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
This action is in response to the remarks filed on 12/24/2025.
The amendments filed on 12/24/2025 have been entered. Accordingly, claims 1-12 and 14-22 remain pending. Claim 13 is cancelled.
The objections to the claims have been withdrawn in light of the amendments and the applicant’s remarks.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6, 9-16 and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Ferreira et al (US 20140046246) in view of Krishna (US 20220233694).
Regarding claim 1, Ferreira teaches pressure-pulse tumor-priming device (“devices disclosed here is presented in Examples 5 through 8 with two clinically relevant entities: a porphyrin and a protein. Porphyrins and porphyrin derivatives are currently employed as photosensitizers in the photodynamic therapy of cancer. Their use in the treatment of skin cancers” [0031]) comprising:
- a pulsed laser system with a pulse repetition rate between 0.1 Hz and 100 Hz (“laser pulses were fired with the second harmonic of a Nd:YAG laser (532 nm, 10 Hz,” [0071]);
- a light guide configured to direct laser pulses to one or more light-to-pressure transducers (“FIG. 5 …an optical guide (7) is connected to a pulsed laser source and the distal end is directed to a thin absorbing layer (4) of a film containing a PAC reference compound. The optical guide provides directionality with or without physical contact between the laser source and the absorbing layer containing the PAC reference compound” [0040]);
- one or more light-to-pressure transducers configured to absorb laser pulses from said pulsed laser system and generate pressure pulses, wherein said pressure pulses have peak compressional pressures between 0.1 MPa and 100 MPa, and 90% of each pressure pulse lasts between 0.1 ns and 500 ns (“One laser pulse (1) may be guided and/or focused to a part of the film (4) and subsequent laser pulses may be guided to the same or to different parts of the film (4). A rigid window element (3) is transparent to the wavelength of the laser pulse (1) that is selectively absorbed by the PAC reference compound incorporated in the thin film (4)” [0040]); “rate of pressure increase per unit of time, expressed in units of bar/s or more conveniently in bar/ns. "Rise time of an acoustic transient" is defined as the time from 10% to 90% of the peak pressure” [0009]);
- a tumor-positioning support structure, configured to couple one or more light-to-pressure transducers with a selected area from a solid tumor, at a distance shorter than 3 cm from said area (“photosensitizers in the photodynamic therapy of cancer. Their use in the treatment of skin cancers and of skin disorders such as actinic keratoses, squamous cell carcinoma” [0031]; also see fig. 5 and the associated pars); and
- a control system configured to limit the exposure of said solid tumor to said pressure pulses for a period of time between 1 second and 60 minutes (“transdermal delivery of a porphyrin with molecular weight ca. 1 kDa through the skin of a minipig, with the device of Example 1 and 12 laser pulses at 355 nm with laser fluences of 10 mJ/cm.sup.2, focused to an area of 1 cm.sup.2, and an incubation time of 20 minutes” [0041]).
As seen above, it is believed that Ferreira teaches all the broad claimed limitation under broadest reasonable interpretation. Yet, in an interpretation, if one argues that Ferreira does not teach tumor priming device, Krishna reference is introduced hereinbelow in an effort to provide compact prosecution to show the teachings as well.
In the same field of endeavor, Krishna in the entirety of the document teaches similar invention to the present application. Specifically, Krishna teaches systems, kits, and methods for administering a gel composition into a tumor of a subject and treating with laser light (e.g., for photoacoustic destruction of the tumor and tumor debris generation), where the gel comprises functionalized fullerenes (FFs) and a biocompatible polymer (abst). Schematic showing how photoacoustic or mechanical destruction of tumor leads to cellular debris that provides multitude of neoantigens from heterogeneous tumor for priming of immune system [0020].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with priming tumors as taught by Krishna because it helps to overcome current treatments shortcomings and lack approaches to localize to the tumor ([0004] of Krishna).
Regarding claim 2, Ferreira teaches wherein said light guide comprises one or more optical fibers or light pipes (“wherein said optical guide (7) is preferably at least one fiber optic with the proximal end coupled to the pulsed laser source [see claim 13 of Ferreira]).
