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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/1/2025 has been entered.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 10/23/2024 is acknowledged.
Claim 13-33 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II and nonelected species, inhibiting the growth of cancer cells, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/23/2024.
Status of Claims
Withdrawn: 13-33
Cancelled: 2, 34
Examined Herein: 1, 3-12
Priority
Priority to PRO 62/830,344 filed on 4/5/2019 and PCT/US2020/026947 filed on 4/6/2020 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/16/2023 is in compliance with the
provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the
examiner.
Drawings
The drawings filed on 10/1/2021 are accepted.
Withdrawn Rejections
All rejections of claim 2 and 34 are hereby withdrawn; its cancellation moots the rejections.
The rejection of claims 1, 3-4, 7, and 12 under 35 U.S.C. 102(a)(1) over Cruz is hereby withdrawn in view of Applicant’s amendments to claim 1, which now recites the limitation “wherein the selenium nanoparticles have an average diameter in the range from about 50 to 110 nm” and persuasive arguments that Cremonini does not teach this limitation. [Reply 11/1/2025, Page 7]
The rejection of claims 1, 3, 5, 7, and 12 under 35 U.S.C. 102(a)(1) as anticipated by, or, in the alternative, under 35 U.S.C. 103 as obvious over Cremonini is hereby withdrawn in view of Applicant’s amendments to claim 1, which now recites the limitation “wherein the selenium nanoparticles have an average diameter in the range from about 50 to 110 nm” and persuasive arguments that Cremonini does not teach this limitation. [Reply 11/1/2025, Page 7]
Claim Interpretation
Claim 1 recites the limitation “wherein the selenium nanoparticles have an average diameter in the range from about 50 to about 110 nm.” The specification defines the term “about” as ± 10%. [Specification, Page 9, Line 1] Therefore, this limitation is interpreted as the selenium nanoparticles have an average diameter in the range from 45 to 121 nm.
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.
Claims 1, 3-4, 7, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Cruz (Synthesis and characterization of biogenic selenium nanoparticles with antimicrobial properties made by Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa, 2/6/2018, Journal of Biomedical Materials Research Part A, Volume 106, Issue 5, Pages 1149-1456).
With respect to claim 1, Cruz discloses a method comprising administering methicillin-resistant S. aureus selenium nanoparticles (MRSA-SeNP) to a subject, human dermal fibroblasts (HDF); [Page 1403, Col. 1, Paragraph 5-6 and Col. 2, Paragraph 1]
wherein the selenium nanoparticles are produced by a process comprising growing a drug-resistant bacterial pathogen, MRSA, in the presence of a selenium salt, sodium selenite, whereby selenium ions of the selenium salt are reduced to elemental selenium to form the selenium nanoparticles; [Page 1401, Col. 2, Paragraph 5-6 and Page 1402, Col. 1, Paragraph 1-6]
wherein the selenium nanoparticles are at least partially coated with organic molecules provided by the bacterial pathogen during the process of producing the selenium nanoparticles; [Cruz, Page 1405, Col. 1, Paragraph 4 - Col. 2, Paragraph 1 and Figure 3]
wherein the selenium nanoparticles have an average diameter of 121.4 nm. [Cruz, Page 1404, Table 1]
The limitation “a method of inhibiting the growth of a drug-resistant bacterial pathogen in a subject” recites an intended use. Only the phrase “a drug-resistant bacterial pathogen” imparts a meaningful limitation to the claim, as the body of the claim fully and intrinsically sets forth all the all of the limitations of the claimed invention and does not result in a structural difference between the claimed invention and the prior art. Therefore, the limitation “a method of inhibiting growth… in a subject” is of no significance to claim construction. MPEP 2112.02(I)
The limitations “whereby the growth of the bacterial pathogen in the subject is inhibited” and “wherein the selenium nanoparticles selectively inhibit growth of the drug-resistant bacterial pathogen, compared to inhibition by the selenium nanoparticles of growth of a non-drug-resistant form of the bacterial pathogen” recite an inherent, functional result of administering selenium nanoparticles to a subject. The selenium nanoparticles disclosed by Cruz are substantially identical to the selenium nanoparticles of instant claim 1, in that they are produced by the same process, contain the same components, and therefore yield the same nanoparticle composition. Therefore, when administered to a subject, the selenium nanoparticles disclosed by Cruz inherently possess the ability to inhibit the growth of the bacterial pathogen, MRSA, and the ability to selectively inhibit the growth of the bacterial pathogen, MRSA, compared to inhibition by the selenium nanoparticles of growth of a non-drug-resistant form of the bacterial pathogen. MPEP 2112.01(I-II) Same compositions must have the same properties.
