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 .
Election/Restrictions
To summarize, the applicant elected Group IV and the species where the cell proliferative disorder that is treated is cancers with RAS mutations and lymph node metastases and the treatment regimen administers a composition comprising silver atomic quantum clusters (AQCs) consisting of 5 zero valent silver atoms that is devoid of an additional antineoplastic drug, other active compounds, and is conducted in the absence of radiation therapy, with traverse.
In regards to limitations of claims 37 and 38, the election of species was expanded to include compositions that also administer an additional antineoplastic agent and non-metastatic cancers.
Claims 1-23 and 28-31, are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions and species, there being no allowable generic or linking claim.
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.
Claims 26-27, 33-36, and 40-44 are rejected under 35 U.S.C. 103 as being unpatentable over Lopez Quintela C (US Patent No. 9,421,610 – previously cited) in view of Buceta et al. (previously cited), Porto B (Advanced Materials 2018 30: 1801317:1-8 –previously cited), Ligresti et al. (previously cited), Jin et al. (previously cited), and Lien et al. (previously cited) as evidenced by Lopez Quintela B (EP 1914196 – previously cited) and Lopez Quintela D (WO 2012/059572 - previously cited).
Lopez Quintela C teach the administration of just a population of more than 2 to less than 27 metal atom AQCs to treat breast cancer that are also recited as silver atom AQCs with 2 to 5 atoms (see claims 1-4 and 17). Size population based tests showed that a composition of 2 to 5 silver atom AQCs was antiproliferative against breast cancer cells and that efficacy appeared to increase with size across tested populations (see column 13 lines 10-15 and figure 15). Lopez Quintela B details this same example of silver 2-5 atom AQCs as cytostatic against breast cancer cells (see paragraph 78). Lopez Quintela D then expand upon the use of these AQCs and describe them as zero valent (see page 3 lines 27-32 and page 4 lines 6-12; instant claims 26, 33-34 and 42). Moreover, Lopez Quintela C explicitly claim the 2-5 atom AQCs, suggesting greater attention on this subset in the population they disclose (see claim 2). The distribution of 2, 3, 4, and 5 atom silver AQCs in the population of Lopez Quintela C is not detailed.
Buceta et al. liken 3 atom silver AQCs to known DNA intercalating compounds such as doxorubicin because of its ability to intercalate into DNA and distort its structure (see page 7614 first column last paragraph and second column first paragraph). Measurement of the cluster size yields dimensions of 300 pm (see page 7613 first column first full paragraph). A smaller sized 2 atom silver AQC did not intercalate into the DNA (see (see page 7615 second column first full paragraph). They further point to its expected utility as a cancer therapeutic because of its intercalation ability (see page 7615 second column last paragraph). However, Porto B teach that in treating lung cancer cells, the 3 atom silver AQCs were not effective alone as anti-proliferative agents, but instead were able to enhance the activity of a co-administered antiproliferative agent (see page 2 second column last partial paragraph and figure 4). These findings suggest that the 2 and 3 atom AQCs in the 2-5 atom silver AQC population of Lopez Quintela C are not the main actors in its antiproliferative effect.
Ligresti et al. teach doxorubicin as a potent anti-neoplastic agent that treats breast cancer in patients (see page 454 first column second-third full paragraphs).
Jin et al. teach doxorubicin as retaining the ability to function as an antiproliferative active against H-Ras mutant breast cancer as compared to wild type (see page 186 first column second-third paragraphs and second column last partial paragraph and figure 2).
Lien et al. teach the utility of doxorubicin in liposomal carriers as a treatment against metastatic breast cancer in patients that avoids undesired effects on non-target tissue that are associated with its unencapsulated counterpart when administered after a treatment when non-metastatic (see abstract page 7320 first column first partial paragraph-first full paragraph). They further detail their effectiveness in reducing lymph node metastasis (see table I).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat a patient with H-RAS mutant breast cancer that is metastatic and found in the lymph nodes with the zero valent silver 2-5 atom AQCs of Lopez Quintela C. This choice would have been obvious because they teach breast cancer treatment generally with this composition. The ability of a known broadly effective breast cancer treatment to extend into H-RAS mutated subgroups is taught by Ligresti et al. and Jin et al. Further, Lien et al. teach the efficacy of such compounds against metastatic breast cancer as well as lymph node metastatic cancer. Thus there would have been a reasonable expectation of success that the zero valent silver 2-5 atom AQCs of Lopez Quintela C also would be able to treat this variety of breast cancer. Further, Lopez Quintela C suggest the efficacy of the population of AQCs is size dependent, where a larger size was superior. Buceta and Porto B also suggest larger sizes within the 2-5 atom clusters as the likely actors in its antiproliferative effects due to the absence of such activity in the smaller sizes. Thus a 2-5 atom population of AQCs that has a larger proportion of the larger sized clusters would also have been obvious. Experimentation that manipulates this parameter would also have been obvious and collectively would meet the proportion instantly claimed. There is currently no evidence that the claimed proportion of different sized clusters is critical to functionality. Therefore claims 26-27, 33-36, and 40-44 are obvious over Lopez Quintela C in view of Buceta et al., Porto B, Ligresti et al., Jin et al., and Lien et al. as evidenced by Lopez Quintela B and Lopez Quintela D.