Regarding claim 3, Ferreira teaches wherein said light guide comprises mirrors, lenses, prisms, diffusers or polarizers, or any combination thereof (“The light transmitted through the film (4) is optionally reflected by a front-face mirrored support element (5” [0040]).
Regarding claim 4, Ferreira teaches wherein said light-to-pressure transducer comprises a laser light absorbing system and a material with a Grineisen parameter higher than 0.5, and wherein each pressure pulse is the wavefront of a photoacoustic wave (“the thin light-absorbing absorbing film can be fabricated with polymers with low nanosecond pulsed laser ablation thresholds. These are the guidelines to make devices that efficiently convert laser pulse energy in high intensity, short duration and broadband acoustic transients” [0024]).
Regarding claim 5, Ferreira teaches wherein said light-to-pressure transducer comprises a laser light absorbing system and a material with an ablation threshold below 200 mJ/cm2, and wherein each pressure pulse is the wavefront of a shock wave (“the thin light-absorbing absorbing film can be fabricated with polymers with low nanosecond pulsed laser ablation thresholds. These are the guidelines to make devices that efficiently convert laser pulse energy in high intensity, short duration and broadband acoustic transients” [0024]; “photoacoustic waves by thermoelastic expansion of a confined absorbing medium can be achieved at low laser fluences (below the ablation threshold that depends on the material but is typically above 50 mJ/cm.sup.2), may occur within the duration of the laser pulse (.tau..sub.L) and is non-destructive” [0011]).
Regarding claim 6, Ferreira teaches wherein said tumor-positioning support structure is configured to hold one or more light-to-pressure transducers together with an acoustic coupling element disposed between said transducers and the surface of a solid tumor (“A rigid window element (3) is transparent to the wavelength of the laser pulse (1) that is selectively absorbed by the PAC reference compound incorporated in the thin film (4). The light transmitted through the film (4) is optionally reflected by a front-face mirrored support element (5) and makes a second passage, with more absorption, through the film (4). The photoacoustic wave produced in the film (4) is optionally transmitted through the support element (5) to the biological barrier (B), such as for example skin, with the acoustic coupling favored by the dermatologic formulation (A) containing the drug to be delivered to the skin (B). Close contact between window element (3), thin film (4) and support element (5) is provided by a structural element (6). This structural element may incorporate a technology to orient the laser pulse (1) and distribute subsequent laser pulses to different parts of the film (4).” [0040]).
Regarding claim 9, Ferreira teaches wherein said tumor-positioning support structure is a catheter and the light guide is one or more optical fibers configured to carry the laser light from the light source through the catheter, to one or more light-to-pressure transducers at the distal ends of the optical fibers (“wherein said optical guide (7) is preferably at least one fiber optic with the proximal end coupled to the pulsed laser source [see claim 13 of Ferreira]; “opto-acoustic generator to generate acoustic, or ultrasound, waves from a pulsed laser-energy source [10].The absorption of a laser pulse by a graphite-containing layer applied to the tip of an optical fiber connected to the laser source was shown to efficiently produce very-wide-band acoustic pulses.” [0006]; “fiber optic and inserted in a portion of a human body to generate an acoustic radiation field in that portion.” [0005]).
Regarding claim 10, Ferreira teaches wherein the catheter is configured for insertion into a body cavity, duct, vessel, brain, skin or adipose tissue (“fiber optic and inserted in a portion of a human body to generate an acoustic radiation field in that portion.” [0005]).
Regarding claim 11, Ferreira teaches wherein the tumor-positioning support structure comprises a sharp end configured to enable the insertion of one or more light-to-pressure transducers into said solid tumor (This structural element may incorporate a technology to orient the laser pulse (1) and distribute subsequent laser pulses to different parts of the film (4).” [0040]) “fiber optic and inserted in a portion of a human body to generate an acoustic radiation field in that portion.” [0005]).
