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 .
Application Number Error
The Examiner notes that the Claim set, Remarks and Response to Election/Restriction Requirement all filed, 12/02/2025, are directed to application number: 18/468,329. The Application number is 18/333,946. The Examiner does not believe this error has affected the response herein as the arguments and claims are directed to the substance of Application number 18/333,946. The Examiner notes the error so the Applicant can correct the error in the next response.
Election/Restrictions
Applicant’s election without traverse of Invention A in the reply filed on 12/02/2025 is acknowledged.
Claim(s) 6-8, 10-11 & 18-20 is/are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/02/2025.
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.
Claim(s) 3-5 is/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 3-5
Claim 3 claims “wherein the bolus is selected”. However the selection is not positively claimed as a method step. This leads to confusion over whether the selection is being performed or is merely intended. Additionally the claim limitation implies a function being applied in determining the selection. Further the claim limitation of “velocity distribution that is greater as a function of a desired targeting volume” is not well understood. Based on the Specification of the Applicant a relationship between velocity distribution of the MTB and the desired target is disclosed. It is the understanding of the Examiner that the claim limitations are directed to claiming the that relationship. However, the claim language in Claims 3-5 are confusing in trying to claim when to select the broadest velocity distribution and when to select the narrowest. For example, “a greater targeting volume” should be “a larger targeting volume” for Claim 4. Another example, “concentrated targeting is sought for increasing the concentration of magneto-aerotactic-responsive bacteria targeting one or more hypoxic regions” for Claim 5. It appears the “concentrated targeting” means a smaller targeting volume.
In Claim 3, the terms, target zone and targeting volume, appear to be the same but it isn’t clear. It isn’t understood if the hypoxic regions are apart of the targeting zone, the targeting volume or neither. Claims 3-5 should be amended to better and more clearly claim the selection method.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-2, 9 12 & 14-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Martel et al. (Sylvain Martel et al. Flagellated Magnetotactic Bacteria as Controlled MRI-trackable Propulsion and Steering Systems for Medical Nanorobots Operating in the Human Microvasculature. Int J Rob Res. 2009 Apr 1;28(4):571-582; enclosed herein).
Claim 1: Martel teaches –
A method of at least one of obtaining imaging information, diagnosis and treatment of a subject [MRI could potentially be used to track MTB in 3D inside the human body, providing a superior imaging modality] (Page 577; Section 4: Tracking Magnetotactic Bacteria-based Nanorobots with Magnetic Resonance Imaging) using magneto-aerotactic-responsive bacteria adapted to self-locomote [Counter-clockwise rotations of a polar flagellum thrust the cell forward] (Page 573; Section 3: Propulsion and Terminal Velocity),
the method comprising:
obtaining imaging information [superior imaging modality] (Page 577; Section 4: Tracking Magnetotactic Bacteria-based Nanorobots with Magnetic Resonance Imaging) of a target zone in the subject (See Page 579; Section 9: Targeting Strategy),
whereby a bolus of magneto-aerotactic-responsive bacteria [Magnetotactic Bacteria (MTB)] (Page 572, Section 1: Introfuction) is injected into the subject [delivery of therapeutic agents to a tumoral lesion requiring transitions through capillary sections of the human microvasculature] (Page 574; Section 3.2) [Catheter Reaching Limit] (Figure 12),
Examiner’s Note: While the claim term, injected, is not used, it is understood based on Martel that the MTB is being injected through a catheter and into the human vasculature.
the magneto-aerotactic-responsive bacteria [Magnetotactic Bacteria (MTB)] (Page 572, Section 1: Introfuction) attached to at least one of the group consisting of: a therapeutic agent, a diagnostic agent and an imaging agent [carrying therapeutic agents] (Page 574; Section 3.2);
applying a magnetic field at a first magnetic field intensity [The data in Figure 5 were recorded with a group of 30 bacteria under a directional field of 20 Gauss at constant environmental conditions] (Page 576, Section 3.3: Capillary Wall Effect on Bacterial Nanorobots) to guide and cause a displacement of the magneto-aerotactic responsive bacteria towards the target zone [polar magneto-aerotaxis keeps cells at the preferred oxygen concentration at the oxic–anoxic interface] (Page 578, Section 5. Steering Control) having hypoxic regions [to enhance tumor targeting where a decrease in the oxygen concentration exists] (Page 578, Section 5. Steering Control) through magnetotaxis [chain of magnetosomes imparts to the MTB a magnetic moment that generates sufficient torque so that the bacteria can align themselves to magnetic field lines. This is referred to as magnetotaxis] (Page 577, Section 5: Steering Control); and
Examiner’s Note: While Martel teaches the claim limitation, to guide and cause a displacement…through magnetotaxis, the Examiner notes the claim limitation is intended use of applying a magnetic field.
