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 .
Claims 1-7, 9, 10, 12-14, 16, and 18-26 are pending.
Claims 4-7, 14, 16 and 18-24 are withdrawn.
Claims 1, 2, 4-7, and 9 are amended
Claims 8, 11, 15 and 17 are cancelled.
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 26 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.
Claim 26, recites the phrase “the ratio of the one or more anti-nucleolin agents to the one or more PEG molecules is from 1:3 to less than 12:0”. This is indefinite because the ratio of “12:0” implies that there are no PEG molecules present which contradicts the “one or more PEG molecules” that is stated in both claim 26 and independent claim 1.
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 1-3, 9, 10, 12, and 13 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2 and 4 of U.S. Patent No. 9452219 B2 in view of HWANG (A Nucleolin-Targeted Multimodal Nanoparticle Imaging Probe for Tracking Cancer Cells Using an Aptamer. The Journal of Nuclear Medicine. 2010.).
The patent teaches a composition, comprising an anti-nucleolin agent conjugated to nanoparticles, wherein the nanoparticles comprise gold and wherein the anti-nucleolin agent is AS1411 (SEQ ID NO: 10) (claim 1), further comprising a cyanine dye (claim 2) and wherein the nanoparticles have an average diameter of 1 to 20 nm (claim 4).
The patent does not teach conjugating polyethylene glycol (PEG) to the nanoparticles.
HWANG teaches a nanoparticle that is conjugated to PEG and an anti-nucleolin agent, such as AS1411 that is also conjugated to the nanoparticle independently (figure 1). The PEG is used to reduce nonspecific uptake of nanoparticles by the mononuclear phagocytic system (page 104, paragraph 3), which improves biodistribution of the nanoparticles (page 104, paragraph 5).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate conjugating PEG to the nanoparticles with AS1411. The person of ordinary skill in the art would have been motivated to make those modifications, because PEG reduce nonspecific uptake within the body which improves biodistribution and reasonably would have expected success because both references are in the same field of endeavor, such as pharmaceutical compositions comprising nanoparticles and AS1411.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1, 2, 9, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by LI (Gadolinium Oxide Nanoparticles and Aptamer-Functionalized Silver Nanoclusters-Based Multimodal Molecular Imaging Nanoprobe for Optical/Magnetic Resonance Cancer Cell Imaging. Analytical Chemistry. 2014.).
Regarding claim 1, LI teaches a composition comprising an anti-nucleolin agent, such as AS1411 (abstract) and PEG conjugated to nanoparticles (abstract). The nanoparticles have a diameter of 20 nm (Page 11308, paragraph 8 and figure 1b).
Note: Instant claim 1 only states that the anti-nucleolin agent and PEG must be conjugated to the nanoparticle. It does not state the particular way the two components must be conjugated, such as “directly” or “independently”. Therefore LI teaching a nanoparticle conjugated to PEG and the anti-nucleolin agent conjugated to the nanoparticle via the PEG (abstract) reads on the one or more anti-nucleolin agents are conjugated to the nanoparticle.
Regarding claim 2, LI teaches the nanoparticles comprise Gadolinium(III) oxide, which reads on an inorganic material selected from the group consisting of metals, elements and oxides.
Regarding claim 9, LI teaches using AS1411.
Regarding claim 12, LI teaches a diameter of 20 nm.
Claims 1, 2 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by HWANG (A Nucleolin-Targeted Multimodal Nanoparticle Imaging Probe for Tracking Cancer Cells Using an Aptamer. The Journal of Nuclear Medicine. 2010.).
Regarding claim 1, HWANG teaches a nanoparticle that is conjugated to PEG and an anti-nucleolin agent, such as AS1411 that is also conjugated to the nanoparticle independently (figure 1) with a size/diameter of 50 nm (page 99, paragraph 5).
Regarding claim 2, HWANG teaches the nanoparticle comprises cobalt–ferrite, which reads on a metal.
Regarding 9, HWANG teaches using AS1411 (figure 1).
Additional disclosures: HWANG teaches further adding a dye, such as rhodamine B isothiocyanate fluorescence dye (page 100, paragraph 7).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1, 2, 3, 9, 10, 12, 13 and 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over MALIK (WO 2016/179394) in view of HWANG (A Nucleolin-Targeted Multimodal Nanoparticle Imaging Probe for Tracking Cancer Cells Using an Aptamer. The Journal of Nuclear Medicine. 2010.).
Regarding claim 1, MALIK teaches a composition, comprising gold nanoparticles (page 22, paragraph 4) that are conjugated to AS1411 (page 22, paragraph 4), which is an anti-nucleolin agent. The nanoparticles are 5-15 nm (page 22, paragraph 4). Polyethylene glycols can be added to the composition (page 19, paragraph 2). The AS1411 is used for anticancer activity (page 22, paragraph 4).
Regarding claim 2, 3 and 13, MALIK teaches using gold (page 22, paragraph 4), which reads on a metal.
Regarding claim 9, MALIK teaches using AS1411 (page 22, paragraph 4).
Regarding claim 10, MALIK teaches the nanoparticles further comprise a cyanine dye (page 24, paragraph 2).
Regarding claim 12, MALIK teaches the nanoparticles are 5-15 nm (page 22, paragraph 4).
Regarding claim 25, MALIK teaches the AS1411 is conjugated to the nanoparticle through a thiol (page 23, paragraph 6).
MALIK does not teach conjugating polyethylene glycol (PEG) to the nanoparticles or the ratio of anti-nucleolin agent to PEG.
