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 .
Response to Amendment
The amendment filed 12/01/25 has been entered. Claims 1, 16, 18 have been amended. Claims 2-5, 8-15, 17, 19-22, and 24-30 are in the original/ previously presented form. Claims 6-7 and 23 are cancelled. Claim 31 is newly presented. Thus, claims 1-5, 8-22, and 24-31 remain pending in the application. Applicant’s amendments to the Drawings and Claims have overcome each and every objection previously set forth in the Non-Final Office Action mailed 07/30/25.
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 1-5, 8-22, and 24-30 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 MAEKAWA et al. (U.S. PGPUB No. 2019/0099382), hereinafter Maekawa.
Regarding claim 1, Dani discloses a method of generating nanoscale heating and photomechanical effects in vivo at the blood-brain barrier 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 particle, such as a 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—thus light absorbing as disclosed in the current Application’s [0005]), wherein said light-absorbing particle 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) that directs said light-absorbing particle to target the blood brain barrier (see [0059] and [0074-0075]: agents such as Trojan horse liposomes can be used to transfer chemicals across the blood-brain barrier); and
(b) contacting said light-absorbing particle 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 particle (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 the light absorbing particle comprising a targeting agent specifically comprises a targeting “ligand” that directs said light absorbing particle “to a blood-brain barrier tight junction, JAM-A, Claudin-5, ZO-1, or transferrin”
However, Maekawa teaches a method of locally disrupting the blood brain barrier administering a nanoparticle (see [0203]: transferrin-bound nanoparticles administered), wherein said nanoparticle comprises a targeting ligand (see [0131-0134]: substances may be bound to nanoparticle such as a targeting ligand) that directs said nanoparticle to a blood-brain barrier tight junction, JAM-A, Claudin-5, ZO-1, or transferrin (see [0135]: examples of targeting ligand may include, see [0137]: transferrin. See [0138]: nanoparticles with bonded transferrin are capable of passing through blood brain barrier to deliver drugs. See [0222]: transferrin is successfully bonded to nanoparticle and [0217]: transferrin bonded nanoparticles result in best disruption of 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 targeting agent of the nanoparticle utilized in the method comprising administering a light-absorbing nanoparticle disclosed in Dani to be specifically a targeting ligand directing the particle to transferrin as taught by Maekawa for the purpose of using a targeting agent known in the art to be efficient at passing the blood brain barrier to deliver a drug with minimized adverse side effects (see [0207], [0210], and [0217]), thus achieving the light absorbing particle comprising a targeting agent specifically comprises a targeting “ligand” that directs said light absorbing particle “to a blood-brain barrier tight junction, JAM-A, Claudin-5, ZO-1, or transferrin”
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 (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, Maekawa teaches a method of locally disrupting the blood brain barrier administering a nanoparticle (see [0203]: transferrin-bound nanoparticles administered), wherein said nanoparticle comprises a targeting ligand (see [0131-0134]: substances may be bound to nanoparticle such as a targeting ligand)
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 receptor ligand targeting agent of the nanoparticle utilized in the method comprising administering a light-absorbing nanoparticle disclosed in Dani to be specifically a targeting ligand as taught by Maekawa for the purpose of using a targeting agent known in the art to be efficient at passing the blood brain barrier and to deliver a drug with minimized adverse side effects (see [0207], [0210], and [0217]), thus achieving the targeting agent being specifically a targeting “ligand”.
Regarding claim 4, the modified method of Dani teaches the method of claim 1,and Dani further discloses wherein said targeting agent is a receptor ligand mimic (see [0033]: any agent permeated into liposome such as receptor ligands, [0043]: ligands such as long-chain alkyl thiols—alkanethiols, etc., and [0049]: liposomes may selectively attach to targets), but, again, Dani is silent to the targeting agent being specifically a targeting “ligand”.
However, Maekawa teaches a method of locally disrupting the blood brain barrier administering a nanoparticle (see [0203]: transferrin-bound nanoparticles administered), wherein said nanoparticle comprises a targeting ligand (see [0131-0134]: substances may be bound to nanoparticle such as a targeting ligand)
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 receptor ligand mimic targeting agent of the nanoparticle utilized in the method comprising administering a light-absorbing nanoparticle disclosed in Dani to be specifically a targeting ligand as taught by Maekawa for the purpose of using a targeting agent known in the art to be efficient at passing the blood brain barrier and to deliver a drug with minimized adverse side effects (see [0207], [0210], and [0217]), thus achieving the targeting agent being specifically a targeting “ligand”.
