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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/08/26 has been entered.
Response to Amendment
The amendment filed 04/08/26 has been entered. Claims 1, 3, 15, 16, 26-27, and 30 have been amended. Claims 2, 8-14, 17-22, 24-25, and 28 are in the original/ previously presented form. Claims 4-7, 23, 29, and 31 are cancelled. Claims 32-34 are newly presented. Thus, claims 1-3, 8-22, 24-28, 30, and 32-34 remain pending in the application. There were no objections or 112(b) rejections previously set forth in the Final Office Action mailed 01/30/26. Therefore, there are no objections or 112 rejections withstanding.
Claim Objections
Claim 16 is objected to because of the following informalities:
Claim 16 lines 1-2 reads “a method of delivering an agent in vivo to the brain of a subject comprising” and should likely read “a method of delivering an agent in vivo to [[the]] a brain of a subject comprising” to provide antecedent basis for the first recitation of brain in the independent claim
Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
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 1-3, 8-17, 19-22, 24-28, 30, and 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Dani et al. (U.S. PGPUB No. 2016/0310593), hereinafter Dani, in view of Humphries et al. (U.S. PGPUB No. 2011/0064792), hereinafter Humphries.
Regarding claim 1, Dani discloses a method of generating nanoscale heating and photomechanical effects in vivo at the blood-facing side of a blood-brain barrier (BBB) permeabilizing the blood-brain barrier in a subject (see [0051]: heat applied via laser and [0059]: for delivery to a subject brain such as to transfer the composition across the blood brain barrier) comprising:
administering to said subject a light-absorbing plasmonic noble metal nanoparticle (see [0020]: Dani’s method includes administering a liposome attached to a metal nanoparticle in vivo and [0038]: nanoparticles may be noble metal nanoparticles, which aligns with Applicant disclosure of “light absorbing” in the current Application’s [0005]) coupled to a targeting agent (a liposome, see [0049]: liposomes bound to antibodies can selectively attach to target cells/ molecules and see [0033]: specific agents, such as a ligands, can be embedded in the liposome); and
exposing said light-absorbing plasmonic noble metal nanoparticle to a short pulse laser signal (see [0020]: laser pulse train applied to liposome/ metal nanoparticle and [0036]: liposome is irradiated with laser pulses in the method of the disclosure), wherein absorbance (see [0041]: nanostructure of particles absorb desired wavelength/light and [0050-0053]: energy absorbed by particle releases a drug) of the short pulse laser signal (see [0020]: laser pulse train applied to liposome/ metal nanoparticle and [0036]: liposome is irradiated with laser pulses in the method of the disclosure) by said light-absorbing plasmonic noble metal nanoparticle (see [0020]: the method includes administering a liposome attached to a metal nanoparticle in vivo and [0038]: nanoparticles may be noble metal nanoparticles) results in localized disruption of the blood-brain barrier (see [0049]: liposomes may be incorporated into the nanoparticles of the disclosure. see [0059] and [0074-0075]: Specifically, as incorporated into the nanoparticles, trojan horse liposomes ‘disrupt’ the BBB to allow drugs/chemicals to pass into brain. Therefore, particle is targeted to BBB by trojan horse liposomes to ‘disrupt’ the barrier to deliver the energy released drug—again see [0050-0053]).
Dani is silent to specifically permeabilizing “tight junctions (TJ) of” the blood brain barrier, the method administering the nanoparticle coupled to a targeting “ligand that directs said light-absorbing plasmonic noble metal nanoparticle to the blood side of the blood-brain barrier (BBB)”, and the method results in localized “transient paracellular” disruption of the blood-brain barrier, “thereby increasing paracellular permeability to macromolecules without requiring transcytosis of the light-absorbing plasmonic noble metal nanoparticle across an intact barrier.”
