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 Arguments
Applicant’s arguments, see pg. 5, filed 15 Dec 2025, with respect to the claim objections have been fully considered and are persuasive. The claim objections of 17 Jun 2025 have been withdrawn in view of the amended claims.
Applicant’s arguments, see pg. 5, filed 15 Dec 2025, with respect to the 35 U.S.C. 112(a) rejections have been fully considered and are persuasive. The 35 U.S.C. 112(a) rejections of 17 Jun 2025 have been withdrawn in view of the amended claims.
Applicant’s arguments, see pg. 6, filed 15 Dec 2025, with respect to the 35 U.S.C. 112(b) rejections have been fully considered and are not persuasive. The 35 U.S.C. 112(b) rejections of 17 Jun 2025 have been withdrawn in view of the amended and cancelled claims.
Applicant’s arguments, see pg. 6-12, filed 15 Dec 2025 with respect to the 35 U.S.C. 103 rejections have been considered but are moot because the new ground of rejection does not rely on the prior rejection of record for any teaching or matter specifically challenged in the argument. For a clarity of record, however, Examiner notes that the independent claims 1 and 13 currently each recites a method comprising (an open ending) steps of intrathecal administration and application of transcranial ultrasound without reciting any relationship between the two steps. See MPEP 211.03.I. Additionally, Examiner notes that a review of the original specification discloses applying transcranial ultrasound at a mechanical index ranging from 0.1 to 1.9 for a period ranging from 1 minutes to 30 minutes without any criticality for the claimed ranges of mechanical index and period (see [0030] of the original specification of the instant application).
Status of Claims
Claims 1-2, 6, 10-11, 13-15, and 18-21 are currently under examination. Claims 5, 12, and 16-17 have been cancelled since the Non-Final Office Action of 17 Jun 2025.
Declaration of 15 Dec 2025
Declaration under 37 CFR 1.132 filed 15 Dec 2025 has been fully considered but are mott because the new ground of rejections is hereby being presented in view of the amended claims.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 6, 10-11, 13-15, and 18-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites the limitation “administering intrathecally the agent in absence of a carrier comprising vesicles or microbubbles to a subject”. A review of the original specification does not explicitly disclose intrathecally administering an agent in absence of a carrier comprising vesicles or microbubbles. In particular, [0019], [0077], [0081]-[0082], and [0088] disclose the agent being IRDye8000w of 1 kDa or Panitumumab-IRDye800 of 150 kDa, but nowhere in the original specification explicitly discloses that the agent is absent of a carrier comprising vesicles or microbubbles. A broadest reasonable interpretation has been previously given to “carrier” to include a liquid in which the agent is diluted (see [0088] of the original specification), but in view of the new recitation “a carrier comprising vesicles or microbubbles”, the original specification does not explicitly disclose that the agent is absent of “a carrier comprising vesicles or microbubbles”. See MPEP 2173.05(i). Therefore, the limitation introduces new matter. Claims 2, 6, and 10-11 inherit the deficiency by the nature of their dependency on claim 1.
Claim 1 recites the limitation “applying transcranial ultrasound to the subject at a mechanical index ranging from 0.2 to 0.5 for a period of time from 10 minutes to 15 minutes”. A review of the original specification only discloses a single working example of applying transcranial ultrasound at a mechanical index of 0.25 for a period of 10 minutes (see [0017], [0020], [0022], [0075], [0078], [0081], [0087]-[0088], [0092] – which all disclose just a mechanical index of 0.25 for a period of 10 minutes). The original specification does not disclose any working examples at the claimed mechanical indices at the claimed period other than the mechanical index of 0.25 and the period of 10 minutes. Therefore, the limitation lacks scope of written description. Claims 2, 6, and 10-11 inherit the deficiency by the nature of their dependency on claim 1.