With respect to claim 3-4, the limitations “wherein the drug-resistant bacterial pathogen is of the same species as the non-drug-resistant form of the bacterial pathogen” and “wherein both the drug-resistant and non-drug-resistant forms of the bacterial pathogen are… Staphylococcus aureus” recite an inherent, functional result of administering selenium nanoparticles to a subject. As explained above, the selenium nanoparticles disclosed by Cruz are substantially identical to the selenium nanoparticles of instant claim 1. Therefore, when administered to a subject, the selenium nanoparticles disclosed by Cruz inherently possess the ability to selectively inhibit the growth of the bacterial pathogen, MRSA, compared to inhibition by the selenium nanoparticles of growth of a non-drug-resistant form of the bacterial pathogen, including when the drug-resistant bacterial pathogen is of the same species as the non-drug-resistant form of the bacterial pathogen. MPEP 2112.01(I-II) & 211.02(I) Cruz discloses the drug-resistant bacterial pathogen is MRSA. The non-drug-resistant form of MRSA is S. aureus. MRSA and S. aureus are drug-resistant and non-drug-resistant forms are Staphylococcus aureus.
With respect to claim 7, Cruz discloses the administered selenium nanoparticles are formulated with pharmaceutically acceptable excipients including NaCl, Tris/HCl, and Milli-Q water, thus meeting the limitations of claim 7. [Page 1401, Col. 2, Paragraph 6 and Page 1402, Col. 1, Paragraph 1-5]
With respect to claim 12, the limitation “the selenium nanoparticles cause a lethal increase in reactive oxygen species in the drug-resistant bacteria” recites an inherent property of the selenium nanoparticles. As explained above, the selenium nanoparticles disclosed by Cruz are substantially identical to the selenium nanoparticles of instant claim 1. Therefore, the selenium nanoparticles disclosed by Cruz inherently possess the ability to cause a lethal increase in reactive oxygen species in the drug-resistant bacteria. MPEP 2112.01(I-II)
Cruz does not disclose the selenium nanoparticles have an average diameter in the range from 45 to 121 nm.
However, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Cruz discloses the selenium nanoparticles have an average diameter of 121.4 nm and a size distribution between 120 and 150 nm. [Page 1404, Col. 2, Paragraph 3] The diameter of the claimed selenium nanoparticles (121 nm) and the selenium nanoparticles disclosed by Cruz are so close that one skilled in the art would expect them to have the same properties. The 0.4 nm difference between the nanoparticles is virtually negligible absent any showing of unexpected results or criticality. MPEP 2144.05(I)
Modifying the method disclosed by Cruz so that selenium nanoparticles have an average diameter of about 110 nm, which corresponds with 121 nm, rather than 121.4 nm, results in the method of claim 1.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Cruz so that the selenium nanoparticles have an average diameter of about 110 nm, which corresponds with 121 nm, rather than 121.4 nm and have a reasonable expectation of success. Cruz discloses a method comprising administering methicillin-resistant S. aureus selenium nanoparticles (MRSA-SeNP) to a subject, wherein the selenium nanoparticles have an average diameter of 121.4 nm. MPEP 2144.05 (I) states that when values are so mathematically close, the difference between them are presumed to be virtually negligible. The difference between 121.4 nm and 121 nm is mathematically close (0.4 nm) and thus virtually negligible. Furthermore, Cruz discloses that the nanoparticles have a particle size distribution of 120 to 150 nm, indicating that a substantial number of nanoparticles fall within 121 nm. Therefore, it reasonable to expect the method disclosed by Cruz may be modified so that selenium nanoparticles disclosed have a diameter of 121 nm rather than 121.4 nm. One would have been motivated to do so because when values are so close, one skilled in the art would expect them to have the same properties. In the instant case, the difference between selenium nanoparticles having an average diameter of 121.4 nm versus 121 nm is negligible, so one of ordinary skill in the art would reasonably expect the aforementioned modification would yield selenium nanoparticles that have the same properties. As a result, variability may be achieved by expanding the average size of the nanoparticles, without significantly affecting the method’s overall function.