applying a magnetic field with a second magnetic field intensity that is less than the first magnetic field intensity for allowing the magneto-aerotactic responsive bacteria to follow an oxygen gradient that draws the bacteria to the hypoxic regions [3 Gauss (or even less) provides the best control and response of the MTB from directional commands generated by an electrical source by making magnetotaxis the predominant factor over chemotaxis and aerotaxis] (Page 578, Section 5. Steering Control) [polar magneto-aerotaxis keeps cells at the preferred oxygen concentration at the oxic–anoxic interface. This feature could potentially be integrated at a specific moment in the control protocol to enhance tumor targeting where a decrease in the oxygen concentration exists] (Page 578, Section 5. Steering Control) [The swimming direction of MTB is influenced not only by magnetotaxis, but also by aerotaxis and chemotaxis. Aerotaxis is defined as the movement of an organism, especially a bacterium, toward or away from air or oxygen] (Para 578, Section 5. Steering Control)
Examiner’s Note: The first field was 20 Gauss and the second field was 3 Gauss and thus, the second field is less than the first. Further while the prior art teaches magnetotaxis is the predominant factor that does not mean that aerotaxis has no influence.
wherein there is an increase in changes of direction of movement of the magneto-aerotactic responsive bacteria from a direction of the magnetic field at the second magnetic field intensity than at the first magnetic field intensity (Page 578, Section 5. Steering Control and See Examiner’s Note),
Examiner’s Note: The claim limitation is directed to an increase in a specific type of motion. The Specification of the Applicant discloses two types of motion: run-and-tumble and run-and-reverse. The claim limitation is direct to more run-and-tumble motion at lower magnetic intensities. While the prior art of Martel does not specifically use the run-and-tumble and run-and-reverse terminology, the prior art of Martel recognizes the types of motion in magnetotaxis movement (run-and-reverse) and aerotaxis movement (run-and-tumble). The prior art of Martel explains that as the magnetic intensity decreases the influence of aerotaxis (run-and-tumble) increase and as the magnetic intensity increases the influence of magnetotaxis (run-and-reverse) increases. Thus, the Examiner contends that while using different terminology the prior art of Martel reads on the claim limitation. Another note is that the prior art of Martel and the Specification of the Applicant disclose similar/same MTBs of AMB-1 and MSR-1. This further supports the assertion of the Examiner that the MTBs of the prior art of Martel would behave in the same manner as claimed.
for at least one of the group consisting of: treatment, diagnosis and imaging of the subject [MTB were imaged using a fast spin echo sequence. These results suggest that MRI could potentially be used to track MTB in 3D inside the human body, providing a superior imaging modality compared to existing medical imaging methods for this particular application] (Page 577, Section 4. Tracking Magnetotactic Bacteria-based Nanorobots with Magnetic Resonance Imaging).
Claim 2/1: Martel teaches further comprising obtaining velocity distribution information of the magneto-aerotactic-responsive bacteria of the bolus (See Exhibit 1 below) to predict a spread post-injection of the magneto-aerotactic-responsive bacteria in the subject when the magnetic field intensity is at the first magnetic field intensity (intended use and holds little to no patentable weight).
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[AltContent: textbox (Exhibit 1 – Figure 2 of Martel)]Examiner’s Note: The claim limitation of “to predict” is not a method step of predicting. Rather the “to predict” claim limitation is the intended use of the step of obtaining velocity distribution information.
Claim 9/1: Martel teaches wherein the obtaining imaging information of a tumor of a subject [medical nanorobots may prove to be more effective for fighting tumors] (Page 579, Section 9. Targeting Strategy and Figure 12) is performed using an MRI or a CT scanner [conventional clinical MRI system] (Page 580, Section 10. Robotic Platform).
Claim 12/1: Martel teaches whereby the bolus of magneto-aerotactic-responsive bacteria is injected into a peripheral region of the tumor [medical nanorobots may prove to be more effective for fighting tumors] (Page 579, Section 9. Targeting Strategy and Figure 12).
Claim 14/1: Martel teaches further comprising, after the reducing the magnetic field intensity of the magnetic field to a second magnetic field intensity, further reducing the magnetic field intensity of the magnetic field to a third magnetic field intensity [0.5 Gauss] (Page 578, Section 5. Steering Control) that is less than the second magnetic field intensity, wherein the magneto-aerotactic-responsive bacteria further exhibit an increase in changes of direction of movement of the magneto-aerotactic responsive bacteria from the direction of the magnetic field at the third magnetic field intensity than at the second magnetic field intensity (Page 578, Section 5. Steering Control and See Examiner’s Note on Page 6, as the same logic applies to the second and third magnetic field)
Claim 15/14/1: Martel teaches wherein the second magnetic field intensity is of a value of 0 Gauss or above, but less than 5 Gauss [3 Gauss (or even less)] (Page 578, Section 5. Steering Control).
Claim 16/1: Martel teaches wherein the first magnetic field intensity is at least 15 Gauss [20 Gauss] (Page 576, Section 3.3: Capillary Wall Effect on Bacterial Nanorobots).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Martel et al. (Sylvain Martel et al. Flagellated Magnetotactic Bacteria as Controlled MRI-trackable Propulsion and Steering Systems for Medical Nanorobots Operating in the Human Microvasculature. Int J Rob Res. 2009 Apr 1;28(4):571-582; enclosed herein) and further in view of Martel (Sylvain Martel; Swimming microorganisms acting as nanorobots versus artificial nanorobotic agents: A perspective view from an historical retrospective on the future of medical nanorobotics in the largest known three-dimensional biomicrofluidic networks. Biomicrofluidics 1 March 2016; 10 (2): 021301; enclosed herein and referenced herein as Martel‘2016).
