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 .
Election/Restrictions
Applicant’s election without traverse of group I (claims 1-2, 4, 7, 11, 20, 29, 32, 34, 49, 55-56 and 62) in the reply filed on 08/15/2025 is acknowledged. Claims 67-68, 70, 75-76, 78 and 84 are withdrawn.
Claim Objections
Claim 1 is objected to because of the following informalities: the abbreviated term “Her2+” in line 1 should be defined in its first occurrence in claim 1.
Claim 1 is objected to because of the following informalities: the claim limitation “the brain” in line 1 should be amended to recite “a brain”.
Claim 1 is objected to because of the following informalities: the claim limitation “the human patient” in line 5 should be amended to recite “the selected human patient”.
Claim 1 is objected to because of the following informalities: the claim limitation “the cranium” in line 5 should be amended to recite “a cranium”.
Claim 1 is objected to because of the following informalities: the claim limitation “the blood-brain barrier...” in line 6 should be amended to recite “a blood-brain barrier”.
Claim 11 is objected to because of the following informalities: the claim limitation “the human patient” in line 2 should be amended to recite “the selected human patient”.
Claim 20 is objected to because of the following informalities: the claim limitations “the frontal lobe”, “the supratentorial region”, “the infratentorial region”, “the insula”, “the brainstem”, “the pons”, “the posterior fossa” in lines 3-5 should be amended to recite “a frontal lobe”, “a supratentorial region”, “a infratentorial region”, “a insula”, “a brainstem”, “a pons”, “a posterior fossa”
Claim 20 is objected to because of the following informalities: the claim limitations “one or more of the frontal lobe” in line 3 should be amended to recite “one or more of frontal lobe”.
Claim 49 is objected to because of the following informalities: the claim limitation “the patient” in line 5 and 7 should be amended to recite “the selected human patient”.
Claim 56 is objected to because of the following informalities: the claim is missing a “;” after “the tumors do not substantially increase in size after completion of the method” in line 4.
Claim 49 is objected to because of the following informalities: the claim limitation “...6 the SUVs are normalized to an appropriate control region’s mean SUV” in line 12 should read “the SUVs are normalized to an appropriate control region’s mean SUV”.
Claim 62 is objected to because of the following informalities: the claim limitation “the effect” in line 4 should be amended to recite “an effect”.
Claim 62 is objected to because of the following informalities: the claim limitation “the effect” in line 7 should be amended to recite “an effect”.
Claim 62 is objected to because of the following informalities: the abbreviated terms “MRgFUS” in line 7, “SPECT/CT” in line 9, and “MRI in line 10 should be defined in its first occurrence in claim 62.
Claim 62 is objected to because of the following informalities: the claim limitation “MRgFUS BBB treatment” in line 18 should be amended to read “MRgFUS, BBB treatment”.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 4, 7, 11, 20, 29, 32, 34, 49, 55-56 and 62 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.
Regarding claim 1, the claim limitation “Her2+” in lines 3 and 4 is indefinite because it is unclear if these Her2+ is same as the Her2+ that is already recited in line 1.
Regarding claim 2, the claim limitation “...optionally a focused, magnetic resonance-guided ultrasound beam (MRgFUS)” in line 6 is indefinite because it is unclear if this claim limitation after the term “optionally” is part of the claim and further limits the claim. The examiner advised the application to delete the term “optionally”.
Regarding claim 7, the claim limitation “a plurality of lesions” in line 4 is indefinite because it is unclear if these plurality of lesions same as the plurality of lesions that is already recited in line 3.
Regarding claim 7, the claim limitation “a plurality of post-resection cavities” in lines 7-8 is indefinite because it is unclear if these plurality of post-resection cavities same as the plurality of post-resection cavities that is already recited in lines 5-6.
Regarding claim 11, the claim limitation “the focus ultrasound beam” in line 2 is indefinite because it is unclear what focus ultrasound beam the claim is referring to since claim 1 does not limit to any focus ultrasound beam.
Regarding claim 11, claim recites the limitation "the treatment duration" in lines 5. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 11, The terms “about” recited throughout in lines 4-23 are relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the term “about” renders the claim indefinite.
Regarding claim 20, the claim limitation “the focus ultrasound beam” in line 2 is indefinite because it is unclear what focus ultrasound beam the claim is referring to since claim 1 does not limit to any focus ultrasound beam.
Regarding claim 32, the claim limitations “...optionally wherein the trastuzumab is administered at a dose of about 6 mg/kg to about 8mg/kg...and/or administered by systemic infusion” in lines 3-14 are indefinite because it is unclear if the claim limitations after the term “optionally” are part of the claim and further limits the claim. The examiner advised the application to delete the term “optionally”.
