DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Amendments and Remarks, filed 25 September 2025, in the matter of Application N° 18/253,694. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim 1-20 have been canceled and claims 21-33 have been newly added. Support is provided for the newly added claims.
None of the newly added claims have been further amended.
No new matter has been added.
Thus, claims 21-33 now represent all claims currently under consideration.
Information Disclosure Statement
One new Information Disclosure Statement (IDS) filed 25 September 2025, is acknowledged and has been considered.
Withdrawn Rejections
Rejection under 35 USC 112
Applicants’ amendments cancelling claims 1-20 immediately overcome the previously raised indefiniteness rejection. As such, said rejection is withdrawn.
Rejection under 35 USC 103
Applicants’ amendments cancelling claims 1-20 overcome the obviousness rejection of record. As such, said rejection is withdrawn.
New Rejections
Applicants’ amendments have necessitated the following ground of rejection:
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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. Applicants are 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 21-33 are rejected under 35 U.S.C. 103 as being unpatentable over Lux et al. (WO 2019/122790 A1; IDS/ISR reference; machine translation of record and cited) further in view of Zhou et al. (Biomaterials; March 2019) and Xu et al. (US Pre-Grant Publication Nº 2016/0166706 A1).
The instantly claimed invention is directed to method of treating cancer in a patient comprising the in vivo capture (i.e., chelation, extraction, etc.) of copper and/or iron by administering to said patient, a colloidal solution (i.e., suspension) of nanoparticles having the following formula:
[Ch1]n-PS-[Ch2]m
wherein Ch1 and Ch2 are chelating agents (e.g., DOTAGA) that are grafted to the polymer matrix (e.g., polysiloxane). Chelating agent ‘Ch1’ is either complexed or not complexed with a metal cation ‘M1,’ while ‘Ch2’ is identical to ‘Ch1’ and complexed with a metal cation having an atomic number greater than 40 (e.g., gadolinium). The nanoparticles will have a hydrodynamic diameter ranging between 1-50 nm.
Lux discloses nanoparticles that are polysiloxane-based having an average diameter of between 3 and 50 nm, comprising a chelating agent that is grafted onto the nanoparticles selected from DOTA, DAOTAGA, and DTPA. See e.g., ¶[0088].
Paragraphs [0072] and [0073] disclose that the nanoparticles advantageously possess the following formula (see also pg. 12, line 10 of the original publication):
PNG
media_image1.png
34
538
media_image1.png
Greyscale
According to ¶[0078], each of Ch1, Ch2, and Ch3 are chelating agents, which may be different or the same, linked to Si of the polysiloxanes via covalent Si-C bonds. Variables ‘a,’ ‘b,’ and ‘c’ are defined as integers ranging from between 0 and n, where ‘n’ is defined as ranging from 20-50,000. See ¶[0075] and claim 10. The sum of variables ‘a,’ ‘b,’ and ‘c’ is also less than or equal to ‘n,’ where a+b+c is preferably between 5 and 100 (e.g., 5-20). Thus, for instance, if a = 1000, b = 1, and c = 0, such a disclosure would be considered to meet the instantly claimed limitation for the “n/[n+m]” ratio ranging between 10% and 100%. Paragraph [0078] is also considered to teach the limitations of 23, whereby the instantly claimed denominator [n+m], ranges from 10-30. For instance, it is taught that the sum of a+b+c, preferably ranges between 5 and 20 and that each of a, b, and c may be defined as being between 0 and n (preferably defined as ranging between 50 and 1,000).
Regarding the limitations of claims 21 and 22, the reference teaches and suggests the metal cations that read on the “M2” variable. Paragraph [0036] discloses that the “chelating agent” means an organic group capable of complexing at least one metal cation. The metal cations disclosed as advantageously being selected from zinc, calcium, magnesium, and gadolinium, with particular focus on at least gadolinium.
Regarding the limitations of claim 22, whereby M2 is the gadolinium cation Gd3+, the Examiner maintains that the disclosure of gadolinium (Gd; atomic number = 64) by the reference meets this limitation, particularly in view of the definition set forth in the instant specification (see e.g., Spec., ¶[0038]).
The foregoing is considered to teach the “M2” limitations as recited by instant claims 21 and 22.
The average particle diameter limitations of claims 21 and 22 are also encompassed by the foregoing discussion of the average particle diameter ranging from greater than 3 nm, and preferably less than 50 nm. See e.g., ¶[0059], and [0087]. Furthermore, the claims are also read on by Example 8 and Figure 9 which disclose that the DTPA-chelated silane nanoparticles of the former are depicted by the latter as having a hydrodynamic diameter ranging between 2-8 nm, with the highest percent volume being at about 6 nm.