Claims 1, 3, 4, 7, and 12 are rejected under 35 U.S.C. 103 as obvious over Cruz, in view of Cremonini (Biogenic selenium nanoparticles synthesized by Stenotrophomonas maltophilia SelTE02 loose antibacterial and antibiofilm efficacy as a result of the progressive alteration of their organic coating layer, 4/10/2018, Microbial Biotechnology, 11(6):1037-1047).
With respect to claim 1, 3, 4, 7, and 12, Cruz discloses the teachings above.
Cruz further discloses the MRSA-SeNP have the ability to inhibit the growth of bacterial pathogens, S. aureus and E. coli. [Cruz Page 1407, Figure 6A and Page 1408, Figure 7A]
Cruz does not explicitly disclose the growth of the bacterial pathogen, MRSA, is inhibited by administering the selenium nanoparticles or the selenium nanoparticles selectively inhibit growth of the drug-resistant bacterial pathogen compared to inhibition by the selenium nanoparticles of growth of a non-drug-resistant form of the bacterial pathogen.
However, Cremonini discloses a method of inhibiting the growth of a drug-resistant bacterial pathogen in a subject, S. maltophilia VR10, S. maltophilia VR20, P. aeruginosa PAO1, P. aeruginosa INT, and S. aureus Mu50, the method comprising administering Stenotrophomonas maltophilia selenium nanoparticles (SeITE02-SeNP) to the subjects, whereby the growth of the bacterial pathogen in the subjects is inhibited; [Cremonini, Page 1039, Col. 2, Paragraph 1-2 and Page 1040, Table 2]
wherein the selenium nanoparticles are produced by a process comprising growing the bacterial pathogen, S. maltophilia, in the presence of a selenium salt, sodium selenite, whereby selenium ions of the selenium salt are reduced to elemental selenium to form the selenium nanoparticles; [Cremonini, Page 1044, Col. 1, Paragraph 5 – Col. 2, Paragraph 1-2]
wherein the selenium nanoparticles are at least partially coated with organic molecules provided by the bacterial pathogen during the process of producing the selenium nanoparticles; [Cremonini, Page 1038, Col. 1, Paragraph 4]
Cremonini further discloses SeITE02-SeNP inhibits the growth of the drug-resistant bacterial pathogen, S. aureus Mu 50, and selectively inhibits the growth of the drug-resistant bacterial pathogen, P. aeruginosa INT, compared to the growth of the non-drug-resistant bacterial pathogen P. aeruginosa PAO1. [Cremonini, Page 1040, Table 2]
Combining the teachings of Cruz and Cremonini results in the method of claim 1, 3-4, 7, and 12 because in view of the teachings of Cremonini, it is expected that the growth of the bacterial pathogen, MRSA, is inhibited by administering selenium nanoparticles grown in the presence of a drug-resistant bacterial pathogen and partially coated with organic molecules provided by the bacterial pathogen during the production process, and that the selenium nanoparticles selectively inhibit growth of the drug-resistant bacterial pathogen, MRSA, compared to inhibition by the selenium nanoparticles of growth of a non-drug-resistant form of the bacterial pathogen, S. aureus.