Regarding claim 5, the modified method of Dani teaches the method of claim 1, and Dani further discloses wherein said targeting agent is an antibody (see [0033]: any agents that can permeate into liposome can be used, such as an antibody) but, again, Dani is silent to the targeting agent being specifically a targeting “ligand”.
However, Maekawa teaches a method of locally disrupting the blood brain barrier administering a nanoparticle (see [0203]: transferrin-bound nanoparticles administered), wherein said nanoparticle comprises a targeting ligand (see [0131-0134]: substances may be bound to nanoparticle such as a targeting ligand)
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 antibody targeting agent of the nanoparticle utilized in the method comprising administering a light-absorbing nanoparticle disclosed in Dani to be specifically a targeting ligand as taught by Maekawa for the purpose of using a targeting agent known in the art to be efficient at passing the blood brain barrier and to deliver a drug with minimized adverse side effects (see [0207], [0210], and [0217]), 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, such as intravenously, intra-arterially, intrathecally, or retro-orbitally (see [0059]: delivery to subject by intra-arterial, intravenous, other administration).
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 a composition across the blood brain barrier) comprising:
(a) administering to said subject a light-absorbing particle (see [0020]: the method includes administering a liposome attached to a metal nanoparticle in vivo and [0038]: nanoparticles may be noble metal nanoparticles —thus light absorbing as disclosed in the current Application’s [0005]), wherein said light-absorbing particle 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) that directs said light-absorbing particle to target the blood brain barrier (see [0059] and [0074-0075]: agents such as Trojan horse liposomes can be used to transfer chemicals across the blood-brain barrier); and
(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 particle 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 particle (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 the light absorbing particle comprising a targeting agent specifically comprises a targeting “ligand” that directs said light absorbing particle “to a blood-brain barrier tight junction, JAM-A, Claudin-5, ZO-1, or transferrin”
However, Maekawa teaches a method of locally disrupting the blood brain barrier administering a nanoparticle (see [0203]: transferrin-bound nanoparticles administered), wherein said nanoparticle comprises a targeting ligand (see [0131-0134]: substances may be bound to nanoparticle such as a targeting ligand) that directs said nanoparticle to blood-brain barrier tight junction or JAM-A, Claudin-5, ZO-1, or transferrin (see [0135]: examples of targeting ligand may include, see [0137]: transferrin. See [0138]: nanoparticles with bonded transferrin are capable of passing through blood brain barrier to deliver drugs. See [0222]: transferrin is successfully bonded to nanoparticle and [0217]: transferrin bonded nanoparticles result in best disruption of 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 targeting agent of the nanoparticle utilized in the method comprising administering a light-absorbing nanoparticle disclosed in Dani to be specifically a targeting ligand directing the particle to transferrin as taught by Maekawa for the purpose of using a targeting agent known in the art to be efficient at passing the blood brain barrier to deliver a drug with minimized adverse side effects (see [0207], [0210], and [0217]), thus achieving the light absorbing particle comprising a targeting agent specifically comprises a targeting “ligand” that directs said light absorbing particle “to a blood-brain barrier tight junction, JAM-A, Claudin-5, ZO-1, or transferrin”
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 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 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.”
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 particle (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 particle (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 29, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said laser signal is a visible signal (see [0051]: method includes use of visible or infrared range).
Regarding claim 30, the modified method of Dani teaches the method of claim 16, and Dani further discloses wherein said light-absorbing particle and/or said agent are administered systemically, such as intravenously, intra- arterially, intrathecally, or retro-orbitally (see [0059]: delivery to subject by intra-arterial, intravenous, other administration).
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Humphries et al. (U.S. PGPUB No. 2011/0064792), hereinafter Humphries, in view of Dani (U.S. PGPUB No. 2016/0310593).
Regarding claim 31, Humphries discloses a method for using a targeting ligand that directs said targeting ligand to a blood-brain barrier tight junction (see [0035]: siRNA formulated to target tight junction to open BBB), JAM-A, Claudin-5, ZO-1, or transferrin, wherein the targeting ligand results in localized transient opening 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]). Further, Humphries discloses that the effect of the therapy is enhanced by increasing permeability at the tissue delivery site (see [0050-0052]).
Humphries is silent to the method “of generating nanoscale heating and photomechanical effects in vivo at” the blood-brain barrier of a subject “comprising: (a) administering to said subject a light-absorbing particle, such as a plasmonic noble metal nanoparticle, wherein said light-absorbing particle comprises” the targeting ligand; and “contacting said light-absorbing particle with a short pulse laser signal, wherein absorbance of the short pulse laser signal by said light-absorbing particle results in” localized transient opening of the blood-brain barrier.