Claim 13/1: Martel fails to teach wherein a plurality of boluses is injected into said subject at different sites on said subject. However, Martel‘2016 teaches wherein a plurality of boluses [series of repeated scheduled injections] (Page 021302-12) is injected into said subject at different sites on said subject [peritumoral injections] (Page 021301-14) in order to yield significant therapeutic effects (Page 021302-12).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Martel with the multiple injects as taught by Martel‘2016 in order to yield significant therapeutic effects (Page 021302-12).
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Martel et al. (Sylvain Martel et al. Flagellated Magnetotactic Bacteria as Controlled MRI-trackable Propulsion and Steering Systems for Medical Nanorobots Operating in the Human Microvasculature. Int J Rob Res. 2009 Apr 1;28(4):571-582; enclosed herein).
Claim 17/1: Martel fails to specifically teach wherein the second magnetic field intensity is less than 15 Gauss, but more than or equal to 5 Gauss. However, Martel teaches applying Gauss between 0.5 to 300 Gauss or more (Figure 6) as the different magnetic intensities result in a relationship between aerotaxic and magnetotaxic movement of the MTB in how the operator wants to steer the MTB (Page 577-578, Section Steering Control and Page 576, Section 3.4 Controlling the Velocity of Bacterial Nanorobots).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Martel to use Gauss between 5-15 as Martel obviously teaches the different magnetic intensities result in a relationship between aerotaxic and magnetotaxic movement of the MTB in how the operator wants to steer the MTB (Page 577-578, Section Steering Control and Page 576, Section 3.4 Controlling the Velocity of Bacterial Nanorobots).
Allowable Subject Matter
Claim(s) 3-5 is considered to overcome the prior art if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action. Martel teaches in Section 2.1 Choice of MTB how MTB is known to be selected based on swimming direction. Martel and the prior art fail to recognize the relationship between targeting volume and/or hypoxic regions and velocity distribution of the MTBs in the selection process. However, Claims 3-5 are being interpreted as best understood by the Examiner. It is possible that in amending the 35 USC § 112 rejections that a new interpretation is applied and the claims are no longer overcome the prior art.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Gordon (U.S. Patent Application 2003/0120202 A1) – Gordon teaches a method and system for delivering a medical agent to targeted tissues in a patient, and subsequently removing systemically distributed medical agent to minimize exposure of non-targeted portions of a patient's body to the medical agent. The patient is treated with a targeted medical agent that includes a therapeutic component, a targeting component, and a magnetically attracted component. The targeting component, such as an antibody known to be attracted to an antigen present at the target, causes a concentration of the targeted medical agent to occur at the targeted tissue. The medical agent not concentrated at the targeted tissue is removed by withdrawing and magnetically filtering a portion of the patient's blood to remove the targeted medical agent, and returning the filtered blood to the patient.
Martel (U.S. Patent Application 2006/0073540 A1) – Martel teaches moving components with dimensions much smaller than what micro-electro-mechanical system (MEMS) technology can accomplish in terms of force generated and power efficiency, are integrated onto micro-systems. These moving components referred to herein as "bio-components" are special bacteria (magnetotactic bacteria) where the motion of these bio-components can be controlled by generating an "artificial pole" by a magnetic field generated by a constant electrical current that can be varied to change the location of the "artificial pole" from an electrical system such as an embedded electronic micro-circuit. According to the present invention, it is possible through a software program or codes, to control the direction of motion of these magnetotactic bacteria, for example, by downloading such program onto the embedded electronics (controller or the like), and to generate the required magnetic field to control such bacteria to accomplish a particular task. Moreover, though integrated sensory means and new algorithms, the magnetotactic bacteria-based system could adapt or change the direction of motion from new occurring conditions.
Haik (U.S. Patent Application 2009/0068112 A1) – Haik teaches a medical imaging system that enables the discovery of malignant tissue utilizing contrast agents and heating agents made of magnetic nanoparticles that are delivered to tumor sites utilizing attenuated strains of bacteria that seek and reside at tumor sites is disclosed. The thermal contrast agents may be temperature self-controlled magnetic nanoparticles that may be encapsulated in a biocompatible coating. The thermal contrast agents may be uploaded into attenuated strains of bacteria that seek and reside in tumor tissue when placed into a bloodstream of a patient. An alternating magnetic field device with a prescribed frequency range may be used to induce heating of the magnetic nanoparticles in the patient, and a thermal scan may be utilized to identify tumors. In another embodiment, the contrast agent may be formed from magnetic nanoparticles having distinct magnetic moment profiles, and a MRI system may be utilized to identify tumors with such contrast agent.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HELENE C BOR whose telephone number is (571)272-2947. The examiner can normally be reached Mon - Fri 10:30 - 6:30.
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/Helene Bor/Examiner, Art Unit 3797
/CHRISTOPHER KOHARSKI/Supervisory Patent Examiner, Art Unit 3797