However, Humphries teaches a method of generating nanoscale effects (see [0031-0034]: siRNAs comprise two RNA strands of 20 nucleotides, for a total of 40 nucleotides, generating effects at a nanoscale level) in vivo at the blood-facing side of a blood-brain barrier (BBB) (see [0021]: method delivery is systemic==blood side of BBB) permeabilizing tight junctions (TJ) of the blood-brain barrier in a subject (see [0015]: transient opening of BBB and [0035]: siRNA formulated to target tight junction to open BBB, and [0038-0043]), the method comprising administering a targeting ligand (see [0035]: siRNA formulated to target tight junction to open BBB and [0091]: composition that SiRNA binds to can include protein, making the siRNA+protein a targeting ligand) that directs a composition (see [0027]: active agent with siRNA and [0091]: targeting agent can be a protein) to the blood side of the blood-brain barrier (BBB) (see [0021] & [0035]: systemic delivery targets tight junctions on the blood size of the blood brain barrier), and the method results in localized transient paracellular disruption of the blood-brain barrier (see [0015]: transient opening of BBB and [0035]: siRNA formulated to target tight junction to open BBB, and [0038-0043]), thereby increasing paracellular permeability to macromolecules without requiring transcytosis of the composition across an intact barrier (see [0038-0048] & [0109-0115]: permeability enhanced to open the paracellular pathway of the BBB after 24 to 48hours and return to normal 72hours post delivery).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of generating nanoscale heating and photomechanical effects in vivo at the blood-facing side of a blood-brain barrier to permeabilize the blood-brain barrier via excitation of a nanoparticle coupled to a targeting agent as disclosed in Dani to use a targeting ligand as the targeting agent to permeabilize tight junctions (TJ) of the blood-brain barrier as taught by Humphries for the purpose of passing small molecules into the brain across the blood brain barrier via a reversible, transient, and size-selective opening of the BBB via the tight junctions (see [0038-0043]), thus achieving specifically permeabilizing “tight junctions (TJ) of” the blood brain barrier, the method administering the nanoparticle coupled to a targeting “ligand that directs said light-absorbing plasmonic noble metal nanoparticle to the blood side of the blood-brain barrier (BBB)”, and the method results in localized “transient paracellular” disruption of the blood-brain barrier, “thereby increasing paracellular permeability to macromolecules without requiring transcytosis of the light-absorbing plasmonic noble metal nanoparticle across an intact barrier.”
Regarding claim 2, the modified method of Dani teaches the method of claim 1, and Dani further discloses wherein said short pulse laser signal is a picosecond or nanosecond laser signal (see [0055-0056]: femtosecond laser can be applied at 1 picosecond pulse signals).
Regarding claim 3, the modified method of Dani teaches the method of claim 1, and Dani further discloses wherein said targeting agent is a receptor ligand, receptor ligand mimic, or an antibody (see [0033]: any agents that can be permeated into the liposome can be used, such as a receptor ligand), but, again, Dani is silent to the targeting agent being specifically a targeting “ligand”.
However, Humphries teaches a method of generating nanoscale effects (see [0031-0034]: siRNAs comprise two RNA strands of 20 nucleotides, for a total of 40 nucleotides, generating effects at a nanoscale level) in vivo at the blood-facing side of a blood-brain barrier (BBB) (see [0021]: method delivery is systemic==blood side of BBB) permeabilizing tight junctions (TJ) of the blood-brain barrier in a subject (see [0015]: transient opening of BBB and [0035]: siRNA formulated to target tight junction to open BBB, and [0038-0043]), the method comprising administering a targeting ligand (see [0035]: siRNA formulated to target tight junction to open BBB and [0091]: composition that SiRNA binds to can include protein, making the siRNA+protein a targeting ligand) that directs a composition (see [0027]: active agent with siRNA and [0091]: targeting agent can be a protein) to the blood side of the blood-brain barrier (BBB) (see [0021] & [0035]: systemic delivery targets tight junctions on the blood size of the blood brain barrier).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of generating nanoscale heating and photomechanical effects in vivo at the blood-facing side of a blood-brain barrier to permeabilize the blood-brain barrier via excitation of a nanoparticle coupled to a targeting agent as disclosed in Dani to use a targeting ligand as the targeting agent to permeabilize tight junctions (TJ) of the blood-brain barrier as taught by Humphries for the purpose of passing small molecules into the brain across the blood brain barrier via a reversible, transient, and size-selective opening of the BBB via the tight junctions (see [0038-0043]), thus achieving the targeting agent being specifically a targeting “ligand”.
