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 .
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.
Election/Restrictions
Applicant’s election of Group II, claims 3-10 in the reply filed on 24 October 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-2 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 24 October 2025.
Note Regarding Abbreviations
Claim 3 recites the abbreviations “Tf”, “RVG”, and “PLGA.” These abbreviations do not appear to have been defined in the claims. Nevertheless, the specification defines these abbreviations in the following manner:
Tf is defined as transferrin, as of page 2 of the instant specification, last full paragraph, relevant text reproduced below.
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RVG is defined as rabies virus glycoprotein, as of page 2 of the instant specification, relevant text reproduced above.
PLGA is a well-known acronym meaning poly(lactide-co-glycolide). See the instant specification on page 5, second paragraph.
Claim 3, 8th line recites “1000 rpm.” In this case, “rpm” is a well-known abbreviation for revolutions per minute.
Claim 8 recites the acronym “PBS.” While this acronym is not defined in the application, it is a common, well-known acronym in the biological sciences and refers to phosphate buffered saline. The examiner understands PBS to have a pH and osmolality similar to that of blood. See e.g. Thorat et al. (Pharmaceutical Research, Vol. 36:98, 2019, pages 1-11) for a further explanation of this issue.
As such, the above-indicated acronyms are understood by the examiner to be definite.
Claim Rejections - 35 USC § 112(b) – Indefiniteness
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 3-10 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 3, third line, recites “reduced protein diet (RPD).” The claim further recites that a solution comprising 1-12% of reduced protein diet in isopropyl alcohol is formed. As best understood by the examiner, the ordinary definition of the phrase “reduced protein diet” refers to a diet which comprises a lower-than-normal intake of protein. A reduced protein diet, also referred to as a low protein diet, is often prescribed for kidney disease. See e.g. Noce et al. (Cell Death Discovery, Vol. 2, 2016, pages 1-11).
It is unclear how a solution comprising 1-12% of reduced protein diet in isopropyl alcohol can be formed. This is especially the case because (a) the skilled artisan would have expected a reduced protein diet to have contained carbohydrates that would not have been soluble in isopropyl alcohol, and (b) isopropyl alcohol is toxic and would not have been appropriate for human ingestion. See Clark (Journal of Emergency Nursing, Vol. 36 Issue 1, January 2010, pages 81-82) regarding isopropyl alcohol toxicity.
For the purposes of examination under prior art, the examiner will examine the claims with the understanding that the abbreviation “RPD” refers to risperidone rather than “reduced protein diet.” Support for this position is determined in view of the fact that the title of the instant application relates to risperidone. Also, much of the discussion on pages 3-4 of the specification concerns atypical antipsychotics, and the skilled artisan would have been aware that risperidone is an atypical antipsychotic.
Claims 3-10 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 3 recites a “solid liquid nanoparticle (SLN)” dispersion. It is unclear as to how a nanoparticle can be both solid and liquid concurrently. As best understood by the examiner, nanoparticles must be either solid or liquid and cannot be both concurrently.
For the purposes of examination under prior art, the examiner will examine the term “SLN” as if it refers to a nanoparticle dispersion wherein the nanoparticles are solid but are suspended in a liquid medium.
Claims 3-10 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 3, sixth line of claim, recites an aqueous surfactant solution. This would appear to require that the surfactant is present. However, the claim also recites an 0-2% range of the surfactant, indicating that the surfactant need not be present and is optional. As such, it is unclear if the surfactant is required or optional.
For the purposes of examination under prior art, the examiner will examine the claims with the understanding that the surfactant is optional.
Claims 3-10 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 3 recites the following, as of the last three lines, which are reproduced below with annotation by the examiner.
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As such, it is unclear as to what moiety the recited carboxylic acid terminal groups are attached. There is also a lack of antecedent basis of addition or formation of PLGA nanoparticles earlier in the claim, and the claim does not recite the addition of PLGA.
For the purposes of examination under prior art, the examiner will examine the claim with the understanding that carboxylic acid terminated PLGA is added to the prepared organic solution along with risperidone and lipid in the dissolving step. The examiner also understands that the carboxylic acid terminal groups activated in the last step of claim 1 are that of the acid-terminated PLGA.
Claim 4 is 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 4 contains the trademark/trade name Compritol 888. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See MPEP 2173.05(u). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a type of lipid glyceride and, accordingly, the identification/description is indefinite.
Specification
The instant specification defines the acronym “RPD” as “Reduced protein diet” as of multiple locations on page 6 of the specification. Applicant should consider whether this is correct.
Applicant may amend the specification to disclose that “RPD” is “risperidone” rather than “reduced protein diet.” Such an amendment is would appear to be permissible as the correction of an obvious error. See MPEP 2163.07(II).
Claim Interpretation
Claim 8 recites the language “1 ml, 1 mg/ml.” The examiner understands this language to refer to “1 mL of 1 mg/mL” of transferrin or rabies virus glycoprotein.
Relevant Prior Art – No Rejection
The examiner has not rejected the instant claims over prior art. The examiner has presented the following rationale for not rejecting the claims over prior art.