It would be obvious to one of ordinary skill in the art to combine the teachings of Cruz and Cremonini and have a reasonable expectation of success because Cruz discloses a method comprising administering MRSA-SeNP to a subject, wherein the selenium nanoparticles are produced by a process comprising growing the bacterial pathogen, MRSA, in the presence of a selenium salt and wherein the selenium nanoparticles are coated with organic molecules provided by the bacterial pathogen during the production process. Cruz further discloses the MRSA-SeNP have the ability to inhibit the growth of bacterial pathogens, S. aureus and E. coli. Similarly, Cremonini discloses a method of inhibiting the growth of a drug-resistant bacterial pathogen in a subject, P. aeruginosa PAO1, P. aeruginosa INT, and S. aureus Mu50, the method comprising administering SeITE02-SeNP to the subjects, whereby the growth of the bacterial pathogen in the subjects is inhibited. Cremonini further discloses the selenium nanoparticles are produced by a process comprising growing the bacterial pathogen, S. maltophilia, in the presence of a selenium salt and wherein the selenium nanoparticles are coated with organic molecules provided by the bacterial pathogen during the production process. Cremonini also discloses the SeITE02-SeNP inhibit the growth of the drug-resistant bacterial pathogen, S. aureus Mu 50, and selectively inhibits the growth of the drug-resistant bacterial pathogen, P. aeruginosa INT, compared to the growth of the non-drug-resistant bacterial pathogen P. aeruginosa PAO1. Thus, the disclosure Cruz establishes that the MRSA-SeNP have the ability to inhibit the growth of bacterial pathogens and the disclosure of Cremonini establishes that the growth of the drug-resistant bacterial pathogen, S. aureus Mu 50, which is a strain of MRSA, is inhibited by a selenium nanoparticle produced by the aforementioned process. Therefore, it is reasonable to expect, a drug-resistant pathogen, MRSA, would be inhibited by MRSA-SeNP. The disclosure of Cremonini also establishes that a selenium nanoparticle produced by the aforementioned process inhibits the growth of a drug-resistant bacterial pathogen, compared to the growth of the non-drug-resistant form of the bacterial pathogen. Therefore, it is reasonable to expect MRSA-SeNP would selectively inhibit growth of the drug-resistant bacterial pathogen, MRSA, compared to inhibition by the selenium nanoparticles of growth of a non-drug-resistant form of the bacterial pathogen, S. aureus. One would have been motivated to do so because the disclosure of Cremonini recognizes functional results inherently present in, or reasonably expected by, the method step of administering a selenium nanoparticle produced by the aforementioned process to a subject, that are not explicitly recognized by Cruz.
Claims 1, 3, 4, 7, 9, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Cruz, as applied to claim 1, 3, 4, 7, and 12 above, and further in view of Webster (US 9,259,005 B2, Published 2/16/2016) and Efros (US 2003/0075772 A1, Published 4/24/2003).
With respect to claim 1, Cruz discloses the teachings above.
Cruz does not disclose the selenium nanoparticles possess magnetic properties operative to collect, concentrate, organize, dissipate, or repel the nanoparticles.
However, with respect to claim 9, Webster discloses a complex comprising elemental selenium nanoparticles deposited onto a metal substrate such as nickel or cobalt. [Webster, Col. 2, Line 1-8 and Col. 9, Line 46-48, 62-66] Webster further discloses a method of inhibiting growth of bacterial pathogen by contacting the surface of the metal substrate, which is coated with the selenium nanoparticles, with a bacterial pathogen, including MRSA, thereby inhibiting the growth of said bacterial pathogen. [Webster, Col. 5, Line 39-64 and Col. 8, Line 12]
Furthermore, with respect to claim 9, Efros discloses ferromagnetic materials, like nickel and cobalt, exhibit ferromagnetism which is a property in which the internal magnetic moments spontaneously organize in a common direction and give rise to spontaneous magnetic moment.