Claims 26-27, 32-36, and 39-44 are rejected under 35 U.S.C. 103 as being unpatentable over Lopez Quintela C in view of Buceta et al., Porto B, Ligresti et al., Jin et al., and Lien et al. as evidenced by Lopez Quintela B and Lopez Quintela D as applied to claims 26-27, 33-36, and 40-44 above, and further in view of Palama et al. (previously cited).
Lopez Quintela C in view of Buceta et al., Porto B, Ligresti et al., Jin et al., and Lien et al. as evidenced by Lopez Quintela B and Lopez Quintela D render obvious the limitations of instant claims 26-27, 33-36, and 40-44 where a nanoparticle sized collection of zero valent silver AQCs is administered to treat cancer. A carrier and administration route are not explicitly detailed
Palama et al. teach silver nanoparticle based cancer treatments where particle sizes that are envisioned range from 0.1 to 400 nm (see page 6 lines 6-7). They detail their delivery intravenously in the presence of a carrier (see page 7 lines 15-18).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer the silver AQCs of the modified Lopez Quintela C method in a carrier via an intravenous route because it was a known and utilized ways to delivery similarly sized silver particles. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement. Therefore claims 26-27, 32-36, and 39-44 are obvious over Lopez Quintela C in view of Buceta et al., Porto B, Ligresti et al., Jin et al., Lien et al., and Palama et al. as evidenced by Lopez Quintela B and Lopez Quintela D.
Claims 26, 32-37, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Lopez Quintela D in view of Buceta et al., Kiessling et al. (previously cited), and Chapman et al. (previously cited).
Lopez Quintela D teach treating cell proliferative disorders including several cancers by administering to a patient zero valent AQCs with 2 to 25 transition metal atoms with a carrier and an antineoplastic agent where the AQCs enhance the effectiveness of the antineoplastic agent (see page 4 lines 1-23). A preferred population of 2 to 12 and 2 to 5 is also detailed (see page 8 lines 1-2 and claim 2). Silver is one of two most preferred metals (see page 8 lines 19-20) Particular classes of compounds are taught to be enhanced and particular cancers are envisioned as being treated (see page 9 line 29-page 10 line 4 and claims 7 and 10). The clusters of interest are preferably less than 0.5 nm, preferably 0.25 to 0.4 nm, due to their ability to intercalate into DNA at this size (see page 6 line 21-23 and line 28-page 7 line 9). Carriers are taught for the preparation as is intravenous administration (see page 10 lines 9-21) Neuroblastoma is explicitly envisioned as a treated cancer and kinase inhibitors are envisioned antineoplastic agents (see claims 7 and 10). A particular patient subpopulation is not detailed.
Buceta et al. liken 3 atom silver AQCs to known DNA intercalating compounds such as doxorubicin because of its ability to intercalate into DNA and distort its structure (see page 7614 first column last paragraph and second column first paragraph). Measurement of the cluster size yields dimensions of 300 pm (0.3 nm) (see page 7613 first column first full paragraph). A smaller sized 2 atom silver AQC did not intercalate into the DNA (see (see page 7615 second column first full paragraph).