Claim 13 recites the limitation “intrathecally administering the protein in absence of a carrier comprising vesicles or microbubbles to a subject”. A review of the original specification does not explicitly disclose intrathecally administering an agent in absence of a carrier comprising vesicles or microbubbles. In particular, [0019], [0077], [0081]-[0082], and [0088] disclose the agent being IRDye8000w of 1 kDa or Panitumumab-IRDye800 of 150 kDa, but nowhere in the original specification explicitly discloses that the agent is absent of a carrier comprising vesicles or microbubbles. A broadest reasonable interpretation has been previously given to “carrier” to include a liquid in which the agent is diluted (see [0088] of the original specification), but in view of the new recitation “a carrier comprising vesicles or microbubbles”, the original specification does not explicitly disclose that the agent is absent of “a carrier comprising vesicles or microbubbles”. See MPEP 2173.05(i). Therefore, the limitation introduces new matter. Claims 14-15 and 18-21 inherit the deficiency by the nature of their dependency on claim 13.
Claim 13 recites the limitation “applying transcranial ultrasound to the subject at a mechanical index ranging from 0.2 to 0.3, for a period of time from 10 minutes to 15 minutes”. A review of the original specification only discloses a single working example of applying transcranial ultrasound at a mechanical index of 0.25 for a period of 10 minutes (see [0017], [0020], [0022], [0075], [0078], [0081], [0087]-[0088], [0092] – which all disclose just a mechanical index of 0.25 for a period of 10 minutes). The original specification does not disclose any working examples at the claimed mechanical indices at the claimed period other than the mechanical index of 0.25 and the period of 10 minutes. Therefore, the limitation lacks scope of written description Claims 14-15 and 18-21 inherit the deficiency by the nature of their dependency on claim 13.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-2, 6, 10-11, 13-15, and 18-21 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 1 recites the limitation “administering intrathecally the agent in absence of a carrier comprising vesicles or microbubbles to a subject”. The metes and bounds of the claim are unclear in view of this limitation. In particular, a negative limitation (in this case, “absence”) with an open end (“a carrier comprising vesicles or microbubbles”) fails to particularly point out and distinctly claim the agent that is intrathecally administered. See MPEP 2111.03.I. Claims 2, 6, and 10-11 inherit the deficiency by the nature of their dependency on claim 1. For purposes of the examination, the limitation is being given a broadest reasonable interpretation as “intrathecally administering the agent in absence of vesicles or microbubbles to a subject”.
Claim 13 recites the limitation “intrathecally administering the protein in absence of a carrier comprising vesicles or microbubbles to a subject”. The metes and bounds of the claim are unclear in view of this limitation. In particular, a negative limitation (in this case, “absence”) with an open end (“a carrier comprising vesicles or microbubbles”) fails to particularly point out and distinctly claim the agent that is intrathecally administered. See MPEP 2111.03.I. Claims 14-15 and 18-21 inherit the deficiency by the nature of their dependency on claim 13. For purposes of the examination, the limitation is being given a broadest reasonable interpretation as “intrathecally administering the protein in absence of vesicles or microbubbles to a subject”.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 6, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Wostyn (US PG Pub No. 2018/0228970) in view of Hersh et al. (Hersh et al. (2018) MR-guided transcranial focused ultrasound safely enhances interstitial dispersion of large polymeric nanoparticles in the living brain. PLoS ONE13(2): e0192240. https://doi.org/10.1371/journal.pone.0192240. A copy attached to this Office Action.) – hereinafter referred to as Hersh – and Chu et al. (Chu et al. Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging. Sci Rep 6, 33264 (2016). https://doi.org/10.1038/srep33264. A copy attached to this Office Action.) – hereinafter referred to as Chu.
Regarding claim 1, Wostyn discloses a method of delivering an agent to a brain ([0022]: artificial CSF or CSF-like solutions containing therapeutic agents to the intrathecal space or subarachnoid space or the cerebral ventricles of said patient), the method comprising:
administering intrathecally the agent in absence of vesicles or microbubbles to a subject ([0064]: intrathecal administration of CSF or a CSF-like solution comprising one or therapeutic agents), wherein the agent has a molecular weight ranging from 1 kDa to 150 kDa ([0064]-[0065]: therapeutic agents include transthyretin (“TTR”; 55 kDa), Cystatin C (“CysC”; 13 kDa), beta-trace (23.5-31 kDa)).
