ii)). The drug may be delivered by encapsulation within the nanoparticle (see [0015]) (see instant claim 40).
The method may include pharmaceutically acceptable carrier or excipients (see [0021, 0200]) (see instant claims 29 and 44).
Regarding instant claim 35, the equation for ligand type on the surface is noted but is not seen as providing any detail at to the outcome of the equation or limit the invention so as to define a number of ligand types available for bonding with the nanoparticle or microparticle..
Regarding instant claim 43 and the limitation that binding of “the nanoparticle or microparticle to the endothelial cell surface results in an increase in the expression of LRP-1 in said endothelial cell”, this is a necessary outcome of performing the prior art method accord to Holler. Albeit such an outcome is not recognized by the prior art, because the general method claimed is overlapping with the prior art, such an outcome would be implicit to the process (although unrecognized).
The only difference between Holler and the instant claims is that Holler does not teach the specific combination of components as claimed in a single embodiment, or with sufficient specificity to be anticipatory. The specific combination of features claimed is disclosed within the teaching of Holler, but ‘such ‘picking and choosing’ within several variable does not necessarily give rise to anticipation. Where, such as here, the reference does not provide any explicit motivation to select this specific combination of variables, anticipation cannot be found. However, “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” See MPEP 2141(I).
Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in absence of evidence to the contrary.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 38 and 39 rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed had possession of the claimed invention.
Claim 38 recites “…the method is a method of treating or preventing Alzheimer’s disease”. However, the specification as filed does not convery that Applicant was in possession of a method that ‘prevents’ Alzheimer’s disease. Aside from generally stating such the specification provides no written description as to how one would go about ‘preventing’ such. As Applicant has not clearly articulated how to prevent Alzheimer’s disease nor shown any outcomes reflective of such, the claims lack proper written description.
Claim 39 is rejected for the same reason as claim 39 recites a “…method of treating or preventing cerebral angiopathy in the patient.” As with Alzheimer’s disease, the specification as filed does not have written support for how one would go about achieving such and provides no nexus that administration of the nanoparticle method would in fact achieve said end result.
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.
Claims 27, 30, 31, 32, 35, 37, 40 and 41 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Regarding claims 27, 30, 31, 32, 37, 40 and 41 all recite the term “preferably” (or “more preferably” or “most preferably”). However, “preferably” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 35 recites the following equation:
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54
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. However, the claim does not provide a solution to the ligand type and thus there is no way of understanding what is being claimed or how it relates to the nanoparticle. Further, given that the parameters are unlimited and undefined, the ligand type appears to extend indefinitely as there is no limitation otherwise. Clarification as to what this equation means in regards to the ligand type on the surface is requested.
Regarding claims 40 and 41, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 41, dependent from claim 23, recites “wherein the polymer brush comprises…”. However, claim 23 does not recite “polymer brush”. This term lacks antecedent basis.
Potentially Relevant Prior Art
Gajbhiye et al., Colloids and Surfaces B Biointerfaces 187, 2020, 10 pages
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE A PURDY whose telephone number is (571)270-3504. The examiner can normally be reached from 9AM to 5PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Bethany Barham, can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE A PURDY/Primary Examiner, Art Unit 1611