Regarding claim 32, The terms “about” recited throughout in lines 3-8 are relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the term “about” renders the claim indefinite.
Regarding claim 34, the claim limitations “...optionally selected from ibritumomab tiuxetan, Obinutuzumab, ofatumumab, and rituximab...optionally daratumumab” in lines 21-34 are indefinite because it is unclear if the claim limitations after the term “optionally” are part of the claim and further limits the claim. The examiner advised the application to delete the term “optionally”.
Regarding claim 56, the claim limitations “the tumors” in lines 4-6 are indefinite because it is unclear what tumors that claim is referring to since claim 1 does not limit plurality of tumors.
Regarding claim 62, claim recites the limitation "the transit" and “the treatment agent” in lines 2-3, "the imaging tracer signal" in lines 8-9, “the standardized uptake value ratios (SUVRS) in lines 13-14, and “the entire tumor volume” in line 14. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 62, the claim limitation “...optionally comprises indium-111” in line 3 is indefinite because it is unclear if this claim limitation after the term “optionally” is part of the claim and further limits the claim. The examiner advised the application to delete the term “optionally”.
Regarding claim 62, the claim limitation “the therapeutic deliver” in line 4 is indefinite because it is unclear what therapeutic delivery the claim is referring to since claim 1 does not explicitly recite therapeutic delivery.
Regarding claim 62, the claim limitations “...optionally MRgFUS, BBB treatment on therapeutic delivery...to characterize the effect of MRgFUS, BBB treatment on improving the therapeutic deliver across the entire target region of the tumor volume” in lines 6-18 are indefinite because it is unclear if the claim limitations after the term “optionally” are part of the claim and further limits the claim. The examiner advised the application to delete the term “optionally”.
Regarding claim 62, the claim limitations “the target tumor regions” in line 11 is indefinite because it is unclear what target tumor regions that claim is referring to since claim 1 does not limit any target tumor regions.
Regarding claim 62, the claim limitations “the entire target” and “the tumor volume” in line 19 is indefinite because it is unclear what the entire target region the claim is referring to. Furthermore, the claim limitation “the tumor volume” is indefinite because it is unclear if this tumor volume is referring to “the entire tumor volume” recited in line 14.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 2, 4, 7, 11, 29, 32, 49, 55, and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (“Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model”; Journal of Controlled release 163 (2012); hereinafter Park), in view of Leuthardt et al. (US 2019/0323086; hereinafter Leuthardt).
Regarding claim 1, Park discloses ultrasound mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model. Park shows a method of treating a Her2+ metastatic breast tumor in the brain (see abstract), comprising:(a) selecting a patient having a Her2+ metastatic breast tumor in the brain (see abstract, “introduction” on page 277, and “material and methods” on page 278) and (b) applying an ultrasound beam to the cranium of the patient to cause transient disruption of the blood-brain barrier (BBB) of the selected patient (see “material and methods” on page 278, “ultrasound” on page 279; fig. 2), wherein, the selected patient is receiving: one or more antibodies targeting Her2 during and/or after the application of the ultrasound beam (abstract states “Trastuzumab has showed positive results in many patients with metastatic HER2-positive breast cancer...” see “result” on page 280, see “discussion” on page 281); and one or more microbubble compositions immediately before and/or during the application of the ultrasound beam (see abstract; “study design” on page 278; fig. 2).
But, Park fails to explicitly state that the patient is a human.
Leuthardt discloses a methods and systems for noninvasive and localized brain treatment. Leuthardt teaches a system that can be used to treat brain tumor for mice and human (see par. [0067]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing of the claimed invention, to have utilized the teaching of having the patient being a human, in the invention of Park, as taught by Leuthardt, to be able to non-invasively treat brain tumor of a human patient.
Regarding claim 2, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the ultrasound beam is a focused beam (see abstract).
Regarding claim 4, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the application of the ultrasound beam targets at least one, or two, or three regions or sites of the brain (see fig. 2 and 4).
Regarding claim 7, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the selected human patient: presents with a plurality of lesions (see fig. 2 and 4).
Regarding claim 11, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows where the focused ultrasound beam is applied directly to the patient's cranium (see fig. 2 and 4), but Park fails to explicitly state that a helmet-shaped ultrasound transducer.
Leuthardt discloses a methods and systems for noninvasive and localized brain treatment. Leuthardt teaches using a helmet-shaped ultrasound transducer to treat human patient (see par. [0067], [0074]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing of the claimed invention, to have utilized the teaching of a helmet-shaped ultrasound transducer to treat human patient, in the invention of Park, as taught by Leuthardt, to be able to non-invasively treat brain tumor of a human patient, and the helmet provides easier remove and installation of the unit for targeting different brain regions.
