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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/18/2026 has been entered.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 84, 88-91, and 93-103 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-10, 13-20 of U.S. Patent No. 12,011,619 in view of Saha et al. (“Low intensity focused ultrasound (LOFU) modulates unfolded protein response and sensitizes prostate cancer”, 2014). Patent ‘619 encompasses the instant claimed subject matter of a method for priming a subject having a cancer (encompassed by preamble of claim 1), the method comprising: applying a priming therapy comprising a non-ablative ultrasound comprising at least two ultrasound beams to a treatment zone in the subject having the cancer, wherein the at least two ultrasound beams have different frequencies (encompassed by applying a priming therapy in claim 1), wherein the at least two ultrasound beams have a beam profile waist at -3 dB is not less than 5 mm in the treatment zone (encompassed by ultrasound beam in claim 1); wherein the ultrasound delivers an energy in the range of 300 to 3000 J/cm3 in the treatment zone of the subject (encompassed by energy in claim 92); and administering a chemotherapeutic agent to the subject (encompassed by chemotherapeutic agent, HSP90 inhibitor, in claim 1). Patent ‘619 does not claim wherein the chemotherapeutic agent effects an endoplasmic reticulum stress and/or an unfolded protein response in the cancerous cell. However, Saha et al. discloses in the same field of endeavor LOFU (non-cavitational; page 435, column 2, lines 2-3) and chemotherapeutic agents that generates ER stress and modulates UPR (abstract; page 435, column 1, line 12 to column 2, line 5; HSP90 inhibitor). Therefore, it would have been obvious to one of ordinary skill in the art as evidenced by Saha et al. for LOFU and chemotherapeutic agents, e.g. HSP90 inhibitor, to generate ER stress and modulate UPR. Claim 88 is encompassed by claim 3 of ‘619. Claim 89 is encompassed by claim 4 of ‘619. Claim 90 is encompassed by claim 5 of ‘619. Claim 91 is encompassed by claim 6 of ‘619. Claim 93 is encompassed by claim 7 of ‘619. Claim 94 is encompassed by claim 20 of ‘619. Claim 95 is encompassed by claim 15 of ‘619. Claim 96 is encompassed by claim 16 of ‘619. Claim 97 is encompassed by claims 8-9 of ‘619. Claim 98 is encompassed by claim 10 of ‘619. Claim 99 is encompassed by claim 8 of ‘619. Claim 100 is encompassed by claim 13 of ‘619. Claim 101 is encompassed by claim 14 of ‘619. Claim 102 is encompassed by claim 17 of ‘619. Claim 103 is encompassed by claim 18 of ‘619.
Claims 85-87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,011,619 in view of Saha et al. (“Low intensity focused ultrasound (LOFU) modulates unfolded protein response and sensitizes prostate cancer”, 2014) further in view of Andruska et al. (WO 2014/113820). Patent ‘619 discloses instant claimed subject matter (see above) of a method for priming a subject having a cancer (encompassed by preamble of claim 1), the method comprising: applying a priming therapy comprising a non-ablative ultrasound comprising at least two ultrasound beams to a treatment zone in the subject having the cancer, wherein the at least two ultrasound beams have different frequencies (encompassed by applying a priming therapy in claim 1), wherein the at least two ultrasound beams have a beam profile waist at -3 dB is not less than 5 mm in the treatment zone (encompassed by ultrasound beam in claim 1); and administering a chemotherapeutic agent to the subject (encompassed by chemotherapeutic agent, HSP90 inhibitor, in claim 1). Patent ‘619 does not claim an estrogen receptor alpha inhibitor comprising BHPI. However, Andruska et al. teaches in the same field of endeavor a chemotherapeutic agent such as an estrogen receptor alpha inhibitor comprising BHPI ([009]; [0039]). Therefore, it would have been obvious to one of ordinary skill in the art to have substituted the chemotherapeutic agent for an estrogen receptor alpha inhibitor as taught by Andruska et al. as one chemotherapeutic agent for another is well within the skill level of one of ordinary skill in the art.