Modifying the method disclosed by Cruz by depositing the selenium nanoparticles on a nickel or cobalt substrate, results in the method of claim 9.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Cruz by depositing the selenium nanoparticles on a nickel or cobalt substrate and have a reasonable expectation of success. Cruz discloses a method comprising administering MRSA-SeNP to a subject, wherein the selenium present in the nanoparticles is elemental selenium. Webster discloses a complex comprising elemental selenium nanoparticles deposited onto a metal substrate such as nickel or cobalt. Webster further discloses a method of inhibiting growth of bacterial pathogen by contacting the surface of the complex with a bacterial pathogen. Thus, Cruz discloses elemental selenium nanoparticles and the disclosure of Webster establishes that elemental selenium nanoparticles may be deposited onto a metal substrate such as nickel or cobalt. Therefore, it is reasonable to expect the method disclosed by Cruz may be modified by depositing the selenium nanoparticles on a nickel or cobalt substrate. It is also reasonable to expect the nickel or cobalt substrate would impart magnetic properties to the selenium nanoparticles operative to organize the nanoparticles because depositing the selenium nanoparticles on a nickel or cobalt substrate creates a complex. Efros discloses ferromagnetic materials, like nickel and cobalt, exhibit ferromagnetism. Therefore, the complex would reasonably share the magnetic properties imparted by nickel or cobalt with the selenium nanoparticles. One would have been motivated to do so reduce adhesion of bacterial pathogens on nickel or cobalt surfaces where the growth of bacterial pathogens is undesirable, like implants and/or medical devices, thereby lowering the risk of infection to patients into which the implant or medical device is placed or implanted. [Webster, Col. 1, Line 29-34 and Col. 8, Line 46-48]
Claims 1, 3, 4, 7, and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Cruz, as applied to claim 1, 3, 4, 7, and 12 above, and further in view of Cihalova (Staphylococcus aureus and MRSA Growth and Biofilm Formation after Treatment with Antibiotics and SeNPs, 10/16/2015, International Journal of Molecular Sciences, 16:24656-24672) and Fairhead (US 2004/0097705 A1, Published 5/20/2004).
With respect to claim 1, Cruz discloses the teachings above.
Cruz does not disclose the selenium nanoparticles comprise a moiety selected from the group consisting of a protein, an antibody, an oligonucleotide, and a small molecule drug or the moiety is a targeting moiety capable of targeting the selenium nanoparticles to the drug-resistant bacterial pathogen or to a cell of the subject.
However, with respect to claim 10, Cihalova discloses selenium nanoparticles comprising selenium salt, Na2SeO3·5H2O, and antibiotics, ampicillin, oxacillin, or penicillin. [Cihalova, Page 24665, Paragraph 3-4 – Page 24666, Paragraph 1-3] Ampicillin, oxacillin, and penicillin are small molecule drugs.
Cihalova further discloses administering the selenium nanoparticles to S. aureus and MRSA, which resulted in significant biofilm disruption and inhibition of the ability to form biofilm, compared to selenium nanoparticles without antibiotics and antibiotics alone. [Cihalova, Page 24661, Figure 2] Cihalova discloses this is because the selenium nanoparticles and antibiotics work synergistically to cause biofilm disruption. [Cihalova, Page 24668, Paragraph 3]
With respect to claim 11, Fairhead discloses antibiotics that have a broad spectrum of activity, such as penicillin, work by targeting bacterial cell walls. [0005]
Modifying the method disclosed by Cruz by adding a small molecule drug/targeting moiety capable of targeting the selenium nanoparticles to the drug-resistant bacterial pathogen, such as ampicillin, penicillin, or oxacillin, to the selenium nanoparticles results in the method of instant claim 10-11.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Cruz by adding a small molecule drug/targeting moiety capable of targeting the selenium nanoparticles to the drug-resistant bacterial pathogen, such as ampicillin, penicillin, or oxacillin, to the selenium nanoparticles and have a reasonable expectation of success because Cruz discloses a method comprising administering MRSA-SeNP, wherein the nanoparticles have the ability to inhibit the growth of bacterial pathogens. Cihalova discloses a method comprising administering to S. aureus and MRSA, selenium nanoparticles that comprise selenium salt and antibiotics, ampicillin, oxacillin, or penicillin. Cihalova discloses the administration resulted in significant biofilm disruption and inhibition of the ability to form biofilm, compared to selenium nanoparticles without antibiotics and antibiotics alone because selenium nanoparticles and antibiotics work synergistically to cause biofilm disruption. So, Cruz discloses selenium