It is noted that transthyretin, Cystatin C, and beta-trace are well known in the art to be proteins and have a molecular weight of 55 kDa, 13 kDa, and 23.5-31 kDa, respectively. See previously provided evidence of Buxbaum et al. (Buxbaum et al. Transthyretin: the servant of many masters. Cell Mol Life Sci. 2009 Oct;66(19):3095-101. doi: 10.1007/s00018-009-0109-0.); Chew et al. (Chew et al. Cystatin C--a paradigm of evidence based laboratory medicine. Clin Biochem Rev. 2008 May;29(2):47-62. PMID: 18787643; PMCID: PMC2533150.); and Hoffmann et al. (Hoffmann et al. Purification and chemical characterization of beta-trace protein from human cerebrospinal fluid: its identification as prostaglandin D synthase. J Neurochem. 1993 Aug;61(2):451-6. doi: 10.1111/j.1471-4159.1993.tb02145.x.), respectively, in the Non-Final Office Action of 17 Jun 2025.
Wostyn does not disclose:
applying transcranial ultrasound to the subject at a mechanical index ranging from 0.2 to 0.5, for a period of time from 10 minutes to 15 minutes;
wherein the intrathecally administered agent is transported into central nervous system (CNS) parenchyma interstitial fluid, and brain parenchyma penetration is increased by 60% to 110% compared to a control.
Hersh, however, in the same field of endeavor in increasing interstitial fluid concentration teaches:
applying transcranial ultrasound to the subject to increase interstitial fluid concentration (Fig. 1 and pg. 3-4: Transcranial MRgFUS exposures: non-invasive FUS (focused ultrasound) exposures were applied to safely provide targeted FUS exposures to the rodent brain for increasing interstitial fluid concentration).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Wostyn’s method to include Hersh’s method of applying transcranial ultrasound. The combination would have yielded a reasonable expectation of success, since Wostyn and Hersh are directed to delivering an agent to a brain. The motivation for the combination would have been because “transcranial ultrasound can safely and effectively modulate the brain interstitium and increase the dispersion of large therapeutic entities such as particulate drug carriers or modified viruses”, as taught by Hersh (Abstract).
Fisher also in the same field of endeavor in applying transcranial ultrasound for brain penetration teaches:
applying transcranial ultrasound to the subject at a mechanical index at 0.41 for a period for 1.5 minutes (Fig. 1-2 and pg. 2: Results: tested FUS with different combinations of exposure frequency (either 0.4 or 1 MHz) and pressure (0.25–0.83 MPa) to produce exposure level in the range of 0.41–1.12 when gauged by MI, and 0.43–1.77 when gauged by CI. Animals received a single FUS exposure (10 ms bursts length, 1 Hz pulse pulse-repetition frequency, 90 s exposure duration, 0.2 mL/kg SonoVue®)).
As noted above in the Response to Arguments, a review of the original specification discloses applying transcranial ultrasound at a mechanical index ranging from 0.1 to 1.9 for a period ranging from 1 minutes to 30 minutes without any criticality for the claimed ranges of mechanical index and period (see [0030] of the original specification of the instant application). Fisher discloses applying transcranial ultrasound within the ranges for mechanical index and period disclosed in the original specification of the instant application, and even at the claimed mechanical index between 0.2 and 0.5, without any unexcepted failure (i.e., any catastrophic brain damage). Thus, while Fisher does not disclose applying the transcranial ultrasound at the disclosed range of period to increase interstitial fluid concentration, it would still be obvious to ordinary skill in the art to modify Hersh’s application of transcranial ultrasound to increase interstitial fluid concentration to Applicant’s disclosed ranges of mechanical index and period, as well as the claimed ranges, through the use of routine experimentation to “facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS (central nervous system) drug delivery” (see Abstract of Fisher). A person of ordinary skill in the art undertaking such experimentation would have had a reasonable expectation of success and the results would have been predictable.
Furthermore, the limitation “wherein the intrathecally administered agent is transported into central nervous system (CNS) parenchyma interstitial fluid” recites an intended result of intrathecally administering an agent, and the limitation “brain parenchyma penetration is increased by 60% to 110% compared to a control” also recites an intended result of the claimed method of claim 1: intended result of the claimed method is given a limited patentable weight. In particular, it is well known in the art that an intrathecal administration of an agent introduces the agent into cerebrospinal fluid, and the cerebrospinal fluid is well known in the art to be a CNS parenchyma interstitial fluid.