Kiessling et al. teach treating NRAS mutant neuroblastoma by administering a combination of everolimus and selumetinib (see abstract, page 4 first full paragraph and figure 2). Everolimus is a kinase inhibitor (see Chapman et al. page 862 first column first point).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat NRAS mutant neuroblastoma with the combination of everolimus and selumetinib taught by Kiessling et al. along with the silver AQCs of Lopez Quintela D. This provides a known combination of an envisioned anti-neoplastic agent and a cancer to treat amongst those of Lopez Quintela D. It additionally would have been obvious to select a population slightly larger in size than the 3 atom size of Buceta et al., given the size desired by Lopez Quintela D is slightly larger than their 300 pm size. The result is a population of zero valent AQCS with a number of atoms slightly more than 3 which reasonably overlaps in scope with the populations instantly claimed. Administration in a carrier and intravenous route would follow based upon Lopez Quintela D. There is no evidence of the criticality of the instantly claimed distribution of silver AQC sizes when employed in concert with additional neoplastic agent(s) against neuroblastoma. Therefore claims 26, 32-37, and 39 are obvious over Lopez Quintela D in view of Buceta et al., Kiessling et al., and Chapman et al.
Claims 26, 32-36, and 38-39 are rejected under 35 U.S.C. 103 as being unpatentable over Lopez Quintela D in view of Buceta et al., and Lin et al. (previously cited).
Lopez Quintela D teach treating several cancers by administering to a patient zero valent AQCs with 2 to 25 transition metal atoms with a carrier and an antineoplastic agent where the AQCs enhance the effectiveness of the antineoplastic agent (see page 4 lines 1-23). A preferred population of 2 to 12 is also detailed (see page 8 lines 1-2). Silver is one of two most preferred metals (see page 8 lines 19-20) Particular classes of compound are taught to be enhanced and particular cancers are envisioned as being treated (see page 9 line 29-page 10 line 4 and claims 7 and 10). The clusters of interest are preferably less than 0.5 nm, preferably 0.25 to 0.4 nm, due to their ability to intercalate into DNA at this size (see page 6 line 21-23 and line 28-page 7 line 9). Carriers are taught for the preparation as is intravenous administration (see page 10 lines 9-21) Alkylating agents are preferred antineoplastic agents to pair with the AQCs and oxaliplatin is named (see page 13 lines 17-24 and page 14 lines 20). A particular patient subpopulation is not detailed.
Buceta et al. liken 3 atom silver AQCs to known DNA intercalating compounds such as doxorubicin because of its ability to intercalate into DNA and distort and unwind its structure (see page 7614 first column last paragraph and second column first paragraph). Measurement of the cluster size yields dimensions of 300 pm (0.3 nm) (see page 7613 first column first full paragraph). A smaller sized 2 atom silver AQC did not intercalate into the DNA (see (see page 7615 second column first full paragraph).
Lin et al. teach treatment with oxaliplatin as effective against KRAS mutated colorectal cancer in extending progression free survival time over other therapies (see abstract, page 364 first column, page 368 first column second paragraph, and figure 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat KRAS mutant colorectal cancer with the combination of oxaliplatin with the silver AQCs of Lopez Quintela D. Thus choice is a known antineoplastic also envisioned by Lopez Quintela D which is known to be effective against this particular variety of cancer in light of Lin et al. It additionally would have been obvious to select a population slightly larger in size than the 3 atom size of Buceta et al., given the size desired by Lopez Quintela D is slightly larger than their 300 pm size. The result is a population of zero valent AQCs with a number of atoms slightly more than 3 which reasonably overlaps in scope with the populations instantly claimed. Further, administration in a carrier and intravenous route would follow based upon Lopez Quintela D. There is no evidence of the criticality of the instantly claimed distribution of silver AQC sizes when employed in concert with additional neoplastic agent(s) against colorectal cancer. Therefore claims 26, 32-36, and 38-39 are obvious over Lopez Quintela D in view of Buceta et al. and Lin et al.
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.
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Claims 26-27, 33-36, and 40-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of U.S. Patent No. 9,421,610 in view of Lopez Quintela B, Buceta et al., Porto B, Ligresti et al., Jin et al., and Lien et al. as evidenced by Lopez Quintela D.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim treating a cell proliferative disorder with silver AQCs where the patent claim recite breast cancer specifically. The patented claim recites the number of atoms to be from more than 2 to less than 27.
Lopez Quintela B teach the administration AQCS with 2 to 5 metal atoms as a cytostatic agent and as a drug for the treatment of cancer (see claims 3 and 31-32). Silver is a named metal (see claim 5). Size population based tests showed that a composition of 2 to 5 silver atom AQCs was cytotoxic against breast cancer cells and that larger sizes were more efficacious (see paragraph 78 and figure 15). Lopez Quintela D then describe expanding upon the use of these AQCs and describe them as zero valent (see page 3 lines 27-32 and page 4 lines 6-12). Thus the 2 to 5 silver atom AQCs qualify as a composition comprising greater than 50% of the AQCs with silver atoms and as a composition of 2 to 5 atom zero valent silver AQCs (see instant claims 26, 33-34 and 42).