nanoparticles that have the ability to inhibit the growth of bacterial pathogens and Cihalova discloses selenium nanoparticles that further comprise an antibiotic have the enhanced ability to inhibit the growth of bacterial pathogens compared to selenium nanoparticles without an antibiotic. Thus, the combined teachings of Cruz and Cihalova suggest adding an antibiotic to the MRSA-SeNP would result in significantly improved inhibition of bacterial pathogens. Therefore, it is reasonable to expect the method disclosed by Cruz may be modified by adding a small molecule drug/targeting moiety capable of targeting the selenium nanoparticles to the drug-resistant bacterial pathogen, such as ampicillin, penicillin, or oxacillin, to the selenium nanoparticles. It is also reasonable to expect ampicillin, penicillin, or oxacillin would target the selenium nanoparticles to the drug-resistant bacterial pathogen because Fairhead discloses antibiotics that have a broad spectrum of activity, including ampicillin, penicillin, or oxacillin, work by targeting bacterial cell walls. Therefore, adding ampicillin, penicillin, or oxacillin to the selenium nanoparticles disclosed by Cruz, reasonably imparts a targeting capability that directs the selenium nanoparticles to bacterial cell walls. One would have been motivated to do so because Cihalova discloses selenium nanoparticles that comprise antibiotics are a tool for the treatment of bacterial infection, in the cases where antibiotics are not effective. [Cihalova, Page 24668, Paragraph 3]
Claims 1, 5, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Cremonini, and further in view of Chudobova (Comparison of the effects of silver phosphate and selenium nanoparticles on Staphylococcus aureus growth reveals potential for selenium particles to prevent infection, 12/30/2013, FEMS Microbiol Lett 351:195–201).
With respect to claim 1, Cremonini discloses a method of inhibiting the growth of a drug-resistant bacterial pathogen in a subject, S. maltophilia VR10 and S. maltophilia VR20, the method comprising administering Stenotrophomonas maltophilia (SeITE02) selenium nanoparticles (SeITE02-SeNP) to the subject, whereby the growth of the bacterial pathogen in the subject is inhibited; [Cremonini, Page 1039, Col. 2, Paragraph 1-2 and Page 1040, Table 2]
wherein the selenium nanoparticles are produced by a process comprising growing the bacterial pathogen, S. maltophilia, in the presence of a selenium salt, sodium selenite, whereby selenium ions of the selenium salt are reduced to elemental selenium to form the selenium nanoparticles; [Cremonini, Page 1044, Col. 1, Paragraph 5 – Col. 2, Paragraph 1-2]
wherein the selenium nanoparticles are at least partially coated with organic molecules provided by the bacterial pathogen during the process of producing the selenium nanoparticles; [Cremonini, Page 1038, Col. 1, Paragraph 4]
wherein the selenium nanoparticles have an average diameter of 209 nm. [Cremonini, Page 1039, Table 1]
The limitations “whereby the growth of the bacterial pathogen in the subject is inhibited” and “wherein the selenium nanoparticles selectively inhibit growth of the drug-resistant bacterial pathogen, compared to inhibition by the selenium nanoparticles of growth of a non-drug-resistant form of the bacterial pathogen” recite an inherent, functional result of administering selenium nanoparticles to a subject. The selenium nanoparticles disclosed by Cremonini are substantially identical to the selenium nanoparticles of instant claim 1, in that they are produced by the same process, contain the same components, and therefore yield the same nanoparticle composition. Therefore, the selenium nanoparticles disclosed by Cremonini inherently possess the ability to inhibit the growth of S. maltophilia, as demonstrated in Table 2, and the ability to selectively inhibit the growth of S. maltophilia, compared to inhibition by the selenium nanoparticles of growth of a non-drug-resistant form of the bacterial pathogen. MPEP 2112.01(II) & 211.02(I)
With respect to claim 5, Cremonini discloses the minimum inhibitory concentration of the selenium nanoparticles for the drug-resistant bacterial pathogen, S. maltophilia VR10, is 16 micrograms/mL or less than about 30 micrograms/mL. [Cremonini, Page 1040, Table 2, Treatment 1]
With respect to claim 7, Cremonini discloses the administered selenium nanoparticles are formulated with pharmaceutically acceptable excipients including NaCl, Tris/HCl, and deionized water. [Cremonini, Page 1044, Col. 2, Paragraph 2]
However, with respect to claim 1, Cremonini discloses antimicrobial activity of SeNPs is size dependent, with higher inhibiting effects associated with the “smallest ones,” as already reported in previous studies like Chudobova et al., 2014. [Cremonini, Page 1043, Col. 2, Paragraph 1]
Cremonini does not disclose the nanoparticles have an average diameter in the range from about 50 to 110 nm.