Regarding claims 12 and 22, Ferreira teaches a method for treating a solid tumor in a subject afflicted with cancer with pressure-pulse tumor-priming device (“devices disclosed here is presented in Examples 5 through 8 with two clinically relevant entities: a porphyrin and a protein. Porphyrins and porphyrin derivatives are currently employed as photosensitizers in the photodynamic therapy of cancer. Their use in the treatment of skin cancers” [0031]) comprising:
- a pulsed laser system with a pulse repetition rate between 0.1 Hz and 100 Hz (“laser pulses were fired with the second harmonic of a Nd:YAG laser (532 nm, 10 Hz,” [0071]);
- a light guide configured to direct laser pulses to one or more light-to-pressure transducers (“FIG. 5 …an optical guide (7) is connected to a pulsed laser source and the distal end is directed to a thin absorbing layer (4) of a film containing a PAC reference compound. The optical guide provides directionality with or without physical contact between the laser source and the absorbing layer containing the PAC reference compound” [0040]);
- one or more light-to-pressure transducers configured to absorb laser pulses from said pulsed laser system and generate pressure pulses, wherein said pressure pulses have peak compressional pressures between 0.1 MPa and 100 MPa, and 90% of each pressure pulse lasts between 0.1 ns and 500 ns (“One laser pulse (1) may be guided and/or focused to a part of the film (4) and subsequent laser pulses may be guided to the same or to different parts of the film (4). A rigid window element (3) is transparent to the wavelength of the laser pulse (1) that is selectively absorbed by the PAC reference compound incorporated in the thin film (4)” [0040]); “Nd:YAG laser (5-6 ns pulse width) with and energy per pulse ca. 10 mJ/cm.sup.2 at 355 nm” [0029]; “rate of pressure increase per unit of time, expressed in units of bar/s or more conveniently in bar/ns. "Rise time of an acoustic transient" is defined as the time from 10% to 90% of the peak pressure” [0009]);
- a tumor-positioning support structure, configured to couple one or more light-to-pressure transducers with a selected area from a solid tumor, at a distance shorter than 3 cm from said area (“photosensitizers in the photodynamic therapy of cancer. Their use in the treatment of skin cancers and of skin disorders such as actinic keratoses, squamous cell carcinoma” [0031]; also see fig. 5 and the associated pars); and
- a control system configured to limit the exposure of said solid tumor to said pressure pulses for a period of time between 1 second and 60 minutes (“transdermal delivery of a porphyrin with molecular weight ca. 1 kDa through the skin of a minipig, with the device of Example 1 and 12 laser pulses at 355 nm with laser fluences of 10 mJ/cm.sup.2, focused to an area of 1 cm.sup.2, and an incubation time of 20 minutes” [0041]);
- pressure-pulse tumor priming of the solid tumor by exposure of said solid tumor to one or more pressure pulses (“devices disclosed here is presented in Examples 5 through 8 with two clinically relevant entities: a porphyrin and a protein. Porphyrins and porphyrin derivatives are currently employed as photosensitizers in the photodynamic therapy of cancer. Their use in the treatment of skin cancers” [0031]), wherein said pressure pulses have peak compressional pressures between 0.1 MPa and 100 MPa, and 90% of each pressure pulse lasts between 1 ns and 500 ns (“rate of pressure increase per unit of time, expressed in units of bar/s or more conveniently in bar/ns. "Rise time of an acoustic transient" is defined as the time from 10% to 90% of the peak pressure” [0009]); and
- administering of one or more anticancer therapeutic agents to said subject, thereby treating said solid tumor in a subject afflicted with cancer (“a porphyrin and a protein. Porphyrins and porphyrin derivatives are currently employed as photosensitizers in the photodynamic therapy of cancer. Their use in the treatment of skin cancers” [0031]).
As seen above, it is believed that Ferreira teaches all the broad claimed limitation under broadest reasonable interpretation. Yet, in an interpretation, if one argues that Ferreira does not teach tumor priming device, Krishna reference is introduced hereinbelow in an effort to provide compact prosecution to show the teachings as well.