Claim 15, for instance, discloses the structural limitations presented in claims 21 and 29 with respect to the composition being in the form of a colloidal composition. The Examiner notes that Applicants’ instant specification refers to the composition as both a “colloidal solution” as well as a “colloidal suspension.” The reference defines the latter as meaning “a mixture of liquid and solid, insoluble, particles, which remain regularly dispersed, the particles often being sufficiently small (microscopic or nanoscopic) so that the mixture remains stable and homogeneous.” See ¶[0052]. Claim 6 also discloses a solution of chelating molecules.
Claims 14 and 18 are considered to meet the “pharmaceutical” composition limitations recited by instant claim 29. Example 2 discloses intra-tissue gadolinium by perfusion of nanoparticle solution. The implanted device is a microdialysis cannula which is placed inside the subject. See ¶[0154]-¶[0156].
Lastly, those limitations of directed to a method of treating cancer in a subject comprising the administration of the colloidal composition, are considered to be taught and suggested by the foregoing as well as claim 18. Claim 18 discloses a nanoparticle or colloidal or polymer suspension for use as a therapeutic composition in a device. Said device is disclosed as having a polymer that is grafted to at least one chelating agent capable of complexing metal cations with a complexation log for at least one of said metallic cations being greater than 10, and preferably greater than or equal to 15 (see e.g., claim 17). Claim 14 discloses that the practiced composition is brought into contact with biological fluids, such as blood, or an organ such as the brain, liver, pancreas, intestines, or lungs, or tissue, such as tumor tissue.
Thus, the Examiner submits that Lux continues to teach and suggest that the practiced composition is used to treat tumors (cancer) and would be expected to treat cancer as recited by instant claims 31 and 32, given the exemplified organs.
Where Lux appears to be immediately deficient is with respect to the limitations of claims 30 and 33, insomuch as there is not an express disclosure of using the practiced compositions to treat a “metastatic” form of cancer or other forms of cancer such as cervical, prostate, anorectal, or colorectal, respectively.
The journal article published by Zhou, however, is considered to remedy the deficiency of claim 30. Therein, Zhou provides supplemental disclosure with regard to the role that copper plays in tumor growth and metastasis, confirming copper chelation to be an effective strategy for breast cancer therapy by way of antiangiogenesis (see e.g., Abstract; Scheme 1B, pg. 88).
The Examiner acknowledges that Zhou’s polymeric nanoparticle solutions that function to chelate the copper are distinct from those disclosed by Lux. However, what is common to both disclosures, is the disclosure that copper is chelated (extracted, complexed) in order to remove it and treat tumor tissue.
Thus, what a person of ordinary skill in the art will understand from the contribution of Zhou, in combination with the disclosure of Lux is that administering the colloidal nanoparticle composition of Lux will be expected to also treat metastatic forms of cancer. Lux on its own discloses administering compositions to chelate metals such as copper and iron. Zhou reaffirms that the removal (through chelation) of copper to be an effective strategy in treating metastatic forms of cancer.
Regarding the deficiency to claim 33, the Examiner submits that evidentiary showings in the art such as provided by Xu, establish that “[e]levated copper concentration (up to 2 to 3-fold) has been observed in a wide spectrum of tumors including ovarian, breast, cervical, prostate, and leukemia and this has suggested targeted approaches using chelators in cancer treatment.” See ¶[0003]. Xu, like Lux, discloses using a polymer particle conjugate composition whose polymer backbone comprises pendant groups that function as copper chelators (see e.g., claims 1, 8, and 9).
Thus, what is understood from the combined teachings of Lux and Xu, is that a person of skill in the art would have a reasonable expectation of using the compositions prepared and administered by Lux to treat other forms of cancer as are set forth by claim 33. As the art clearly establishes copper’s angiogenic role in the formation of tumors for many different forms of cancer, the skilled artisan would thus have a reasonable expectation of treating those forms by administering a composition (e.g., a colloidal solution) such as instantly claimed to treat cancer.
Based on the combined teachings of the reference, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed nanoparticle, colloidal, and pharmaceutical compositions as well as arriving at the recited method of treating cancer. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
All claims have been rejected; no claims are allowed.
Conclusion
Applicants’ amendments 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 extension fee 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. 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 or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615