Chudobova discloses selenium nanoparticles that have a diameter of 50–100 nm. [Chudobova, Page 196, Col. 2, Paragraph 3] (Note: this disclosure and the size range discussed therein corresponds to the “smallest” SeNPs referenced in Cremonini as having higher inhibitory effects). Chudobova further discloses smaller nanoparticles (50-100 nm) have a greater inhibitory effect compared with larger nanoparticles (200-300 nm). [Chudobova, Page 199, Col. 2, Paragraph 1 and Page 200, Col. 1, Paragraph 3]
Modifying the method disclosed by Cremonini so that the selenium nanoparticles have an average diameter of 50-100 nm, results in the method of claim 1.
It would be obvious to one of ordinary skill in the art to modify the method disclosed by Cremonini so that the selenium nanoparticles have an average diameter of 50-100 nm and have a reasonable expectation of success. Cremonini discloses a method, wherein selenium particles with a size of 209 nm inhibit the growth of a drug-resistant bacterial pathogen S. maltophilia VR10. Cremonini further discloses antimicrobial activity of SeNPs is size dependent, with higher inhibiting effects associated with the “smallest ones,” as already reported in previous studies like Chudobova (2014). Chudobova reports selenium nanoparticles that have an average diameter of 50–100 nm. So, Cremonini discloses a method comprising selenium particles with a size of 209 nm and Chudobova discloses selenium nanoparticles may have an average diameter of 50–100 nm. Thus, the combined teachings of Cremonini and Chudobova suggest that the selenium particles in the method disclosed by Cremonini may have an average diameter of 50–100 nm. Therefore, it is reasonable to expect the method disclosed by Cremonini may be modified so that the selenium nanoparticles have a size of 50-100 nm. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. In the instant case, Chudobova discloses smaller nanoparticles (50-100 nm) have a greater inhibitory effect compared with larger nanoparticles (200-300 nm). [Chudobova, Page 200, Col. 1, Paragraph 3] Therefore, one would have been motivated by the expectation that the aforementioned modification would exhibit a greater inhibitory effect.
Response to Arguments
Applicant’s arguments filed 11/1/2025 with respect to the rejections of claim under 35 U.S.C 102(a)(1) over Cruz and Cremonini have been fully considered and are persuasive. Applicant’s arguments essentially state Cruz and Cremonini do not anticipate the claimed limitations, as amended. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made in view of the additional teachings of Cruz and Cremonini.
Applicant’s arguments drawn to allegations of unexpected results have been fully considered but they are not persuasive.
Applicant asserts “the claimed size range has the unexpected advantage of providing superior bacterial growth inhibition compared to selenium nanoparticles outside of the claimed range; the advantage of the claimed size range is unexpected in view of the combined teachings of Cruz and Cremonini.” Applicant relies on the Rule 132 Declaration by Dr. Thomas Webster to support this position. However, the declaration is insufficient to overcome the rejection of the instant claims for the reasons provided below.
Declaration
The declaration under 37 CFR 1.132 filed 11/1/2025 is insufficient to overcome the rejection of the instant claims based upon 35 U.S.C. 103 as set forth in the last Office action because the declaration is not commensurate with the claimed invention and does not provide any information not already known in the art.
