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 .
Applicant’s reply and amendment filed 6/16/2026, are acknowledged. Claims 1-12, 17 and 19-24 are pending.
Response to Amendment
The rejection of claims 17 and 18-21 under 35 U.S.C. §101 are moot in view of the amendment to claim 17.
The rejection of claims 11 and 12 under 35 U.S.C. §102(a)(1) are moot in view of the amendment to claim 1.
Response to Arguments
In view of the amendment to claim 1, Applicant’s arguments with respect to the rejection of claims 1-3, 5, 6, 9, 10, 17 and 21-23 under 35 U.S.C. §102(a)(2) as being anticipated by Sartore et al. have been fully considered and are persuasive. The rejection has been withdrawn.
In view of the amendment to claim 1, Applicant’s arguments with respect to the rejection of claims 11 and 12 under 35 U.S.C. §102(a)(1) as being anticipated by Singh et al. have been fully considered and are persuasive. The rejection has been withdrawn.
In view of the amendment to claim 1, Applicant’s arguments with respect to the rejection of claims 1, 4, 7, 8, 17-20 and 24 under 35 U.S.C. §103 as being obvious over Li et al. and Kwan et al. have been fully considered and are persuasive.
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 9, 17 and 19-21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “substantially” in claim 9 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim. Although the specification suggest that a shell substantially consisting of one or more polypeptides means the shell “comprises at least 90% by weight , at least 95% by weight, preferably at least 98%, e.g. at least 99%, at least 99.5 or at least 99.9% by weight polypeptide,” 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).
Regarding claim 17, in traversing the rejection under 35 U.S.C. 101 for lack of a specific and substantial asserted utility the claim was amended as directed to a method for the site-specific delivery of polypeptide particles to a target site in a subject. The phrase “an effective amount” has been held to be indefinite when the claim fails to state the function which is to be achieved and more than one effect can be implied from the specification or the relevant art. In re Fredericksen, 213 F.2d 547, 102 USPQ 35 (CCPA 1954). Here, it is unclear what “an effective amount of polypeptide particles” or “composition” is intended to achieve. Nothing in the specification describes “an effective amount” pertaining to the function of site-specific delivery, nor “histotripsy or thermal ablation.” At best, the specification describes an effective amount pertaining to therapeutic or prophylactic treatment generally. See Specification (“Spec.”) at page 12, line 10. Apart from these general functions, specific uses are described such as “the treatment of tumors and removal of cardiac tissue in the treatment of heart disease.” Spec. at page 30, lines 20-21. Because more than one effect can be implied from the specification, the claim is indefinite.
Claims 19-21 which depend on claim 17 do not cure the deficiencies of claim 17 and are indefinite.
Claim Rejections - 35 USC § 102/103
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.
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.
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) 1, 4, 6, 7, 11, 17, 21 and 23 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Fernández et al. (US 2016/0038433).
Regarding claims 1 and 11, Fernández et al. teaches nanocapsules having a mean diameter of less than 1 µm and a protamine shell (current claim 4). See Abstract. Fernández et al. is silent as to whether the particle has one or more surface indentations. However, the method of making the nanocapsules comprise steps, which encompasses the steps of claim 11, such as preparing an organic solution including volatile oils, see paras. [0084] and [0092], mixing with an aqueous solution comprising protamine, see para. [0091], evaporating organic solvents and obtaining an oil core and a protamine shell (current claim 7). See para. [0089]. Because the process of Fernández et al. is similar to the method of making a polypeptide particle as claimed, the resulting nanocapsule of Fernández et al. would be expected to have one or more surface indentations and be capable of inducing cavitation on exposure to ultrasound. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Regarding claim 6, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Regarding claim 17, Fernández et al. teaches that “[t]he polypeptide provides, among other properties, stability to the nanocapsule as well as protection, penetration capacity and specificity in its interaction with given target cells.” Para. [0066]. This reads on “site-specific delivery of polypeptides particles to a target site in a subject.”
Regarding claim 21, Fernández et al. teaches incorporation of docetaxel, which is not a pathogenic antigen protein (current claim 23). See para. [0278].
Claim(s) 1-4, 7-12 and 22-24, is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Mo et al. (WO 2019/040282 A1).
Regarding claims 1 and 11, Mo et al. teaches nanoparticles and microspheres for delivering an anticancer agent to a subject. Mo et al. teaches the nanoparticles and microspheres are formed from a core that is encased by a coating or shell comprising an albumin-somatostatin fusion protein (current claims 9 and 21). See Abstract. Mo et al. teach two non-linear acoustic processes are involved in the formation of stable polymeric shells (i.e., acoustic emulsification and cavitation) via crosslinking of disulfide bonds (current claim 2). See page 49, para 2. “The size range of particles obtained by this technique can be 0.1 micron to 20 microns” (current claim 4). Id. Mo et al. further teach a polymeric shell containing a solid core of pharmacologically active agent produced by initially dissolving the pharmacologically active agent in a volatile organic solvent (e.g. benzene), forming the polymeric shell and evaporating the volatile solvent under vacuum, e.g., in a rotary evaporator, or freeze-drying the entire suspension (current claim 12). See page 52, lines 12-16. Because the process of Mo et al. is similar to the method of making a polypeptide particle as claimed, the resulting nanoparticle of Mo et al. would be expected to have one or more surface indentations and be capable of inducing cavitation on exposure to ultrasound. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
With respect to claims 3 and 24, MO et al. teach albumin of somatostatin-albumin fusion proteins including human serum albumin and/or derivatives of somatostatin. See lines 13-15.