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.
Claim(s) 84, 88, 90-91, and 93-103 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saha et al. (“Low intensity focused ultrasound (LOFU) modulates unfolded protein response and sensitizes prostate cancer”, 2014) in view of Chao et al. (US 2015/0157383) and Czarnota et al. (US 2015/0196638).
Saha et al. discloses a method for priming a subject having a tumor for a chemotherapeutic agent (abstract), the method comprising applying non-ablative, non-cavitational ultrasound (non-ablative, non-cavitational LOFU; page 435, column 2, lines 2-3); Saha discloses energy in the range of 300 to 3000 J/cm3 in the treatment zone of the subject (page 435, col. 2; same operating parameters: frequency, duration, and intensity); and administering the chemotherapeutic agent to the subject, wherein the chemotherapeutic agent comprises a heat shock protein 90 (HSP90) inhibitor (page 2, col. 1), wherein the HSP90 inhibitor comprises 17AAG (page 2, col. 1); wherein the chemotherapeutic agent effects an ER and/or UPR in the cancerous cell (abstract; page 435, column 1, line 12 to column 2, line 5; HSP90 inhibitor). Saha et al. does not teach at least two ultrasound beams to a treatment zone, wherein the at least two ultrasound beams have different frequencies. However, Chao et al. teaches in the same field of endeavor an ultrasonic medical device applying low intensity focused ultrasound ([0116]) using two ultrasonic beams having different frequencies ([0116]) to form composite ultrasound ([0116]). Therefore, it would have been obvious to one of ordinary skill in the art to have provided Saha et al. with the two ultrasound beams as taught by Chao et al. to form a composite ultrasound at the region of interest ([0096]).
Saha et al. discloses the subject matter substantially as claimed except for a beam profile waist at -3 dB is not less than 5 mm in the treatment zone. However, Czarnotal et al. teaches in the same field of endeavor an ultrasound beam width at -3 dB is not less than 5 mm ([0064]). Therefore, it would have been obvious to one of ordinary skill in the art to have provided Saha et al. with the beam width as taught by Czarnotal et al. as the use of such ultrasound beam parameters to target tumor cells is well known.
With respect to claim 88, Saha et al. discloses a frequency range of 0.01 to 10 MHz (page 435, col. 2) and a spatial peak temporal average acoustic intensity between 1 and 1000 W/cm2 in the treatment zone (page 435, col. 2).
With respect to claim 90, Saha et al. discloses a frequency in the range of 300 kHz to 3 MHz (page 435, col. 2).
With respect to claim 91, Saha et al. discloses wherein the spatial peak temporal average acoustic output intensity is between 10 and 300 W/cm2 in the treatment zone (page 435, col. 2).
With respect to claim 93, Saha et al. discloses wherein the ultrasound beam is applied for 0.5 to 5 seconds (page 435, col. 2).
With respect to claim 94, Saha et al. discloses wherein the treatment zone is configured to reach a maximum temperature of less than 55 degrees C, which is evidenced by Chao et al. (LOFU prodcues less heat than HIFU; Less than 54 degrees C to prevent heat injury; [0108]; [0116]; [0124]).
With respect to claims 95-96; Chao et al. discloses emitting the two ultrasound beams sequentially or simultaneously ([0127]).
With respect to claims 97-99, Saha et al. discloses increasing ER stress (page 435, col. 1).
With respect to claims 100-101, Saha et al. discloses combining LOFU with chemotherapeutic agent but does not specifically recite before or concurrent. However, it would have been obvious to one of ordinary skill in the art to have try LOFU before or concurrent with the chemotherapeutic agent as there is a finite number of identified, predictable solutions, with a reasonable expectation of success (before, concurrent, or after).
With respect to claim 102, Saha et al. discloses prostate tumor (page 435, col. 1).
With respect to claim 103, Saha et al. discloses resistance to chemotherapeutic agents (page 435, col. 1).