Dr. Webster asserts “This data demonstrates that the smallest nanoparticle sizes, in the range of 50-110 nm as presently claimed, are more effective at bacteria inhibition than Se nanoparticles having sizes outside this range.” [AF/D.132, Page 1, Paragraph 3]
The asserted effect is already known in the art. Cremonini discloses antimicrobial activity of SeNPs is size dependent, with higher inhibiting effects associated with the smallest ones. Chudobova discloses smaller nanoparticles (50-100 nm) have a greater inhibitory effect compared with larger nanoparticles (200-300 nm). [Chudobova, Page 200, Col. 1, Paragraph 3] Moreover, Wadhwani discloses that biological source and physicochemical parameters, such as salt concentration, temperature, pH, aeration, reaction time, etc., effect the synthesis SeNPs smaller than 100 nm and reducing the size of the nanoparticles will increase their activity and render them more effective. [Wadhwani (Biogenic selenium nanoparticles: current status and future prospects, 2016, Appl Microbiol Biotechnol, 100:2555–2566), Page 2563, Col. 1, Paragraph 2]
MPEP 716.02(b) states to support allegations of unexpected results, the evidence relied upon should establish that the differences in results are in fact unexpected and unobvious. Applicant claims the claimed size range has the unexpected advantage of providing superior bacterial growth inhibition compared to selenium nanoparticles outside of the claimed range, but this effect is taught at least by Cremonini, Chudobova, and Wadhwani. Therefore, Applicant has not established that the alleged unexpected results are unexpected and significant.
Moreover, the assertions made by Dr. Webster are not fully commensurate with the claim. Claim 1 requires that the selenium nanoparticles have an average diameter of about 50-100 nm, while Dr. Webster asserts that the selenium nanoparticles must simply have a size in the range of 50-110 nm to achieve the alleged unexpected results. The declaration does not describe the criticality of the selenium nanoparticles having an average diameter within the claimed range at all.
MPEP 716.02(d) states allegations of unexpected results must be commensurate in scope with the claimed invention. Applicant has not established that the alleged unexpected results are commensurate in scope with the instant claims because the data in the declaration is drawn to selenium nanoparticles with much broader limitations than the selenium nanoparticles of the instant method.
Furthermore, the data provided by Dr. Webster does not actually establish any findings outside of the claimed range. The claimed range is about 50-110 nm, which corresponds with 45-121 nm since the specification defines the term “about” as ± 10%. [Specification, Page 9, Line 1] The bacterial density pre-synthesis data is based on SeNPs with a size of (1) 20-50 nm, (2) 50-100 nm, and (3) 100-200 nm. [AF/D.132, Page 2-3] The pH of bacterial suspension pre-synthesis data is based on SeNPs with a size of (1) 20-60 nm, (2) 50-100 nm, and (3) 100-200 nm. [AF/D.132, Page 3-4] The temperature of bacterial suspension during synthesis process data is based on SeNPs with a size of (1) 30-70 nm, (2) 70-120 nm, and (3) 120-250 nm. [AF/D.132, Page 4-5] Thus, all of the size ranges of the selenium nanoparticles tested fall within or overlap with the claimed range. Therefore, the data does not demonstrate any information with respect to selenium nanoparticles having sizes outside the claimed range.
MPEP 716.02(d)(II) states to establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. Applicant has not satisfied this burden because all of the size ranges of the selenium nanoparticles discussed in the declaration fall within or overlap with the claimed range.
Additionally, to support allegations of unexpected results MPEP 716.02(e) states Applicant must compare the claimed subject matter with the closest prior art in order to effectively rebut a prima facie case of obviousness. It is unclear whether the declaration is commensurate with the claimed subject matter because no characteristics of the selenium nanoparticles are discussed other than their size, which is expressed as a range. For example, Dr. Webster does not state whether the selenium nanoparticles were prepared according to the method of claim 1. Therefore, Applicant has not established that the declaration is drawn to the claimed subject matter or compared with the closest prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILA A CRAIG whose telephone number is (703)756-4540. The examiner can normally be reached Monday-Friday 0800-1600.
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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.
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/K.A.C./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618