First, the examiner notes that risperidone was known prior to the effective filing date as an atypical antipsychotic. As such, the skilled artisan would have been motivated to have delivered risperidone to the brain because the location at which an antipsychotic drug acts is in the brain. In support of this position, the examiner cites Patel et al. (Journal of Drug Targeting, Vol. 19(6), 2011, pages 468-474). This reference is drawn to risperidone-loaded solid lipid nanoparticles, as of Patel, title and abstract. Patel achieves delivery to the brain by formulating the risperidone into solid lipid nanoparticles and delivering via the intranasal route. Patel differs from the claimed invention because Patel does not appear to teach PLGA, and does not appear to teach the use of rabies virus glycoprotein and transferrin as targeting ligands.
Secondly, the examiner takes the position that the use of rabies virus glycoprotein for brain targeting was also known in the art. In support of this position, the examiner cites Chung et al. (Pharmaceutics, Vol. 12(93), 2019, pages 1-16). This reference is drawn to poly(lactic-co-glycolic) acid particles modified with RVG29 rabies virus glycoprotein for administration of an active agent (that is not risperidone) to the brain and spinal cord.
Chung differs from the claimed invention at least because (a) Chung does not teach risperidone (but teaches a different drug instead), (b) Chung does not teach transferrin, and (c) Chung teaches an avidin-biotin linkage to link the rabies virus glycoprotein to the exterior of the particle, as of Chung, page 3, section 2.2. This differs from the claimed mode of linkage of the rabies virus glycoprotein to the exterior of the particle. This is because the avidin-biotin linkage is a non-covalent linkage. In contrast, the linkage formed via coupling with a carbodiimide such as ethyl-2-(3-dimethylaminopropyl)carbodiimide is a covalent linkage.
As an additional relevant reference, the examiner cites Hong et al. (Drug Delivery, Vol. 25, No. 1, 2018, pages 1886-1897). Hong et al. (hereafter referred to as Hong) is drawn to a nanoparticle for delivery across the blood brain barrier, as of Hong, page 1886, title and abstract. Hong teaches the following particle, as of page 1887, right column, figure 1, reproduced below – the examiner recommends viewing the figure in its original color.
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Hong differs from the claimed invention at least for the following reasons.
First, Hong does not teach risperidone.
Secondly, the particle of Hong, while comprising PLGA, does not appear to comprise a lipid. As per the explanation as to how the indefinite claims are interpreted as set forth in the rejections above under 35 U.S.C. 112(b), the examiner has interpreted the claims as requiring both PLGA and a lipid.
Third, the particle of Hong comprises polyethylene glycol (PEG), which is not recited by the instant claims.
Fourth, in the particle of Hong, the active agent (which is bacitracin and is abbreviated as “BA”) is covalently bound to the polymer, which is not the case in the instantly claimed invention.
Fifth, what is actually taught by Hong is RVG29, which appears to be a peptide derived from rabies virus glycoprotein, not rabies virus glycoprotein itself, as of Hong, page 1887, right column, section 2.1.1. It is unclear if the RVG29 of Hong would have attached to sugar molecules and met the requirement of being a glycoprotein.
Sixth, Hong does not appear to specifically teach the use of carbodiimides and N-hydroxysulfosuccinimide.
Seventh, it appears that Hong first attaches RVG29 to the PLGA prior to formulating the nanoparticle. This order of steps differs from the claimed order of steps, in which the nanoparticle is formed first, and the RVG attached last.
The examiner provides the following note regarding point (f) above. It is the examiner’s position that under ordinary circumstances, changes in the order of steps are not sufficient to overcome a prima facie case of obviousness. See MPEP 2144.04(IV)(C). However, in this case, the art would appear to teach away from formulating the nanoparticle first and subsequently attaching ligands via carbodiimide chemistry after the nanoparticle has been formed. This is because in the claimed method, the carbodiimide reactions occur when the nanoparticle is suspended in water. In contrast, the prior art teaches that carbodiimide and N-hydroxysulfosuccinimide reaction intermediates can suffer from hydrolysis. In support of this position, the examiner cites Sigma-Aldrich (
https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/354/536/an1260en-ms.pdf?srsltid=AfmBOoooamvdbOpkfw7dDf6vZNBOqQsUnDERAhnnb9obq76l26dtv3wX, accessed 19 November 2025, 4 printed pages, originally published June 2022). Sigma-Aldrich teaches the following, on page 1, left column, relevant text reproduced below with annotation by the examiner.
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In view of the tendency of carbodiimide intermediates to undergo hydrolysis, the skilled artisan would not have been motivated to have attached agents to the exterior of the particle using carbodiimide chemistry in an aqueous environment, which is what was done by the claimed method. (Despite the fact that Sigma-Aldrich indicates that N-hydroxysulfosuccinimide hydrolyzes more slowly than N-hydroxysuccinimide without the sulfo group, the skilled artisan would skill have been motivated to have had the carbodiimide avoid water because N-hydroxysulfosuccinimide still hydrolyzes in the presence of water). In contrast, in the claimed method, applicant has proceeded contrary to the accepted wisdom in the art and has conducted carbodiimide/N-hydroxysulfosuccinimide chemistry on particles suspended in water and has successfully achieved coupling of rabies virus glycoprotein and transferrin. Proceeding contrary to the accepted wisdom in the art is evidence of non-obviousness. See MPEP 2145(X)(D)(3).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ISAAC SHOMER whose telephone number is (571)270-7671. The examiner can normally be reached 7:30 AM to 5:00 PM Monday Through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Frederick F Krass can be reached at (571)272-0580. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612