Regarding claim 6, Wostyn in view of Hersh and Fisher discloses all limitations of claim 1, as discussed above, and Hersh teaches (also see claim 1 above):
wherein the transcranial ultrasound comprises transcranial focused ultrasound (Fig. 1 and pg. 3-4: Transcranial MRgFUS exposures: non-invasive FUS (focused ultrasound) exposures were applied to safely provide targeted FUS exposures to the rodent brain for increasing interstitial fluid concentration).
Regarding claim 13, Wostyn discloses a method of delivering a protein to a brain ([0022]: artificial CSF or CSF-like solutions containing therapeutic agents to flow towards the brain; [0064]-[0065]: therapeutic agents include transthyretin (“TTR”), Cystatin C (“CysC”), beta-trace; [0034]: for treatment of neurological disorders), the method comprising:
intrathecally administering the protein in absence of vesicles or microbubbles to a subject ([0064]: intrathecal administration of CSF or a CSF-like solution comprising one or therapeutic agents), wherein the agent has a molecular weight ranging from 1 kDa to 150 kDa ([0064]-[0065]: therapeutic agents include transthyretin (“TTR”; 55 kDa), Cystatin C (“CysC”; 13 kDa), beta-trace (23.5-31 kDa)).
It is noted that transthyretin, Cystatin C, and beta-trace are well known in the art to be proteins and have a molecular weight of 55 kDa, 13 kDa, and 23.5-31 kDa, respectively. See previously provided evidence of Buxbaum et al. (Buxbaum et al. Transthyretin: the servant of many masters. Cell Mol Life Sci. 2009 Oct;66(19):3095-101. doi: 10.1007/s00018-009-0109-0.); Chew et al. (Chew et al. Cystatin C--a paradigm of evidence based laboratory medicine. Clin Biochem Rev. 2008 May;29(2):47-62. PMID: 18787643; PMCID: PMC2533150.); and Hoffmann et al. (Hoffmann et al. Purification and chemical characterization of beta-trace protein from human cerebrospinal fluid: its identification as prostaglandin D synthase. J Neurochem. 1993 Aug;61(2):451-6. doi: 10.1111/j.1471-4159.1993.tb02145.x.), respectively, in the Non-Final Office Action of 17 Jun 2025.
Wostyn does not disclose:
applying transcranial ultrasound to the subject at a mechanical index ranging from 0.2 to 0.3, for a period of time from 10 minutes to 15 minutes;
wherein the intrathecally administered protein is transported into central nervous system (CNS) parenchyma interstitial fluid, and brain parenchyma penetration is increased by 60% to 110% compared to a control.
Hersh, however, in the same field of endeavor in increasing interstitial fluid concentration teaches:
applying transcranial ultrasound to the subject to increase interstitial fluid concentration (Fig. 1 and pg. 3-4: Transcranial MRgFUS exposures: non-invasive FUS (focused ultrasound) exposures were applied to safely provide targeted FUS exposures to the rodent brain for increasing interstitial fluid concentration).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Wostyn’s method to include Hersh’s method of applying transcranial ultrasound. The combination would have yielded a reasonable expectation of success, since Wostyn and Hersh are directed to delivering an agent to a brain. The motivation for the combination would have been because “transcranial ultrasound can safely and effectively modulate the brain interstitium and increase the dispersion of large therapeutic entities such as particulate drug carriers or modified viruses”, as taught by Hersh (Abstract).
Fisher also in the same field of endeavor in applying transcranial ultrasound for brain penetration teaches:
applying transcranial ultrasound to the subject at a mechanical index ranging from 0.41 to 1.12 for a period for 1.5 minutes (Fig. 1-2 and pg. 2: Results: tested FUS with different combinations of exposure frequency (either 0.4 or 1 MHz) and pressure (0.25–0.83 MPa) to produce exposure level in the range of 0.41–1.12 when gauged by MI, and 0.43–1.77 when gauged by CI. Animals received a single FUS exposure (10 ms bursts length, 1 Hz pulse pulse-repetition frequency, 90 s exposure duration, 0.2 mL/kg SonoVue®)).