Regarding claim 29, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows a full length antibody (see abstract).
Regarding claim 32, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, as best understood of indefinite claim limitation in the claim, Park shows wherein the antibody targeting Her2 is trastuzumab (see abstract).
Regarding claim 49, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein the microbubble compositions: are administered by bolus injection (see “ultrasound” on page 279).
Regarding claim 55, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein substantially all of the disrupted BBB closes after the application of the ultrasound beam (“introduction” on page 278 states transiently disrupting the BBB which means the BBB will closes after the treatment).
Regarding claim 56, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park shows wherein: the transient disruption of the BBB allows for movement of the antibody targeting Her2 across the BBB (see abstract; “study design” on page 278).
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (“Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model”; Journal of Controlled release 163 (2012); hereinafter Park), in view of Leuthardt et al. (US 2019/0323086; hereinafter Leuthardt) as applied to claim 1 above, and further in view of Peyman (US 2019/0091350).
Regarding claim 20, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore Park teaches focused ultrasound beam targets in the brain (see abstract), but fails to explicitly state wherein the focused ultrasound beam targets in temporal lobe.
Peyman discloses HIFU in brain and specially in temporal lobe for cancer treatment (see par. [0064], [0105). Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing of the claimed invention, to have utilized the teaching of focus ultrasound beam targets in temporal lobe in the invention of Park and Leuthardt, as taught by Peyman, to be able to treat cancer in temporal lobe to improve cognitive and motor functions controlled by temporal lobe.
Claim 34 is rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (“Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model”; Journal of Controlled release 163 (2012); hereinafter Park), in view of Leuthardt et al. (US 2019/0323086; hereinafter Leuthardt) as applied to claim 1 above, and further in view of Ruiz-Opaz et al. (US 2013/0177500; hereinafter Ruiz).
Regarding claim 34, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore, Park teaches administering an antibody-based anti-tumor combination agent (see abstract), but fails to explicitly state , wherein: the antibody-based anti-tumor combination agent is a full length antibody, which is a monoclonal antibody a bispecific antibody.
Ruiz discloses anti-desper inhibitors as therapeutics for inhibition of pathological angiogenesis and tumor cell invasiveness and for molecular imaging and target delivery. Ruiz teaches : the antibody-based anti-tumor combination agent is a full length antibody (see par. [0048], [03331]), which is a monoclonal antibody a bispecific antibody (see par. [0048], [03331]). Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have utilized the teaching of the antibody-based anti-tumor combination agent is a full length antibody, which is a monoclonal antibody a bispecific antibody in the invention of Park and Leuthardt, as taught by Ruiz, to provide a superior serum which contributes to a longer half-life in the body, target and destroy cancerous cells, and provide a more stable antibody.
Claim 62 is rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (“Ultrasound-mediated blood-brain/blood-tumor barrier disruption improves outcomes with trastuzumab in a breast cancer brain metastasis model”; Journal of Controlled release 163 (2012); hereinafter Park), in view of Leuthardt et al. (US 2019/0323086; hereinafter Leuthardt) as applied to claim 1 above, and further in view of Hiscock et al. (US 2016/0144062; hereinafter Hiscock).
Regarding claim 62, Park and Leuthardt disclose the invention substantially as described in the 103 rejection above, furthermore as best understood of indefinite clam language, Park shows wherein: the therapeutic delivery is quantified to determine the effect of improved therapeutic delivery across the BBB specific to the treatment agent being delivered (see abstract; see “result” on page 280, see “discussion” on page 281; fig. 3, 4, 5 and 6) and the effect of ultrasound beam (see abstract; see “result” on page 280, see “discussion” on page 281; fig. 3, 4, 5 and 6).
But, Park and Leuthardt fail to explicitly state the one or more antibodies targeting Her2 are labeled with a tracer label, to permit tracking of the transit of the treatment agent.
Hiscock discloses the uses of HER2 binders. Hiscock teaches the one or more antibodies targeting Her2 are labeled with a tracer label, to permit tracking of the transit of the treatment agent (see par. [0017], [0049]). Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing of the claimed invention, to have utilized the teaching of the one or more antibodies targeting Her2 are labeled with a tracer label, to permit tracking of the transit of the treatment agent in the invention of Park and Leuthardt, as taught by Hiscock, to be able to track, visualize and treat cancer with high precision by directly treating tumor while minizine damage to healthy tissue.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHAHDEEP MOHAMMED whose telephone number is (571)270-3134. The examiner can normally be reached Monday to Friday, 9am to 5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne M Kozak can be reached at (571)270-0552. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SHAHDEEP MOHAMMED/Primary Examiner, Art Unit 3797
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