In the same field of endeavor, Krishna in the entirety of the document teaches similar invention to the present application. Specifically, Krishna teaches systems, kits, and methods for administering a gel composition into a tumor of a subject and treating with laser light (e.g., for photoacoustic destruction of the tumor and tumor debris generation), where the gel comprises functionalized fullerenes (FFs) and a biocompatible polymer (abst). Schematic showing how photoacoustic or mechanical destruction of tumor leads to cellular debris that provides multitude of neoantigens from heterogeneous tumor for priming of immune system [0020].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with priming tumors as taught by Krishna because it helps to overcome current treatments shortcomings and lack approaches to localize to the tumor ([0004] of Krishna).
Regarding claim 14, Ferreira teaches all the claimed limitations except for repeating said pressure-pulse tumor priming.
However, in the same field of endeavor, Krishna teaches administering a gel into an initial tumor of a subject such that a treated tumor is generated such as well a tumor is of a larger size, the tumor is treated a second, third, or fourth time (e.g., for 1-5 minutes each time).
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with priming tumors repeating as taught by Krishna because it helps to overcome current treatments shortcomings and lack approaches to localize to the tumor ([0004] of Krishna).
Regarding claims 15 and 16, Ferreira teaches all the claimed limitations except for wherein said anticancer therapeutic agent is selected from the group consisting of an inhibitor to an inhibitory checkpoint molecule, an activator of a stimulatory checkpoint molecule, an antibody, a cytokine, an interferon, an interleukin, a vaccine, an oncolytic virus, chimeric antigen receptor T cells, and any combination thereof.
However, in the same field of endeavor, Krishna teaches administering Preclinical minimally invasive treatment strategies, such as photothermal treatment, utilize photothermal nanoparticles (metal, inorganic or polymer based) delivered to the tumor and exposed to deep-tissue penetrating near-infrared laser for heat generation and localized tumor destruction. The photothermal nanoparticles are delivered to the tumor by a) direct intratumoral injection, b) active targeting with [biological agent of] antibody conjugated nanoparticles, or c) passive targeting with enhanced permeation and retention (EPR) effect [0041].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with antibody as taught by Krishna because it helps to overcome current treatments shortcomings and lack approaches to localize to the tumor ([0004] of Krishna).
Regarding claim 20, Ferreira teaches all the claimed limitations except for wherein said therapeutic agent is a macromolecule.
However, in the same field of endeavor, Krishna teaches administering Preclinical minimally invasive treatment strategies, such as photothermal treatment, utilize photothermal nanoparticles (metal, inorganic or polymer based) delivered to the tumor and exposed to deep-tissue penetrating near-infrared laser for heat generation and localized tumor destruction. The photothermal nanoparticles are delivered to the tumor by a) direct intratumoral injection, b) active targeting with [biological agent of] antibody conjugated nanoparticles, or c) passive targeting with enhanced permeation and retention (EPR) effect [0041]. “fullerene” refers a general class of molecules that exists essentially in the shape of a three dimensional polyhedron containing from 20 to 1500 carbon atoms, and which comprises carbon atoms as the predominant element from which they are composed. These are molecular fullerenes which have had one or more of the atoms which comprise the fullerene cage structure replaced by an atom other than carbon, such as nitrogen, boron or titanium, yet essentially retain the geometry of a polyhedron upon being so substituted [0035].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with macromolecule as taught by Krishna because it helps to overcome current treatments shortcomings and lack approaches to localize to the tumor ([0004] of Krishna).
Regarding claim 21, Ferreira teaches all the claimed limitations except for wherein said therapeutic agent is a nanomedicine.