However, Dani teaches a method of generating nanoscale heating and photomechanical effects in vivo at the blood-brain barrier 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 particle, such as a 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—thus light absorbing as disclosed in the current Application’s [0005]), wherein said light-absorbing particle 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) that directs said light-absorbing particle to the blood-brain barrier (see [0059] and [0074-0075]: agents such as Trojan horse liposomes can be used to transfer chemicals across the blood-brain barrier); and
(b) contacting said light-absorbing particle 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 particle (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]).
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 combine the method of using a targeting ligand directed to a blood-brain barrier tight junction to result in localized transient opening of the blood brain barrier disclosed in Humphries with the method of generating nanoscale heating and photomechanical effects in vivo at the blood-brain barrier of a subject to increase the permeability of the blood brain barrier as taught by Dani.
A person of ordinary skill in the art could have combined the elements (using a targeting ligand to transiently open the blood brain barrier as disclosed in Humphries combined with administration of a light-absorbing particle comprising a ligand and applying a short pulse laser signal to generate nanoscale heating and photomechanical effects that increase the permeability of the blood brain barrier as taught by Dani) as claimed by known methods (Humphries discloses the method of using a ligand to target a blood brain barrier tight junction that results in transient opening. Dani teaches the method of administering a light-absorbing particle comprising a ligand contacting said particle with a laser to enhance permeability at the blood brain barrier tissue) with no change to the respective functions (both methods comprise directing a ligand to the blood brain barrier to aid drug delivery to the brain). Further, the combination would yield nothing more than predictable results (a targeting ligand targeting a blood brain barrier tight junction to transiently open the blood brain barrier delivered by a light-absorbing particle excited by light would be an enhanced drug delivery system to further permeate the blood brain barrier. Humphries even suggests combining its method with a method for increasing permeability of the tissue, such as Dani--again, see Humphries [0050-0052].) to one of ordinary skill in the art, thus achieving the method “of generating nanoscale heating and photomechanical effects in vivo at” the blood-brain barrier of a subject “comprising: (a) administering to said subject a light-absorbing particle, such as a plasmonic noble metal nanoparticle, wherein said light-absorbing particle comprises” the targeting ligand; and “contacting said light-absorbing particle with a short pulse laser signal, wherein absorbance of the short pulse laser signal by said light-absorbing particle results in” localized transient opening of the blood-brain barrier.
Response to Arguments
Applicant's arguments filed 12/01/25 have been fully considered but they are not persuasive.
On pages 6-7, Applicant submits that Dani fails to disclose “disrupting” the blood brain barrier and therefore the 35 U.S.C § 103 claim rejections of claims 1-5, 8-22, and 24-30 under Dani in view of Maekawa should be withdrawn. The examiner is not persuaded by this argument and maintains the 35 U.S.C. § 103 claim rejections.
Firstly, the breadth of the claims is not as argued by applicant. Applicant appears to argue that “disrupt”ing the blood brain barrier cannot be equated to a “receptor-mediated transcytosis.” In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a specific kind of mechanism for disrupting the blood brain barrier) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The only recitation related to any “disrupt”ing in claims 1and 16 is the last clause “wherein absorbance of the short pulse laser signal by said light-absorbing particle results in localized disruption of the blood-brain barrier.” Therefore, the claim requires that localized disruption (such as increasing the permeability of the blood brain barrier) occurs with absorbance of the short pulse laser signal by said light-absorbing particle (see Dani [0074-0075]: trojan horse liposome transfer ACROSS the blood brain barrier to deliver the drug and therefore an increased permeability of the blood brain barrier or “localized disruption” is achieved). Therefore, the examiner was not persuaded by this argument and has maintained the 35 U.S.C. § 103 claim rejections under Dani in view of Maekawa.
Next, on page 7, Applicant submits that the definition of “disrupt” in the current Application’s specification is different than the definition of “disrupt” in Dani and therefore the 35 U.S.C § 103 claim rejections fail to meet the claimed limitation of “disrupt”. The examiner is not persuaded by this argument and maintains that the definition of “disrupt” in Dani aligns with the definition of “disrupt” as presented by Applicant in the specification. The examiner maintains that “disrupt” as presented in Applicant’s specification is an increase in permeability of the blood-brain barrier (see [0002]: “optically exciting light-absorbing particles to locally disrupt BBB tight junctions, permitting drugs to pass into the brain.”). Therefore, a disruption of the BBB tight junctions, as defined by Applicant, results in drugs being able to pass into the brain when the drug would have, previously, had difficulty moving across the barrier. Thus, Dani discloses “disruption” of the BBB such that drugs are permitted to pass into the brain (see claim rejections of at least claims 1 and 16), that aligns with Applicant definition. Again, as presented in the advisory action mailed 12/06/24, Applicant only defines ‘disruption’ as increasing the permeability of the blood brain barrier/aiding in transport mechanism as summarized below:
Current Application’s [0002] as quoted above
[0004]: disruption is to enhance concentration of therapeutic drugs into brain
[0058]: disruption will temporarily compromise the blood-brain barrier (compromise merely means to weaken the current function—see merriam-webster dictionary. A “compromised” barrier can reasonably be achieved by increasing permeability via transport mechanisms),
[0137]: disrupt tight junction for temporary permeability increase of blood brain barrier.