As noted above in the Response to Arguments, a review of the original specification discloses applying transcranial ultrasound at a mechanical index ranging from 0.1 to 1.9 for a period ranging from 1 minutes to 30 minutes without any criticality for the claimed ranges of mechanical index and period (see [0030] of the original specification of the instant application). Fisher discloses applying transcranial ultrasound within the ranges for mechanical index and period disclosed in the original specification of the instant application without any unexcepted failure (i.e., any catastrophic brain damage). Thus, while Fisher does not disclose applying the transcranial ultrasound at the disclosed ranges of mechanical index and period to increase interstitial fluid concentration, it would still be obvious to ordinary skill in the art to modify Hersh’s application of transcranial ultrasound to increase interstitial fluid concentration to Applicant’s disclosed ranges of mechanical index and period, as well as the claimed ranges, through the use of routine experimentation to “facilitate the design toward using focused ultrasound as a safe and reliable noninvasive CNS (central nervous system) drug delivery” (see Abstract of Fisher). A person of ordinary skill in the art undertaking such experimentation would have had a reasonable expectation of success and the results would have been predictable.
Furthermore, the limitation “wherein the intrathecally administered protein is transported into central nervous system (CNS) parenchyma interstitial fluid” recites an intended result of intrathecally administering a protein, and the limitation “brain parenchyma penetration is increased by 60% to 110% compared to a control” also recites an intended result of the claimed method of claim 13: intended result of the claimed method is given a limited patentable weight. In particular, it is well known in the art that an intrathecal administration of any agent introduces the agent into cerebrospinal fluid, and the cerebrospinal fluid is well known in the art to be a CNS parenchyma interstitial fluid.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Wostyn in view of Hersh and Fisher, as applied to claim 1 above, and further in view of Sadik et al. (US PG Pub No. 2023/0149684, a priority date of 01 Apr 2020) – hereinafter referred to as Sadik.
Regarding claim 2, Wostyn in view of Hersh and Fisher discloses all limitations of claim 1, as discussed above, and Wostyn in view of Hersh and Fisher does not disclose:
applying the transcranial ultrasound across the whole brain of the subject
Sadik, however, in the same field of endeavor in applying transcranial ultrasound for brain penetration teaches:
applying transcranial ultrasound across the whole brain of the subject (Fig. 3-4 and [0072]: emitting focused ultrasound onto at least one site of the brain of said subject with said device, preferentially over the entire brain tissue).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Wostyn’s method to include Sadik’s method of applying transcranial ultrasound across the whole brain. The combination would have yielded a reasonable expectation of success, since Wostyn and Sadik are directed to delivering an agent to a brain. The motivation for the combination would have been to ensure effective application of transcranial ultrasound by targeting the interstitial fluid across the whole brain and “improving bioavailability in at least one region of the tissue” ([0072] of Sadik).
Claims 10-11 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Wostyn in view of Hersh and Fisher, as applied to claims 1 and 13, respectively above, and further in view of Chen (US PG Pub No. 2021/0228498, a priority date of 07 Feb 2019).
Regarding claim 10, Wostyn in view of Hersh and Fisher discloses all limitations of claim 1, as discussed above, and Wostyn does not disclose:
wherein the agent is an antibody or fragment thereof.
Chen, however, in the same field of delivering an agent to a brain teaches:
an agent is an antibody or fragment thereof ([0103]: therapeutic antibody includes Panitumumab).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Wostyn’s method to include Chen’s method of intrathecally administering panitumumab. The combination would have yielded a reasonable expectation of success, since Wostyn and Chen are both directed to delivering an agent to a brain to treat a brain condition. The motivation for the combination would have been to deliver a therapeutic agent to the brain to treat malignant glioma ([0005] of Chen).
Regarding claim 11, Wostyn in view of Hersh and Fisher discloses all limitations of claim 1, as discussed above, and Wostyn does not disclose:
wherein the agent is a nucleic acid.
Chen, however, in the same field of delivering an agent to a brain teaches:
delivering a nucleic acid ( [0070]: chimeric receptor (e.g., a nucleic acid encoding chimeric receptor) introduced into an immune cell, which is administered to the subject).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Wostyn’s method to include Chen’s method of intrathecally administering a nucleic acid. The combination would have yielded a reasonable expectation of success, since Wostyn and Chen are both directed to delivering an agent to a brain to treat a brain condition. The motivation for the combination would have been to target brain cancer cells using immunotherapy ([0068] of Chen).
