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
Applicant's election with traverse of Group I, corresponding to claims 1-17, as amended, in the reply filed on 03/09/2026 is acknowledged. The traversal is on the ground(s) that the amended claims 19 and 25 and the dependent claims of 19 now encompass Group I. This is found persuasive. However, applicant also states the traversal on the ground(s) that the examiner identified that Group II, which is related to Group I as related as a process of making and the product made, can be made through placental explants. However, the applicant states “the claims do not encompass a product that can be made using generic placental cells or other alternative starting materials. Claim 18 specifically recites coronavirus-infected eSTBs produced by the method of claim 1, thereby expressly tying the claimed product to the claimed method” and that “syncytiotrophoblasts are a specific cell type within placental tissue, and placental explants contain many different placental cell types. The Examiner's suggestion that the claimed product could be made from "placental cells" does not demonstrate that the claimed coronavirus-infected eSTBs could be produced by a materially different process. The claims are directed specifically to eSTBs produced according to the process of claim 1, not to infected placental cells generally.”
This is not found persuasive because the method of Group I recites a method of differentiating stem cells to produce cytotrophoblasts which coronavirus can than infect and replicate within the cells. As the examiner previously states, cytotrophoblasts can be isolated from placental tissue and cultured in a way that would allow coronavirus to infect and replicate within the cells.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-25 are pending, with claims 18 and 26 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Claims 1-17 and 19-25 are under consideration.
Priority
This application claims priority to US provisional application 63/402032, filed on August 29, 2022. This application also claims priority to CN application CN202210631030.7, filed on June 06, 2022.
Claim Rejections - 35 USC § 112 - Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6, 9, are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 6 and 14, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 6 recites the limitation "the derived eSTBs" in the first line of the claim. There is insufficient antecedent basis for this limitation in the claim.
The term “about” in claims 9 and 11 – 17 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 9 recites “at about 37 °C for about 2 hours”
Claim 11 recites “for about 1 day to 6 days”
Claim 12 recites “for about 1 to about 6 days”, “about 0.5x105/cm2 to about 2.0x105/cm2”, and “about 1.0x105/cm2 TSCs”
Claim 13 recites “about 0.5 weight percent”, “about 50 pM”, “about 2.5 pM”, about 2 pM”, and “about 1%”
Claim 17 recites “about 24 hours in a first culture medium”, “about 0.5x105 cells to about 2.0x105 cells per well”, “about 1 x 105 cells per well”, “about 2pM to about 10 pM”, “about 2pM to about 10 pM”, and “about 2000 cells per well to about 10,000 cells per well”
The dependent claims fail to provide additional clarity and, therefore, are also indefinite.
Regarding claims 12 and 17, the claim language “preferably” renders the limitations because it is unclear if the claims specifically require such limitation(s) or not. The dependent claims and do not add additional clarity and, therefore, are also indefinite.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1 – 5, and 11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more without significantly more. This judicial exception is not integrated into a practical application and the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because for the reasons set forth below. See MPEP § 2106 for analysis parameters.
The instant claims are drawn to a method comprising incubating cytotrophoblasts in media comprising coronavirus particles as in claims 1 – 5 and 11 which is a statutory category of invention (Step 1: YES).
The instant claims are directed to the natural phenomenon of cytotrophoblasts contacting coronaviruses and/or one or more agent. Claims 1 – 5 and 11 do not recite any specific utility in the preamble. As such, the broadest reasonable interpretation of the coronavirus medium of claims 1 – 5 and 11 encompasses coronavirus within blood. Therefore, as humans can have cytotrophoblasts that are in contact with their own bloods, the natural infection of cytotrophoblasts with coronavirus within a human is encompassed by claims 1 – 5 and 11 in addition to in vitro culture methods.
As mentioned above, the coronavirus medium can include blood. As evidenced by Mitchell et al. (NIH, Worker training Program, retrieved Oct 2020, hereinafter " Mitchell") SARS-COV-2, a coronavirus, is found in blood and can naturally infect cells and replicate within a cell (¶¶1-2). Furthermore, as evidence by Hecht et al. (modern pathology, 2020, hereinafter “Hecht”) coronavirus naturally infects cytotrophoblasts (Abstract; Figure 4).
Cytotrophoblasts are a part of the placenta and are in contact with amniotic fluid, as evidenced by Kliman (The Encyclopedia of Reproduction, 2006, hereinafter, “Kliman”). Kliman evidences that cytokines are released into the amniotic fluid after infection (Page 18-19, Section: Infection). As such recite judicial exceptions (JE) in the form of a natural phenomenon, i.e. the natural process of coronavirus incubating cytotrophoblasts in vivo with blood as the coronavirus medium (STEP 2A, Prong One: YES).
The claims are limited to the JE, and not a method of, e.g., using the JE for a particular treatment or prophylaxis, but, only a natural phenomenon. As such, the claims do not recite any additional elements that integrate the JE into a practical application (STEP 2A, Prong Two: NO).
Since the claims are limited to solely the JE, the claims do not recite any additional that amount to significantly more than the JE itself. (STEP 2B: NO).
In view of the foregoing, the instant claims do not constitute patent eligible subject matter under 35 U.S.C 101.
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.