Regarding claim 8, the modified method of Dani teaches the method of claim 1, and Dani further discloses wherein said subject is a human (see [0056]: method may be used in vivo with humans and [0065]: human models in vivo).
Regarding claim 9, the modified method of Dani teaches the method of claim 1, and Dani further discloses wherein said subject is a non- human animal (see [0056]: method may be used in vivo in tissue or organism and [0065]: animal models in vivo).
Regarding claim 10, the modified method of Dani teaches the method of claim 1, and Dani discloses further comprising administering to said subject a therapeutic or diagnostic agent ([0004]: a therapeutic or diagnostic agent may be delivered).
Regarding claim 11, the modified method of Dani teaches the method of claim 10, and Dani further discloses wherein said therapeutic or diagnostic agent is attached to said light-absorbing particle (see [0004]: therapeutic of diagnostic agent attached to liposome/ metal nanoparticle).
Regarding claim 12, the modified method of Dani teaches the method of claim 10, and Dani further discloses wherein said therapeutic or diagnostic agent is not attached to said light-absorbing particle (see [0005]: therapeutic or diagnostic agent can be attached to polymer-particle composition instead of metal nanoparticle).
Regarding claim 13, the modified method of Dani teaches the method of claim 1, and Dani further discloses wherein said laser signal is a near-infrared signal (see [0051]: method includes use of visible or infrared range, such as see [0052-0053]: near-infrared).
Regarding claim 14, the modified method of Dani teaches the method of claim 1, and Dani further discloses wherein said laser signal is a visible signal (see [0051]: method includes use of visible or infrared range)
Regarding claim 15, the modified method of Dani teaches the method of claim 1, and Dani further discloses wherein said light-absorbing particle is administered systemically (see [0059]: delivery to subject by intra-arterial/ intravenous, which are systemic administration methods).
Regarding claim 16, Dani discloses a method of delivering an agent in vivo to the brain of a subject (see [0051]: heat applied via laser and [0059]: for delivery to a subject brain such as to transfer the composition across the blood brain barrier) comprising:
(a) administering to said subject a light-absorbing plasmonic noble metal nanoparticle (see [0020]: Dani’s method includes administering a liposome attached to a metal nanoparticle in vivo and [0038]: nanoparticles may be noble metal nanoparticles, which aligns with Applicant disclosure of “light absorbing” in the current Application’s [0005]), wherein said light-absorbing plasmonic noble metal nanoparticle comprises a targeting agent (a liposome, see [0049]: liposomes bound to antibodies can selectively attach to target cells/ molecules and see [0033]: specific agents, such as a ligands, can be embedded in the liposome);
(b) administering to said subject an agent (see [0004]: therapeutic or diagnostic agent encapsulated in liposome targeting agent for delivery to subject); and
(c) contacting said light-absorbing plasmonic noble metal nanoparticle with a short pulse laser signal (see [0020]: laser pulse train applied to liposome/ metal nanoparticle and [0036]: liposome is irradiated with laser pulses in the method of the disclosure),
wherein absorbance (see [0041]: nanostructure of particles absorb desired wavelength/light and [0050-0053]: energy absorbed by particle releases a drug) of the short pulse laser signal (see [0020]: laser pulse train applied to liposome/ metal nanoparticle and [0036]: liposome is irradiated with laser pulses in the method of the disclosure) by said light-absorbing plasmonic noble metal nanoparticle (see [0020]: the method includes administering a liposome attached to a metal nanoparticle in vivo and [0038]: nanoparticles may be noble metal nanoparticles) results in localized disruption of the blood-brain barrier (see [0049]: liposomes may be incorporated into the nanoparticles of the disclosure. see [0059] and [0074-0075]: Specifically, as incorporated into the nanoparticles, trojan horse liposomes ‘disrupt’ the BBB to allow drugs/chemicals to pass into brain. Therefore, particle is targeted to BBB by trojan horse liposomes to ‘disrupt’ the barrier to deliver the energy released drug—again see [0050-0053]).