Claim(s) 85-87 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saha et al. (“Low intensity focused ultrasound (LOFU) modulates unfolded protein response and sensitizes prostate cancer”, 2014) in view of Chao et al. (US 2015/0157383) and Czarnota et al. (US 2015/0196638) as applied to claim 84, further in view of Andruska et al. (WO 2014/113820).
Saha et al. discloses the subject matter substantially as claimed except for an estrogen receptor alpha inhibitor comprising BHPI. However, Andruska et al. teaches in the same field of endeavor a chemotherapeutic agent such as an estrogen receptor alpha inhibitor comprising BHPI ([009]; [0039]). Therefore, it would have been obvious to one of ordinary skill in the art to have substituted the chemotherapeutic agent for an estrogen receptor alpha inhibitor as taught by Andruska et al. as one chemotherapeutic agent for another is well within the skill level of one of ordinary skill in the art.
Claim(s) 89 is/are rejected under 35 U.S.C. 103 as being unpatentable over Saha et al. (“Low intensity focused ultrasound (LOFU) modulates unfolded protein response and sensitizes prostate cancer”, 2014) in view of Chao et al. (US 2015/0157383) and Czarnota et al. (US 2015/0196638) as applied to claim 88, further in view of KOST et al. (US 2014/0257146).
Saha et al. discloses the subject matter substantially as claimed except for a frequency range of 30 to 300 KHz. However, KOST et al. teaches in the same field of endeavor using low frequency ([074]); 20 KHz – 200 KHz; [0086]) in combination with chemotherapeutic agents ([0100]). Therefore, it would have been obvious to one of ordinary skill in the art to have provided Saha et al. with the frequency range as taught by KOST et al. as it is well known to use low frequency in combination with chemotherapeutic agents ([0100]).
Response to Arguments
Applicant's arguments filed 2/18/2026 have been fully considered but they are not persuasive.
Applicant argues the reference does not teach wherein the ultrasound delivers an energy in the range of 300 to 3000 J/cm3 in the treatment zone of the subject. However, Saha et al. discloses energy in the range of 300 to 3000 J/cm3 in the treatment zone of the subject (page 435, col. 2). The Examiner’s position is that Saha discloses the same operating parameters: frequency (1 MHz), duration (1.5s), and intensity (270 W/cm2). The Examiner notes that one of ordinary skill in the art is capable of calculating intensity into energy (energy = intensity x duration).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Saha discloses the subject matter substantially as claimed except for least two ultrasound beams to a treatment zone, wherein the at least two ultrasound beams have different frequencies. However, Chao et al. teaches in the same field of endeavor an ultrasonic medical device applying low intensity focused ultrasound ([0116]) using two ultrasonic beams having different frequencies ([0116]) to form composite ultrasound ([0116]). Therefore, it would have been obvious to one of ordinary skill in the art to have provided Saha et al. with the two ultrasound beams as taught by Chao et al. to form a composite ultrasound at the region of interest ([0096]). Chao et al. is only relied upon to teach a composite ultrasound beam, whereas Saha et al. discloses LOFU. Saha discloses the subject matter as claimed except for a beam profile waist at -3 dB is not less than 5 mm in the treatment zone. However, Czarnotal et al. teaches in the same field of endeavor an ultrasound beam width at -3 dB is not less than 5 mm ([0064]). Therefore, it would have been obvious to one of ordinary skill in the art to have provided Saha et al. with the beam width as taught by Czarnotal et al. as the use of such ultrasound beam parameters to target tumor cells is well known. The Examiner notes that the features relied upon (beam profile and beam width) are distinct from and does not affect whether the ultrasound is non-ablative, non-cavitational or ablative and cavitational and can be applied to ultrasound regardless if it is non-ablative, non-cavitational or ablative and cavitational.
Applicant’s arguments with respect to double patenting have been considered but are not persuasive. Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER LUONG whose telephone number is (571)270-1609. The examiner can normally be reached M-F 9-6.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anhtuan T Nguyen can be reached at (571)272-4963. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PETER LUONG/Primary Examiner, Art Unit 3797