Regarding claims 14-15, Wostyn in view of Hersh and Fisher discloses all limitations of claim 13, as discussed above, and Wostyn does not disclose:
wherein the protein is an antibody (claims 14-15); and
wherein the antibody is panitumumab (claim 15).
Chen, however, in the same field of delivering an agent to a brain teaches:
intrathecally administering a protein ([0118]: intrathecally administer therapeutic agents), wherein the protein is an antibody ([0103]: therapeutic antibody includes Panitumumab), and
wherein the antibody is panitumumab ([0103]: therapeutic antibody includes Panitumumab).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Wostyn’s method to include Chen’s method of intrathecally administering panitumumab. The combination would have yielded a reasonable expectation of success, since Wostyn and Chen are both directed to delivering an agent to a brain to treat a brain condition. The motivation for the combination would have been to deliver a therapeutic agent to the brain to treat malignant glioma ([0005] of Chen).
Claims 18-21 are rejected under 35 U.S.C. 103 as being unpatentable over Wostyn in view of Hersh and Fisher, as applied to claim 13 above, and further in view of Fukuda et al. (US PG Pub No. 2019/0175684) – hereinafter referred to as Fukuda.
Regarding claim 18, Wostyn in view of Hersh and Fisher discloses all limitations of claim 13, as discussed above, and Wostyn does not disclose:
wherein the protein comprises an imaging agent selected from fluorescent molecules, radioisotopes, nucleotide chromophores, chemiluminescent moieties, magnetic particles, and bioluminescent moieties.
Fukuda, however, in the same field of delivering a protein to a brain teaches:
a protein comprising an imaging agent selected from fluorescent molecules, radioisotopes, nucleotide chromophores, chemiluminescent moieties, magnetic particles, and bioluminescent moieties ([0067]: conjugate bound with peptide; [0079]-[0083]: conjugate containing detectable substance, for example, a radioisotope, an enhancing agent for MRI (e.g., paramagnetic ions), a radiopaque substance, a contrast agent, a fluorescent substance, or the like).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Wostyn’s method to include Fukuda’s method of delivering a protein containing an imaging agent to a brain. The combination would have yielded a reasonable expectation of success, since Wostyn and Fukuda are both directed to delivering a protein to a brain to treat a brain condition. The motivation for the combination would have been to “enable[s] detection of the conjugate of the present invention (or the protein intended to be delivered to a brain) in vivo directly or indirectly using an appropriate visualization or imaging means”, as taught by Fukuda ([0079]).
Regarding claims 19-21, Wostyn in view of Hersh and Fisher discloses all limitations of claim 13, as discussed above, and Wostyn does not disclose:
wherein the protein comprises a fluorescent dye (claims 19-21);
wherein the protein is an antibody (claims 20-21); and
wherein the antibody is panitumumab (claim 21).
Fukuda, however, in the same field of delivering a protein to a brain teaches:
panitumumab comprising a fluorescent dye ([0067]-[0077]: conjugate bound with peptide, wherein the conjugate is an anticancer agent, such as panitumumab (Vectibix); [0079]-[0083]: conjugate containing detectable substance, for example, a radioisotope, an enhancing agent for MRI (e.g., paramagnetic ions), a radiopaque substance, a contrast agent, a fluorescent substance, or the like).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Wostyn’s method to include Fukuda’s method of delivering a protein containing an imaging agent to a brain. The combination would have yielded a reasonable expectation of success, since Wostyn and Fukuda are both directed to delivering a protein to a brain to treat a brain condition. The motivation for the combination would have been to “target[ed] to malignant tumor (in the brain) by the action of the part corresponding to the peptide of the present invention, preferred examples of the functionality include anti-cancer activity and provision of detectability”, as taught by Fukuda ([0069]).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mano et al. (Mano et al. (2016). Intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain. Journal of Neurosurgery, 124(5), 1490-1500. https://doi.org/10.3171/2015.3.JNS142152. A copy attached to this Office Action.) discloses applying transcranial ultrasound to parenchyma (see at least Abstract).
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 Younhee Choi whose telephone number is (571)272-7013. The examiner can normally be reached M-F 9AM-5PM EST.
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/Y.C./Examiner, Art Unit 3797
/ANH TUAN T NGUYEN/Supervisory Patent Examiner, Art Unit 3795
3/23/26