Dani is silent to administering the nanoparticle comprising a targeting “ligand that directs said light-absorbing plasmonic noble metal nanoparticle to a blood-brain barrier tight junction”, the method resulting in localized “transient paracellular” disruption of the blood-brain barrier “via perturbation of tight junctions of endothelial cells, thereby increasing paracellular permeability to macromolecules without requiring transcytosis of the light-absorbing particle across an intact blood-brain barrier”.
However, Humphries teaches a method of delivering an agent in vivo to the brain of a subject (see [0021] & [0035]: systemic delivery targets tight junctions on the blood size of the blood brain barrier) comprising administering a targeting ligand (see [0021] & [0035]: systemic delivery targets tight junctions on the blood size of the blood brain barrier) that directs a composition (see [0027]: active agent with siRNA and [0091]: targeting agent can be a protein) to a blood-brain barrier tight junction (see [0015]: transient opening of BBB and [0035]: siRNA formulated to target tight junction to open BBB, and [0038-0043]), the method resulting in localized transient paracellular disruption of the blood-brain barrier (see [0015]) via perturbation of tight junctions of endothelial cells (see [0002]: tight junctions are between endothelial cells such as in the blood-brain barrier, [0006-0007], [0022]. Perturbation of tight junctions of endothelial cells in [0035-0043]), thereby increasing paracellular permeability to macromolecules without requiring transcytosis of the composition across an intact blood-brain barrier (see [0038-0048] & [0109-0115]: permeability enhanced to open the paracellular pathway of the BBB after 24 to 48hours and return to normal 72hours post-delivery).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of delivering an agent in vivo to the brain of a subject to permeabilize the blood-brain barrier via excitation of a nanoparticle coupled to a targeting agent as disclosed in Dani to use a targeting ligand as the targeting agent to perturb tight junctions (TJ) of the blood-brain barrier in a subject as taught by Humphries for the purpose of passing small molecules into the brain across the blood brain barrier via a reversible, transient, and size-selective opening of the BBB (see [0038-0043]), thus achieving administering the nanoparticle comprising a targeting “ligand that directs said light-absorbing plasmonic noble metal nanoparticle to a blood-brain barrier tight junction”, the method resulting in localized “transient paracellular” disruption of the blood-brain barrier “via perturbation of tight junctions of endothelial cells, thereby increasing paracellular permeability to macromolecules without requiring transcytosis of the light-absorbing particle across an intact blood-brain barrier”.
Regarding claim 17, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said agent is a diagnostic agent (see [0004]: therapeutic or diagnostic agent encapsulated in liposome targeting agent for delivery to subject).
Regarding claim 19, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said agent is a therapeutic agent (see [0004]: therapeutic or diagnostic agent encapsulated in liposome targeting agent for delivery to subject).
Regarding claim 20, the modified method of Dani teaches the method of claim 19, and Dani further discloses wherein said therapeutic agent is an anti-cancer agent, such as a chemotherapeutic, a radiotherapeutic, an immunotherapeutic, or a gene therapeutic (see [0058], [0061]: therapeutic agent may be for chemotherapy and [0033]: may be gene therapeutic agent).
Regarding claim 21, the modified method of Dani teaches the method of claim 19, and Dani further discloses wherein said therapeutic agent is an antibiotic, an antifungal or an antiviral (see [0058]: therapeutic agent can be antibiotic).
Regarding claim 22, the modified method of Dani teaches the method of claim 19, and Dani further discloses wherein said therapeutic agent is a neurotherapeutic agent, such as an anti-dementia drug, an anti-neurodegenerative disease drug, an anti-edema agent such as glyburide, or a gene therapy agent such as AAV (see [0033]: any substance/ therapeutic agent that can be encapsulated in liposome can be delivered such as neuromodulators, neurotransmitters, gene therapy agents, etc.).
Regarding claim 24, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said subject is a human (see [0056]: method may be used in vivo with humans and [0065]: human models in vivo).
Regarding claim 25, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said subject is a non- human animal (see [0056]: method may be used in vivo in tissue or organism and [0065]: animal models in vivo).