However, in the same field of endeavor, Krishna teaches administering Preclinical minimally invasive treatment strategies, such as photothermal treatment, utilize photothermal nanoparticles (metal, inorganic or polymer based) delivered to the tumor and exposed to deep-tissue penetrating near-infrared laser for heat generation and localized tumor destruction. The photothermal nanoparticles are delivered to the tumor by a) direct intratumoral injection, b) active targeting with [biological agent of] antibody conjugated nanoparticles, or c) passive targeting with enhanced permeation and retention (EPR) effect [0041]. “fullerene” refers a general class of molecules that exists essentially in the shape of a three dimensional polyhedron containing from 20 to 1500 carbon atoms, and which comprises carbon atoms as the predominant element from which they are composed. These are molecular fullerenes which have had one or more of the atoms which comprise the fullerene cage structure replaced by an atom other than carbon, such as nitrogen, boron or titanium, yet essentially retain the geometry of a polyhedron upon being so substituted [0035]. Method for cancer immunotherapy using photoacoustic gels and nanoparticles for minimally-invasive, mechanical destruction of tumors to produce multitude of antigens that stimulate immune system irrespective of heterogeneity in tumor immunogenicity [0038].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with nanomedicine as taught by Krishna because it helps to overcome current treatments shortcomings and lack approaches to localize to the tumor ([0004] of Krishna).
Claims 7-8 and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Ferreira et al (US 20140046246) in view of Krishna as applied to claim 1 and further in view of Guha et al (US 20200398084 A1).
Regarding claim 7, Ferreira teaches all the claimed limitations except for an endoscope.
However, in the same field of endeavor, Guha teaches systems, devices and methods for treating cancer and metastasis using low energy immune priming. The low energy immune priming includes administering immune-priming energy. The low energy immune priming can be combined with an adjunct therapy (abst). The methods, the one or more transducers comprise three-dimensional phased arrays. In an embodiment of the methods, the one or more transducers are incorporated into one or more endoscopic devices [0070].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with endoscope as taught by Guha because it would be helpful if other types of sub-ablative energy could be used to treat cancer ([0005] of Guha).
Regarding claim 8, Ferreira teaches all the claimed limitations except for endoscope is configured for insertion in a hollow organ.
However, in the same field of endeavor, Guha teaches systems, devices and methods for treating cancer and metastasis using low energy immune priming. The low energy immune priming includes administering immune-priming energy. The low energy immune priming can be combined with an adjunct therapy (abst). The methods, the one or more transducers comprise three-dimensional phased arrays. In an embodiment of the methods, the one or more transducers are incorporated into one or more endoscopic devices [0070]. fiber-optic to monitor the surface temperature and to insure patient comfort. The control circuit can comprise temperature probes for insertion into the patient in areas [0278].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with endoscope insertion in a hollow organ as taught by Guha because it would be helpful if other types of sub-ablative energy could be used to treat cancer ([0005] of Guha).
Regarding claim 17, Ferreira teaches all the claimed limitations except for herapeutic agent is a monoclonal antibody (mAb) used to treat cancer, or any combination of mAbs used to treat cancer.
However, in the same field of endeavor, Guha teaches systems, devices and methods for treating cancer and metastasis using low energy immune priming. The low energy immune priming includes administering immune-priming energy. The low energy immune priming can be combined with an adjunct therapy (abst). Anti-tumor immunotherapies encompassed herein (i) include monoclonal antibodies (including naked, chemo-, radio- or toxin-conjugated antibodies and also bispecific antibodies), relevant antigen-binding fragments thereof such as fragments comprised of Fab or scFv fragments, that that bind with high affinity to cancer-associated biomolecular targets; (ii) those that are non-specific with respect to tumor cells and tumor cell antigens; anti-tumor immunotherapies e.g. cytokines, interleukins, interferons, Flt3L, CD40L, GM-CSF, ligands and agonists, RIG1 helicase activators, anti-CD40, NKG2D ligand, anti-CSF1R, anti-TLR, TLR ligands, INF-α, TNF-β, anti-Tie2, small organic molecules (e.g. 1,500 daltons or less) or other drugs that bind to cytokines or cytokine receptors; and materials that target checkpoints including but not limited to one of CTLA-4, PD-1, PDL-1, and other small organic molecules, peptides and aptamers that target immune responses. In an embodiment, immunotherapy as used herein excludes bacteria-based anticancer or anti-tumor immunotherapies [0119].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with monoclonal antibody as taught by Guha because it would be helpful if other types of sub-ablative energy could be used to treat cancer ([0005] of Guha).
Regarding claim 18, Ferreira teaches all the claimed limitations except for wherein said therapeutic agent is selected from ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, cemiplimab, dostarlimab, tislelizumab, relatlimab, toripalimab, camrelizumab, sintilimab, or any combination thereof.