HWANG teaches a nanoparticle that is conjugated to PEG and an anti-nucleolin agent, such as AS1411 that is also conjugated to the nanoparticle independently (figure 1). The PEG is used to reduce nonspecific uptake of nanoparticles by the mononuclear phagocytic system (page 104, paragraph 3), which improves biodistribution of the nanoparticles (page 104, paragraph 5).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate conjugating PEG to the nanoparticles with AS1411. The person of ordinary skill in the art would have been motivated to make those modifications, because PEG reduce nonspecific uptake within the body which improves biodistribution and reasonably would have expected success because both references are in the same field of endeavor, such as pharmaceutical compositions comprising nanoparticles and AS1411.
Regarding claim 26, the reference does not specifically teach the ratio of the anti-nucleolin agent to PEG molecule as claimed by the Applicant. The ratio of the anti-nucleolin agent to PEG molecule is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal ratio of the anti-nucleolin agent to PEG molecule in order to best achieve desired results, such as having the appropriate amount of AS1411 to achieve the therapeutic anticancer effect desired and having the appropriate amount of PEG to reduce nonspecific update to improve biodistribution. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the ratio of the anti-nucleolin agent to PEG molecule would have been obvious at the time of Applicant’s invention.
Response to Arguments
Applicant argues, Applicant respectfully submits that a prima facie case of obviousness has not been established for at least the reason that the rejection has not provided a clear articulation of the reason(s) why the claimed invention would have been obvious. For example, the rejection includes only four sentences in the rejection of seven claims, and the rejection does not address all of the limitations of the seven claims.
Examiner does not find this argument persuasive because claims 1-3, 9, 10, 12, and 13 are rejected as being obvious under the double patenting rejection, wherein if one claim is rejected under ODP, then a terminal disclaimer is required for the whole application.
Applicant argues, the rejection asserts that Li discloses Applicant's claimed nanoparticle composition, where Applicant's nanoparticle is conjugated with an anti-nucleolin agent and a PEG. However, Li's conjugated particle is not the same as Applicant's conjugated nanoparticle. Specifically, the anti-nucleolin agent in Li is attached to the PEG and the PEG is then attached to the nanoparticle (See, e.g., the Abstract, the figure in the Abstract, and the paragraph bridging pp. 11307-11308). In contrast, Applicant's claims require that each of the PEG and the anti-nucleolin agent are separately conjugated to the nanoparticle (See, e.g., Figure 1 and [0043]); this aspect is further clarified by Applicant's claim amendments. As such, Li does not disclose Applicant's claimed conjugated nanoparticle.
Examiner does not find this argument persuasive because as discussed above, LI teaches a composition comprising an anti-nucleolin agent, such as AS1411 (abstract) and PEG conjugated to nanoparticles (abstract). The nanoparticles have a diameter of 20 nm (Page 11308, paragraph 8 and figure 1b). Note: Instant claim 1 only states that the anti-nucleolin agent and PEG must be conjugated to the nanoparticle. It does not state the particular way the two components must be conjugated, such as “directly” or “independently”. Therefore LI teaching a nanoparticle conjugated to PEG and the anti-nucleolin agent conjugated to the nanoparticle via the PEG (abstract) reads on the one or more anti-nucleolin agents are conjugated to the nanoparticle.
Applicant argues, Applicant's show that using PEG increases effectiveness in vitro (see, paras [83][90]). Suk only discusses influences of PEG on in vivo efficacy by decreasing opsonization and phagocytosis, and by prolonging systemic circulation time; these are not relevant to in vitro effectiveness. Thus, having an increased effectiveness by using PEG, as claimed, provides an unexpected property and result in vitro, and the rejection does not have a showing of reasonable expectation of success for this property. Applicant respectfully submits that the rejection provides insufficient rationale as to why one of ordinary skill in the art would modify the teachings of the cited art to result in Applicant's claims, especially when Applicant has shown unexpected results and the cited art does not provide any indication of a reasonable expectation of success of such unexpected results.
Examiner does not find this argument persuasive because unexpected results must be supported by factual evidence, and attorney argument is not evidence. See In re Pearson, 494 F.2d 1399,1405 (CCPA 1974). The cited paragraphs of the Specification detail benefits of the claimed method but do not state that unexpected results were obtained. Thus, Applicant has not provided evidence that unexpectedly superior results were obtained with the claimed method. "Mere improvement in properties does not always suffice to show unexpected results." In re Soni, 54 F.3d 746,751 (Fed. Cir. 1995).
In the instant case, HWANG teaches a nanoparticle that is conjugated to PEG and an anti-nucleolin agent, such as AS1411 that is also conjugated to the nanoparticle independently (figure 1). The PEG is used to reduce nonspecific uptake of nanoparticles by the mononuclear phagocytic system (page 104, paragraph 3), which improves biodistribution of the nanoparticles (page 104, paragraph 5).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate conjugating PEG to the nanoparticles with AS1411. The person of ordinary skill in the art would have been motivated to make those modifications, because PEG reduce nonspecific uptake within the body which improves biodistribution and reasonably would have expected success because both references are in the same field of endeavor, such as pharmaceutical compositions comprising nanoparticles and AS1411.
Furthermore, applicant’s claims are not directly pointed to either in vitro or in vivo, but rather to the composition by itself.
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 SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
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, MICHAEL HARTLEY can be reached at (571) 272-0616. 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.
/S.L.M./ Examiner, Art Unit 1618 /JAKE M VU/Primary Examiner, Art Unit 1618