Regarding claim 26, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said agent is attached to said light-absorbing plasmonic noble metal nanoparticle (see [0004]: therapeutic or diagnostic agent encapsulated in liposome/ targeting agent for delivery to subject and [0020]: the method includes administering a liposome attached to a metal nanoparticle in vivo and [0038]: nanoparticles may be noble metal nanoparticles. Thus, the therapeutic agent is attached to the liposome/ light-absorbing particle).
Regarding claim 27, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said agent is not attached to said light-absorbing plasmonic noble metal nanoparticle (see [0005]: therapeutic or diagnostic agent can be attached to polymer-particle composition instead of metal nanoparticle).
Regarding claim 28, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said laser signal is a near-infrared signal (see [0051]: method includes use of visible or infrared range, such as see [0052-0053]: near-infrared).
Regarding claim 30, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said light-absorbing plasmonic noble metal nanoparticle and/or said agent are administered systemically (see [0059]: delivery to subject by intra-arterial/ intravenous, which are systemic administration methods).
Regarding claim 33, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said light-absorbing particle is administered intravenously, intra-arterially, intrathecally, or retro-orbitally (see [0059]: delivery to subject by intra-arterial/ intravenous).
Regarding claim 34, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said light-absorbing particle is administered intravenously, intra-arterially, intrathecally, or retro-orbitally (see [0059]: delivery to subject by intra-arterial/ intravenous).
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Dani in view of Humphries as applied to claim 17 above, and further in view of MAEKAWA et al. (U.S. PGPUB No. 2019/0099382), hereinafter Maekawa.
Regarding claim 18, the modified method of Dani teaches the method of claim 17, but Dani is silent to “wherein said diagnostic agent is a dye, a fluorophore, chromophore, a contrast agent, or a radionuclide.”
However, Maekawa teaches a method of locally disrupting the blood brain barrier by administering a nanoparticle (see [0203]: transferrin-bound nanoparticles administered) and administering a diagnostic agent (see [0147]: nanoparticles comprising imaging agents delivering to target site), wherein said diagnostic agent is a dye, a fluorophore, and chromophore, a contrast agent, or a radionuclide (see [0145-0147]: imaging agents such as contrast agents can be included and delivered by nanoparticle).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the diagnostic agent disclosed by Modified Dani to be a contrast agent as taught by Maekawa for the purpose of monitoring the effect of the therapy on the target site (see [0145]), thus achieving “wherein said diagnostic agent is a dye, a fluorophore, chromophore, a contrast agent, or a radionuclide.”
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Dani in view of Humphries as applied to claim 1 above, and further in view of Cui et al. (U.S. PGPUB No. 2005/0129679), hereinafter Cui.
Regarding claim 32, the modified method of Dani teaches the method of claim 1, but Dani is silent to “wherein the targeting ligand is a transferrin antibody, a JAM-A antibody, a Claudin-5 antibody, or a ZO-1 antibody.”
However, Humphries teaches a method of generating nanoscale effects (see [0031-0034]: siRNAs comprise two RNA strands of 20 nucleotides, for a total of 40 nucleotides, generating effects at a nanoscale level) in vivo at the blood-facing side of a blood-brain barrier (BBB) (see [0021]: method delivery is systemic==blood side of BBB) permeabilizing tight junctions (TJ) of the blood-brain barrier in a subject (see [0015]: transient opening of BBB and [0035]: siRNA formulated to target tight junction to open BBB, and [0038-0043]), the method comprising administering a targeting ligand (see [0035]: siRNA formulated to target tight junction to open BBB and [0091]: composition that SiRNA binds to can include protein, making the siRNA+protein a targeting ligand) that directs a composition (see [0027]: active agent with siRNA and [0091]: targeting agent can be a protein) to the blood side of the blood-brain barrier (BBB) (see [0021] & [0035]: systemic delivery targets tight junctions on the blood size of the blood brain barrier), wherein the targeting ligand targets Claudin-5 (see [0006-0007], [0009-0010], and [0079-0080]: several ways to target claudin proteins are contemplated, such as, see [0082], [0126-0128]: via AAV-mediated delivery).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of generating nanoscale heating and photomechanical effects in vivo at the blood-facing side of a blood-brain barrier to permeabilize the blood-brain barrier via excitation of a nanoparticle coupled to a targeting agent as disclosed in Dani to use a targeting ligand as the targeting agent as taught by Humphries for the purpose of passing small molecules into the brain across the blood brain barrier via a reversible, transient, and size-selective opening of the BBB (see [0038-0043]), thus achieving “the targeting ligand” targets Claudin-5.