Thus, the examiner maintains the interpretation of “disrupt” as an increase in permeability of the blood brain barrier is in alignment with Applicant definition and therefore the applied art, Dani, also teaches the limitation in alignment with the specification.
Further, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a specific kind of “disruption” of the blood-brain barrier) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Thus, the examiner is not persuaded by this argument and maintains the 35 U.S.C. § 103 claim rejections.
On page 8-9, Applicant submits a separate definition of “disrupt” from an outside source, Daneman. However, the claims are given the broadest reasonable interpretation in view of Application specification and therefore outside source definitions are not read into the claim language. Further, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a specific kind of “disruption” of the blood-brain barrier) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Thus, the examiner is not persuaded by this argument and maintains the 35 U.S.C. § 103 claim rejections.
On page 9, Applicant argues that the disruption disclosed in Dani does not exclusively “attack” the BBB itself. The examiner is not persuaded by this argument and maintains the 35 U.S.C. § 103 claim rejections.
First, the breadth of the claims is not as argued by Applicant. Claims 1 and 16 recite “wherein said light-absorbing particle comprises a targeting ligand that directs said light-absorbing particle to a blood-brain barrier tight junction, JAM-A, Claudin-5, ZO-1, or transferrin;”. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., attacking a blood-brain barrier) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The claim language only requires that the targeting ligand is “directed…to” one of the junctions cited.
To continue, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The combination of Dani in view of Maekawa teaches targeting to one of the junctions as cited and therefore the combination meets the claim.
Thus, the examiner is not persuaded by this argument and maintains the 35 U.S.C. § 103 claim rejections.
On page 9, Applicant submits that Dani in view of Maekawa would render the device of Dani inoperable for the principle operation. However, the examiner is not persuaded by this argument and maintains the 35 U.S.C. § 103 claim rejections under Dani in view of Maekawa. Dani teaches that the blood brain barrier is difficult to cross (see [0074-0075]) and that liposomes, including ligands (see [0049] and [0033]) are effective in aiding the BBB crossing. Therefore, combining Dani’s method of administering light to a liposome embedded with a ligand to aid in delivery across a BBB with a specific ligand as taught in Maekawa does not depart from the invention scope disclosed by Dani. Therefore, regardless of the exact transport mechanisms used in Dani and/or Maekawa, the combination of Dani in view of Maekawa results in superior delivery to the BBB that is already suggested by Dani. Thus, the combination would not destroy the principle operation of Dani as argued by Applicant. Thus, the examiner is not persuaded by this argument and maintains the 35 U.S.C. § 103 claim rejections.
Lastly on page 9, Applicant argues that Dani in view of Maekawa does not teach physical disruption of “opening of the BBB”. Again, the limitation as argued does not align with the breadth of the claims. No physical “opening” of the blood-brain barrier is recited in claims 1 or 16. See further explanation responding to this argument presented in the previous paragraphs.
Applicant continues this argument on page 10 that the current invention teaches “transient opening” of the BBB and therefore Dani does not meet the claim language. Again this “transient opening” recitation is not in claim 1 and 16. In regard to new claim 31 that positively recites “transient opening”, this argument is moot because a new 35 U.S.C. § 103 claim rejection under Humphries in view of Dani was applied to meet the new recitation of the “transient opening” of the blood-brain barrier. Thus, the examiner is not persuaded by this argument and maintains the 35 U.S.C. § 103 claim rejections.
On page 10-11, Applicant again submits a separate definition of “disrupt” from Daneman. See the examiner’s response to this argument as presented in the above paragraphs.
On page 11, Applicant submits that Dani in view of Maekawa would render the device of Dani inoperable for the principle operation. See the examiner’s response to this argument as presented in the above paragraphs.
Thus, the examiner was not persuaded by the arguments presented in the Remarks filed 12/01/25 and maintains the 35 U.S.C. § 103 claim rejections. No further arguments were made and therefore all subsequent depending claim rejections are also maintained by the examiner.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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 FARRELL/Examiner, Art Unit 3783
/MICHAEL J TSAI/Supervisory Patent Examiner, Art Unit 3783