With respect to claim 7, Mo et al. teach the core containing therapeutic agent within the protein shell can be a solid or liquid. Mo et al. teach the use of nonaqueous liquid (reading on water-immiscible liquid) that is capable of suspending or dissolving the pharmacologically active agent, but does not chemically react with either the polymer employed to produce the shell, or with the pharmacologically active agent itself. Mo et al. teach the water-immiscible liquid can be vegetable oil or a nonaqueous liquid (current claim 8). Page 44, lines 21-31.
With respect to claim 10, Mo et al. teach the albumin fusion protein nanoparticle composition further comprising a carrier. Page 9, lines 16-17; page 54, para 2; Claim 43).
With respect to claim 22, Mo et al. teach the polypeptide shell is a chimeric protein comprising human serum albumin fusion to somatostatin (p18, line 26-30). Neither human serum albumin nor somatostatin is an immunomodulatory polypeptide, reading on the polypeptide shell comprising at least 95% by weight non-immunomodulatory polypeptides.
With respect to claim 23, Mo et al. teach particles are capable of being sterile-filtered before use in the form of a liquid suspension. The ability to sterile-filter the end product of the invention formulation process (i.e., the drug particles) is of great importance since it is impossible to sterilize dispersions which contain high concentrations of protein (e.g., serum albumin) by conventional means such as autoclaving. The sterile-filter will remove bacteria reading on “no contain a pathogenic antigen protein.”
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.
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) 1, 4, 6, 7, 11, 17, 21 and 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wagstaffe et al. (WO 2012/066334) in view of Fernández et al. (US 2016/0038433).
Regarding claim 1, Wagstaffe et al. teaches “nanoparticles having a diameter in the range of 10 to 1000 nm and surface features having a depth in the range from 5 to 50 nm.” Abstract. The nanoparticles may be used for “initiating acoustic cavitation when exposed to pressure waves such as ultrasound.” Page 1, lines 1-2. To this end, Wagstaffe et al. teaches that the nanoparticles may be produced by either a single or double emulsion method which encompass the steps of claim 11. For example, adding a volatile material such as camphor to an organic solvent which is not miscible in water. See Spec. at page 12, lines 25-29. Further, emulsification may be performed using high pressure homogenization which implies subjecting the particle to reduced pressure conditions when the mixture exits the narrow value. See Spec. at page 12, lines 30-31.
Wagstaffe et al. does not teach “a polypeptide shell,” but does teaches that an aim of the invention is to use produce biocompatible nanoparticles. See page 2, lines 4-5. For instance, “[p]articles can consist of a range of materials including, but not limited to (i) natural and synthetic biocompatible and/or biodegradable polymers such as poly(lactic acid), poly(lactic-coglycolic acid), poly( caprolactone ), poly( ethylene glycol), (ii) inorganic material such as gold, silicon and titanium dioxide, etc.” Page 2, lines 26-30.
Fernández et al. teaches nanocapsules having a mean diameter of less than 1 µm and a protamine shell (current claim 4). See Abstract. “The polypeptide provides, among other properties, stability to the nanocapsule as well as protection, penetration capacity and specificity in its interaction with given target cells.” Para. [0066]. Like Wagstaffe, the method of making the nanocapsules comprise steps, which encompasses the steps of claim 11, such as preparing an organic solution including volatile oils, see paras. [0084] and [0092], mixing with an aqueous solution comprising protamine, see para. [0091], evaporating organic solvents and obtaining an oil core and a protamine shell (current claim 7). See para. [0089].
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the invention to combine the teachings of Wagstaffe et al. and Fernández et al. and arrive at the claimed invention. A rationale in support of the obviousness conclusion is that a method of enhancing a particular class of devices had been made part of the ordinary capabilities of one skill in the art based upon the teaching of such improvement in other situations, and that a skilled artisan would have been capable of applying this known method of enhancement to a “base” device in the prior art and the results would have been predictable to one of ordinary skill in the art. Here, Wagstaffe et al. teaches the base component of particle for inducing cavitation upon which the claimed invention can be seen as an “improvement.” Meanwhile, Fernández et al. teaches a comparable device that has been improved in the same way as the claimed invention, namely the inclusion of shell material comprising a biocompatible polypeptide such as protamine. A skilled artisan could have applied the known “improvement” motivated by the desire to improve upon or diversify the application of Wagstaffe et al.'s nanoparticles would have recognized that applying a polypeptide such as protamine would have yield predictable results.
Regarding claim 6, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Regarding claim 17, Fernández et al. teaches that “[t]he polypeptide provides, among other properties, stability to the nanocapsule as well as protection, penetration capacity and specificity in its interaction with given target cells.” Para. [0066]. This reads on “site-specific delivery of polypeptides particles to a target site in a subject.”
Regarding claim 21, Fernández et al. teaches incorporation of docetaxel, which is not a pathogenic antigen protein (current claim 23). See para. [0278].
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.
Claim 1-12, 17 and 19-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 17-25 of copending Application No. 18/272,113 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to a polypeptide particle for inducing cavitation on exposure to ultrasound comprising a core, a polypeptide shell having one or more surface indentions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S CABRAL whose telephone number is (571)270-3769. The examiner can normally be reached M-F 8 am - 5 pm.
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, Ali Soroush can be reached at 571-272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT S CABRAL/ Primary Examiner, Art Unit 1614
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