Buceta et al. liken 3 atom silver AQCs to known DNA intercalating compounds such as doxorubicin because of its ability to intercalate into DNA and distort its structure (see page 7614 first column last paragraph and second column first paragraph). Measurement of the cluster size yields dimensions of 300 pm (see page 7613 first column first full paragraph). A smaller sized 2 atom silver AQC did not intercalate into the DNA (see (see page 7615 second column first full paragraph). They further point to its expected utility as a cancer therapeutic because of its intercalation ability (see page 7615 second column last paragraph). However, Porto B teach that in treating lung cancer cells, the 3 atom silver AQCs were not effective alone as anti-proliferative agents, but instead were able to enhance the activity of a co-administered antiproliferative agent (see page 2 second column last partial paragraph and figure 4). These findings suggest that the 2 and 3 atom AQCs in the 2-5 atom silver AQC population of Lopez Quintela B are not the main actors in its antiproliferative effect.
Ligresti et al. teach doxorubicin as a potent DNA intercalating anti-neoplastic agent that treats breast cancer in patients (see page 454 fist column second-third full paragraphs).
Jin et al. teach doxorubicin as retaining a reduced, but still present level of apoptosis inducing capabilities in H-Ras mutant breast cancer (see page 186 first column second-third paragraphs and second column last partial paragraph and figure 2)
Lien et al. teach the utility of doxorubicin in liposomal carriers as a treatment against metastatic breast cancer in patients that avoids undesired effects on non-target tissue that are associated with its unencapsulated counterpart when administered after a treatment when non-metastatic (see abstract page 7320 first column first partial paragraph-first full paragraph). They further detail their effectiveness in reducing lymph node metastasis (see table I).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of patented claims where the breast cancer is H-Ras mutant breast cancer that is metastatic and found in the lymph nodes and the AQCs are the zero valent silver 2-5 atom AQCs of Lopez Quintela B. This choice would have been obvious because they teach breast cancer treatment generally with this composition. In addition, Buceta et al. liken its mechanism of action to that of doxorubicin which is efficacious against metastatic breast cancer and lymph node metastasis. Lien et al. and Jin et al. teach the efficacy of doxorubicin against H-Ras mutant metastatic breast cancer as well as lymph node metastatic cancer. Thus there would have been a reasonable expectation of success that the zero valent silver 2-5 atom AQCs of Lopez Quintela B and embraced by the patented claim also would be able to treat this variety of breast cancer. Further, Lopez Quintela B suggest the efficacy of the population of AQCs is size dependent, where a larger size was superior. Buceta and Porto B also suggest larger sizes within the 2-5 atom clusters as the likely actors in its antiproliferative effects due to the absence of such activity in the smaller sizes. Thus a 2-5 atom population of AQCs that has a larger proportion of the larger sized clusters would also have been obvious. Experimentation that manipulates this parameter would also have been obvious and collectively would meet the proportion instantly claimed. There is currently no evidence that the claimed proportion of different sized clusters is critical to functionality. Therefore claims 26-27, 33-36, and 40-44 are obvious over claim 17 of U.S. Patent No. 9,421,610 in view of Lopez Quintela B, Buceta et al., Porto B, Ligresti et al., Jin et al., and Lien et al. as evidenced by Lopez Quintela D.
Claims 26-27, 32-36, and 39-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 17 of U.S. Patent No. 9,421,610 in view of Lopez Quintela B, Buceta et al., Porto B, Ligresti et al., Jin et al., and Lien et al. as evidenced by Lopez Quintela D as applied to claims 26-27, 33-36, and 40-44 above, and further in view of Palama et al.