However, in the same field of endeavor, Guha teaches systems, devices and methods for treating cancer and metastasis using low energy immune priming. The low energy immune priming includes administering immune-priming energy. The low energy immune priming can be combined with an adjunct therapy (abst). Anti-tumor immunotherapies encompassed herein (i) include monoclonal antibodies (including naked, chemo-, radio- or toxin-conjugated antibodies and also bispecific antibodies), relevant antigen-binding fragments thereof such as fragments comprised of Fab or scFv tumor cell antigens; anti-tumor immunotherapies e.g. cytokines, interleukins, interferons, Flt3L, CD40L, GM-CSF, ligands and agonists, RIG1 helicase activators, anti-CD40, NKG2D ligand, anti-CSF1R, anti-TLR, TLR ligands, INF-α, TNF-β, anti-Tie2, small drugs that bind to cytokines or cytokine receptors; and materials that target checkpoints including but not limited to one of CTLA-4, PD-1, PDL-1, and other small organic molecules, peptides and aptamers that target immune responses [0119]. Targeted therapy Monocyte anti-CD40, NKG2D ligand, anti-CSF1R, and macrophage Myeloid anti-Tie2, anti-TLR, TLR ligands, INF-α, Derived Suppressor cell TNF-β, Targeted therapies Effector T cell targeting anti-OX40, 4-1BBL, anti-foxp40, TGF-β inhibitor, anti-CD137, artificial immunological synapse for T-cell activation, anti-CD47, anti-CD27, anti- GD2 Immune checkpoint inhibition anti-CTL4, anti-PD1, anti-VISTA, tim3, IDO inhibitor (e.g., Norharmane, Rosamarinic acid, COX-2 inhibitors, 1- Methyltryptophan, Epacadostat, navoximod) HSP targeted agents HSP105, HSP90, HSP70, HSP60, HSP27 [0111].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with therapeutic agent as taught by Guha because it would be helpful if other types of sub-ablative energy could be used to treat cancer ([0005] of Guha).
Regarding claim 19, Ferreira teaches all the claimed limitations except for wherein said therapeutic agent is a cytostatic or a cytotoxic drug bound to a plasma protein.
However, in the same field of endeavor, Guha teaches systems, devices and methods for treating cancer and metastasis using low energy immune priming. The low energy immune priming includes administering immune-priming energy. The low energy immune priming can be combined with an adjunct therapy (abst). Anti-tumor immunotherapies encompassed herein (i) include monoclonal antibodies (including naked, chemo-, radio- or toxin-conjugated antibodies and also bispecific antibodies), relevant antigen-binding fragments thereof such as fragments comprised of Fab or scFv tumor cell antigens; anti-tumor immunotherapies e.g. cytokines, interleukins, interferons, Flt3L, CD40L, GM-CSF, ligands and agonists, RIG1 helicase activators, anti-CD40, NKG2D ligand, anti-CSF1R, anti-TLR, TLR ligands, INF-α, TNF-β, anti-Tie2, small drugs that bind to cytokines or cytokine receptors; and materials that target checkpoints including but not limited to one of CTLA-4, PD-1, PDL-1, and other small organic molecules, peptides and aptamers that target immune responses [0119]. Targeted therapy Monocyte anti-CD40, NKG2D ligand, anti-CSF1R, and macrophage Myeloid anti-Tie2, anti-TLR, TLR ligands, INF-α, Derived Suppressor cell TNF-β, Targeted therapies Effector T cell targeting anti-OX40, 4-1BBL, anti-foxp40, TGF-β inhibitor, anti-CD137, artificial immunological synapse for T-cell activation, anti-CD47, anti-CD27, anti- GD2 Immune checkpoint inhibition anti-CTL4, anti-PD1, anti-VISTA, tim3, IDO inhibitor (e.g., Norharmane, Rosamarinic acid, COX-2 inhibitors, 1- Methyltryptophan, Epacadostat, navoximod) HSP targeted agents HSP105, HSP90, HSP70, HSP60, HSP27 [0111].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with therapeutic agent is a cytostatic or a cytotoxic drug as taught by Guha because it would be helpful if other types of sub-ablative energy could be used to treat cancer ([0005] of Guha).