Dani in view of Humphries is silent to wherein the targeting ligand “is a transferrin antibody, a JAM-A antibody, a Claudin-5 antibody, or a ZO-1 antibody.”
However, Cui teaches a method of opening tight-junctions (see [0018-0021]) utilizing a targeting ligand, wherein the targeting ligand is a transferrin antibody, a JAM-A antibody, a Claudin-5 antibody, or a ZO-1 antibody (see [0031]: “The antibodies specifically recognize functional portions of the JAM, occludin or claudin protein, and are therefore useful for blocking interactions between these proteins, or permeabilizing mucosal epithelial target cells when administered in vivo. ”).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the targeting ligand directed to Claudin-5 taught by Dani in view of Humphries to comprise an antibody as taught by Cui for the purpose of permeabilizing the target cells of the specific tight junction while combining therapeutic benefits of an antibody to the cells (see [0031]), thus achieving wherein the targeting ligand “is a transferrin antibody, a JAM-A antibody, a Claudin-5 antibody, or a ZO-1 antibody.”
Response to Arguments
Applicant's arguments filed 04/08/26 have been fully considered but they are not persuasive.
Pages 6-7 of Applicant remarks direct arguments to the combination of Dani in view of Maekawa and are therefore moot in view of the new rejection under Dani in view of Humphries.
On pages 7-8, Applicant argues that the current invention has achieved unexpected results relative to the prior art including Humphries and Dani. Specifically, Applicant asserts that the current invention achieves “immediate” BBB opening via physical TJ perturbation that would be unexpected compared to Dani’s post-crossing BBB release and Humphries’ “delayed” release. The examiner was not persuaded by this argument and has therefore maintained a rejection using the argued prior art of Dani and Humphries.
First, unexpected results need to be commensurate in scope with the claimed invention (see MPEP § 716.02(d)). The claims do not recite time constraints (i.e.: minutes-scale as mentioned by Applicant on page 7) for the opening of the blood brain barrier via TJ perturbation, rendering this argument of unexpected results non-persuasive. Thus, Applicant has failed to meet the burden to establish that the alleged results are unexpected (see MPEP § 716.02(b).I).
Next, the examiner asserts that the combination of Dani in view of Humphries would have expected beneficial results. For example, Dani discloses that excitation of a nanoparticle with a targeting agent enhances drug delivery across the blood brain barrier, such as in [0053]. Humphries teaches that targeting the tight junctions of the blood brain barrier enhances drug delivery, such as in [0015] & [0038-0043]. Therefore, the combination of Dani and Humphries would have expected beneficial results of a more efficient/quicker/effective drug delivery to the brain by combining two separate methods shown to increase drug delivery across the BBB —i.e.: light-aided transport as in Dani and cell-targeted transport as in Humphries. Expected beneficial results of Dani in view of Humphries would be obvious to one of ordinary skill in the art because the combined therapy would combine the benefits of each of the individual therapies. Thus, the examiner was not persuaded by the argument of unexpected results and instead argues that the combination results in expected beneficial results (see MPEP § 716.02(c).II: “Expected beneficial results are evidence of obviousness of a claimed invention”). Therefore, again, the examiner was not persuaded by the argument and maintained the prior art as previously referenced.
No further arguments were presented. Therefore, the examiner also maintained the subsequent depending claim rejections under the previously referenced prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHLEEN PAIGE FARRELL whose telephone number is (571)272-0198. The examiner can normally be reached M-F: 730AM-330PM Eastern Time.
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/KATHLEEN PAIGE VOKES/Examiner, Art Unit 3783
/MICHAEL J TSAI/Supervisory Patent Examiner, Art Unit 3783
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