Claim 17 of U.S. Patent No. 9,421,610 in view of Lopez Quintela B, Buceta et al., Porto B, Ligresti et al., Jin et al., and Lien et al. as evidenced by Lopez Quintela D render obvious the limitations of instant claims 26-27, 33-36, and 40-44 where a nanoparticle sized collection of zero valent silver AQCs is administered to treat cancer. A carrier and administration route are not explicitly detailed
Palama et al. teach silver nanoparticle based cancer treatments where particle sizes that are envisioned range from 0.1 to 400 nm (see page 6 lines 6-7). They detail their delivery intravenously in the presence of a carrier (see page 7 lines 15-18).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer the silver AQCs of the modified method of the patented claim in a carrier via an intravenous route because both were known and utilized ways to delivery similarly sized silver particles. This modification would have been obvious as the application of the same technique to a similar product in order to yield the same improvement. Therefore claims 26-27, 32-36, and 39-44 are obvious over claim 17 of U.S. Patent No. 9,421,610 in view of Lopez Quintela B, Buceta et al., Porto B, Ligresti et al., Jin et al., Lien et al. and Palama et al. as evidenced by Lopez Quintela D.
Response to Arguments
Applicant's arguments filed July 21, 2025 have been fully considered. In light of the amendment, the rejection under 35 USC 112(b) is hereby withdrawn. The arguments against the remaining rejections are unpersuasive.
Regarding the rejections under 35 USC 103:
The applicant argues that Lopez Quintela B, Lopez Quintela C, Lopez Quintela D, Buceta et al., and Porto B teach away from AQCs with more than 50 mol% of 5 zero valent metal transition atoms. These references do not teach away from the 5 zero valent silver atom AQCs or make any disparaging statement regarding their use. Instead they teach mixed populations of AQCs with a range of number of atoms that include the 5 zero valent silver atom AQCs. Both Lopez Quintela B and Lopez Quintela C teach a 2 to 5 zero valent silver atom AQC mixture that is “clearly cytostatic” against breast cancer cells and that the impact tended to increase with the number of atoms where a larger atom number population was stronger (see example 6 in both). Lopez Quintela D also teaches a preferred range of between 2 and 5 zero valent atom AQCs, not just the 2 to 3 atom range the applicant notes. Buceta et al. and Porto B point to the 2 atom and 3 atom zero valent silver AQCs not directly acting as not antiproliferative agents, but note that the that 3 atom variety is large enough to intercalate and distort cellular DNA like doxorubicin, which suggests that the 4 atom and/or 5 atom silver AQCs in the mixed population of Lopez Quintela C are the antiproliferative members whose size lets them impact proliferation. There is no evidence that a greater that 50 mol% proportion of 5 zero valent atom silver AQCs is critical to their antiproliferative impact (treatment) on cancers. Thus there is a reasonable expectation of success for a population of zero valent silver AQCs enriched in 4 and/or 5 atom varieties to function in this way. The applicant’s implied criticality can be demonstrated with a showing that the claimed proportions of 5 zero valent atom AQCs is unexpectedly superior to other proportions. Current evidence shows a proof of concept that the 5 zero valent atom silver AQCs functions as an antiproliferative against a variety of wild type and RAS mutated cancers, but does not speak to the importance of the proportion of clusters with 5 atoms.
The applicant also argues that Jin et al. teach that RAS mutations confer drug resistance which teaches away from the utility of the silver AQCs against RAS mutated breast cancer. While less effective, Jin et al. showed that doxorubicin still induced cell death (treated) in RAS mutated breast cancer cells. The instant claims recite treating various cell proliferative conditions and do not require any particular degree of efficacy. Thus it would have been reasonable to expect that the 5 zero valent silver atom AQCs would also be able to yield a degree of treatment for this same cancer.
The applicant additionally notes that Lin et al. teach that KRAS mutations in colorectal cancer predict a poor response to epidermal growth factor receptor (EGFR) monoclonal antibody treatment and reduce the number of treatment options that are available and the need for additional treatments. They suggest that this teaching points to unpredictability in the art. While this work suggest that the efficacy of a treatment with a protein binding based mechanism like that the EGFR antibody relies upon would be unpredictable, the 5 zero valent atom silver AQCs are taught to act via a physical mechanism and in concert with an additional neoplastic agent. Lin et al. teach that another compound that also acts via physical mechanism is effective in these mutated cancers. Thus the pairing of this compound with the 5 zero valent silver atom AQCs would also be expected to treat the cancer, as the rejection reliant on Lin et al. details.
Regarding the double patenting rejections:
The applicant’s reiteration of the argument against the rejections under 35 USC 103 is noted and the response is similarly reiterated.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/CARALYNNE E HELM/ Examiner, Art Unit 1615
/MELISSA S MERCIER/ Primary Examiner, Art Unit 1615