Response to Arguments
Applicant's arguments have been fully considered but they are not persuasive at least for the following reasons;
Regarding the rejection of claim, the applicant argues the following;
3.2 FERREIRA ET AL. discloses a device to permeabilize the skin that is not intended to be inserted in the body, as it is evident from Figure 5. Ferreira et al is directed to laser-induced photoacoustic devices for transient permeabilization of biological barriers, particularly skin, for drug delivery. In contrast, claim 1 is directed to a pressure-pulse tumor-priming device configured to mechanically condition solid tumors using defined peak compressional pressures, defined pulse durations, controlled repetition rates, tumor-positioning support structure, spatially constrained tumor coupling, and time-limited exposure governed by a control system.
Initially, as per MPEP 2111, claims must be given their broadest reasonable interpretation consistent with the specification though understanding the claim language may be aided by explanations contained in the written description. Yet, it is important not to import into a claim limitation that are not part of the claim. As also the applicant states above, the claims merely recite, inter alia, “a pressure-pulse tumor-priming device configured to mechanically condition solid tumors using defined peak compressional pressures, defined pulse durations, controlled repetition rates, tumor-positioning support structure, spatially constrained tumor coupling, and time-limited exposure governed by a control system”
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., inserted in the body) 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 applicant further argues the following;
The cited reference neither discloses nor suggests these limitations, either individually or in combination, nor does it recognize tumor priming as a technical problem. Accordingly, claim 1 is novel under 35 U.S.C. §102 and non-obvious under 35 U.S.C. §103.
3.4. Examples 5 through 8 of Ferreira et al refer to "Transdermal Delivery" of a "dermatological formulation" and describe the delivery of a porphyrin or a protein to healthy skin. These examples never mention "tumor priming". There are no examples of tumor treatment in Ferreira et al, and no mention of tumor priming. The concept of "tumor priming" defined in our patent application as "[001] The present disclosure relates generally to the field of remodeling (or priming) of a tumor microenvironment (TME) to enhance the efficacy of anticancer therapeutic agents" is known since 2007 [D. L.G. Wientjes, Z. Tumor priming enhances delivery and efficacy of nanomedicines. 11). It was never an intent of Ferreira et al to disclose a device for tumor priming, there is no motivation to solve the problem of remodeling the tumor microenvironment because this problem is not formulated, and the device disclosed by Ferreira et al lacks essential features required to enable tumor priming of solid tumors inside the human body.
Initially as housekeeping items, the originally filed application did not include any IDS let alone this supporting document used as evidence “"[001] The present disclosure relates generally to the field of remodeling (or priming) of a tumor microenvironment (TME) to enhance the efficacy of anticancer therapeutic agents" is known since 2007 [D. L.G. Wientjes, Z. Tumor priming enhances delivery and efficacy of nanomedicines”
As clearly stated in the MPEP 608 which states “To obtain a valid patent, a patent application as filed must contain a full and clear disclosure of the invention in the manner prescribed by 35 U.S.C. 112(a). The requirement for an adequate disclosure ensures that the public receives something in return for the exclusionary rights that are granted to the inventor by a patent.”
Further, as per MPEP 609 the applicant must disclose a list of all patents, publications, applications, or other information submitted for consideration by the Office. U.S. patents and U.S. patent application publications must be listed in a section separately from citations of other documents. MPEP is very clear and states that “applicants and other individuals substantively involved with the preparation and/or prosecution of the application have a duty to submit to the Office information which is material to patentability as defined in 37 CFR 1.56. The provisions of 37 CFR 1.97 and 37 CFR 1.98 provide a mechanism by which patent applicants may comply with the duty of disclosure provided in 37 CFR 1.56 using an IDS. ”. MPEP also states “ A registered practitioner who receives information from a client without being informed whether the information was known for more than three months, however, cannot make the statement under 37 CFR 1.97(e)(2) without making reasonable inquiry. For example, if an inventor gave a publication to the attorney prosecuting an application with the intent that it be cited to the Office, the attorney should inquire as to when that inventor became aware of the publication and should not submit a statement under 37 CFR 1.97(e)(2) to the Office until a satisfactory response is received. ”
It is very clear that in light of the applicants’ own publications (see e.g., ARNAUT LUIS G ET AL. "Photoacoustic delivery and imaging methods in PDT", PROGRESS IN BIOMEDICAL OPTICS AND IMAGING, SPIE - INTERNATIONAL SOCIETY FOR OPTICAL ENGINEERING, BELLINGHAM, WA, US, vol. 11940, 04 March 2022, p. 119400A, XP060154529, ISSN: 1605-7422, DOI: 10.117/12.2609789 ISBN: 978-1-5106-0027-0) that was not provided to the office at the time of original filings.
In addition, the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Now turning to the other points in this section, regarding the argument of “cited reference neither discloses nor suggests these limitations, either individually or in combination, nor does it recognize tumor priming as a technical problem.” It is noted that tumor priming is merely recited in the PREAMBLE and as clearly stated in the MPEP 2111.02 Effect of Preamble “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent);”. Therefore, no weight is given to the limitations of tumor priming that is recited in the preamble of the claims.
The applicant further argues the following;
3.5.1 Different therapeutic purpose and target
While claim 1 is explicitly directed to tumor priming of solid tumors, requires coupling to a selected area of a solid tumor and includes controlled exposure duration (1 s - 60 min), Ferreira et al is directed to enhancing delivery of compounds through biological barriers, explicitly emphasizes skin, soft tissue, membranes and has no disclosure of tumor priming, oncology, or solid tumor treatment, which is a central aspect of the present patent application. Tumor priming is not disclosed or suggested in Ferreira et al.
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., tumor priming of solid tumors) 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).
Rather, claim merely recites “transducers with a selected area from a solid tumor”, “exposure of said solid tumor to said pressure pulses” no where in the claim, the argued “tumor priming of solid tumors” is recited.
The applicant further argues the following;
3.5.2 Pressure pulse definition is fundamentally different
Claim 1 of the present application requires pressure pulses with peak compressional pressures: 0.1-100 MPa and 90% pulse duration: 0.1-500 ns, while Ferreira et al describes "high-impulse broadband acoustic transients", but does not disclosure peak compressional pressure values in MPa nor temporal metrics defined as "90% pulse duration". Ferreira et al does teach the claimed magnitude-duration combination and could not teach them because the acoustic transients were
Contrary to the applicant’s assertion, the cited prior art specifically teaches optical power densities of 10 MW/cm2 per pulse, or less [0008]. ““Laser fluence” is the laser energy per unit area on the work material, expressed in units of J/cm2.
“Laser pulse duration” τL is the full width at 1/e level of the laser pulse [14], and is conveniently expressed in units of nanosecond, ns.
“Optical power density” is the power density of a laser beam, where the power density is the power of the laser by unit irradiation area, expressed in W/cm2 or more conveniently in MW/cm2… Impulse of an acoustic transient” is defined as the rate of pressure increase per unit of time, expressed in units of bar/s or more conveniently in bar/ns.
“Rise time of an acoustic transient” is defined as the time from 10% to 90% of the peak pressure [5].
“Broadband” is a wide frequency band that covers a continuous frequency spectrum and when used to qualify a pressure wave designates an acoustic emission with significant frequency components of tens of MHz [0009].
Further, Krishna also teaches provides multitude of neoantigens from heterogeneous tumor for priming [0020]. injected directly into the tumor (6-8 mm) followed by irradiation with NIR laser (300 J/cm2 [3MPa]). Photoacoustic treatment (PAG+Laser) leads to complete tumor regression [0022]. tumor of a subject and treating with laser light (e.g., for photoacoustic destruction of the tumor [0036].
As can be clearly and factually seen above, the cited prior art teaches the argued points.
Therefore, the rejections are maintained.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/SERKAN AKAR/ Primary Examiner, Art Unit 3797