Claim(s) 1, 2, 4, 5, and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Fahmi et al (Cell Reports Medicine, 2021, hereinafter, “Fahmi”) as evidenced by Okae et al (Cell Stem Cell, 2018, hereinafter, “Okae”)
Fahmi teaches that SARS-CoV-2 can infect and propagate in human placenta explants (Title). Fahmi teaches ex-vivo modeling of SARS-CoV-2 infection of human placenta which includes cytotrophoblasts (Summary, Graphical abstract). Exposure to SARS-CoV-2 leads to replication of the virus in tissue that expresses ACE2 and that viral RNA is found in cytotrophoblasts (Summary). It is noted that the applicant defines early synctiotrophoblasts (eSTBs) as mononucleated cells that can become synctiotrophoblasts (¶0006, 0014, 0050).
As evidenced by Okae, cytotrophoblasts are mononucleated undifferentiated and proliferative cells (Introduction, Establishment of Proliferative Human CT Cells in Culture ¶2). Furthermore, Okae evidences that cytotrophoblasts can differentiate into other trophoblasts or remain in their mononucleated form by changing different inhibitors and growth factors within the media (Establishment of Proliferative Human CT Cells in Culture ¶2).
Regarding claims 1, 2, 4 and 5, Fahmi teaches contacting placental tissue which are comprised of cytotrophoblasts with a media containing SARS-CoV-2 (Results ¶1, Figure 1).
Regarding claim 8, Fahmi teaches the quantification of the viral load of coronavirus media via a plaque assay (Section: Experimental model and subject details- Virus titration).
Regarding claim 9, Fahmi teaches the cytotrophoblasts were incubated in the coronavirus medium for 4-6 hours at 37 °C (Section: Experimental model and subject details- Virus infection). Fahmi also teaches nasal endothelial cells were incubated with coronavirus containing media for 2-3h at 37 °C (Section: Experimental model and subject details- Virus infection). It would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the optimal incubation time for different tissue types to ensure successful viral infection within the cells with a reasonable expectation of success. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Here, the instant claims encompass routine incubation time ranges for viral infection, which is readily obtained by routine optimization. Of note, the incubation times of claim 9 are similar to that of the nasal-endothelial cell. Additionally, other claims do not require a particular incubation time indicating that a particular incubation time is not critical to the method.
Regarding claim 10, Fahmi teaches the coronavirus particles were isolated from Vero E6 cells (Section: Experimental model and subject details- Viruses).
In view of the foregoing, all the claimed limitations are found in one reference and are taught to be optional variations to a ‘base’ method they exemplify. As such, the claimed invention is within the scope of Fahmi, and thus Fahmi renders the invention prima facie obvious. The rationale to support this conclusion of obviousness is that Fahmi provides a teaching, suggestion, and motivation to substitute different variables disclosed within the reference. Furthermore, there is no evidence on the record that indicates that the claimed supplement exhibits any unexpected results compared to the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 6, 7, and 12-17 are rejected under 35 U.S.C. 103 as being unpatentable over Fahmi as applied to claim 1, 2, 4, 5, and 8-10 above, and further in view of Okae as evidenced by Thermofischer (retrieved Jun/15/2021)
As discussed above, claims 1, 2, 4, 5, and 8-10 were rendered prima facie obvious by the teachings of Fahmi. The reference does not teach a using stem cell derived and differentiated cytotrophoblasts.
However, Okae teaches the derivation of human trophoblast stem cells (TSC) into different lineages (Summary). Okae teaches that these TSC can give rise to cytotrophoblasts and synctiotrophoblasts alike (Graphical abstract). Furthermore, Okae teaches that identification of markers that change throughout different stages of differentiation (Graphical abstract).
Regarding claim 6, Okae teaches isolating cytotrophoblasts as well as measuring of the cytotrophoblasts (Figure 2, Figure 2G).
Regarding claim 7, Fahim teaches measure the ACE2 mRNA levels of placental cells (Figure 1).
Regarding claim 12, Okae teaches the cytotrophoblasts are derived from human TSCs, the TSCs are cultured for 4-5 days, at an initial density of 0.5-1 x 106 per 6 well, which is 9.6cm2 per well,as evidenced by Thermofischer , resulting in 0.52-1.04 x105 per well ) (Section: Culture of TSCT, TSblast, and stromal cells, ¶1,2).
Regarding claim 13, Okae teaches that the cytotrophoblast media comprises the basal media DMEM and 1% ITS-X (Section: Culture of TSCT, TSblast, and stromal cells, ¶1).
Regarding claim 14, Okae teaches TSCs are derived from placental tissue (Section: Isolation of trophoblast and stromal cells, ¶1).
Regarding claim 15, Okae teaches identifying TSCs by the detection of an increase in KRT7, a TSC factor (Figure 3c).
Regarding claim 16, Okae teaches replating TSC 10 – 20 times (Culture of TSCT, TSblast, and stromal cells).
Regarding claim 17, Okae teaches i) culturing EPSCs in a culture medium comprising Y27632 at a concentration of 2.5um. The cells are seeded at a concentration of 0.75 x 105 cells per well of a 6 well plate (Differentiation of TSCT and TSblast cells, ¶1), ii) then a second medium comprising A83-01 (Differentiation of TSCT and TSblast cells, ¶1), and iii) a third medium for induction stem cell differentiation at a density of 2.5 x 105 (Differentiation of TSCT and TSblast cells, ¶3).
Fahmi and Okae are considered to be analogous to the claim invention because they teach the culturing of trophoblast cells. Fahmi teaches ex-vivo modeling of SARS-CoV-2 infection in human placental tissue, which includes cytotrophoblasts (Summary). Okae teaches the culturing and derivation of cytotrophoblasts through both the differentiation of blastocytes and placental stem cells (Abstract).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to study cytotrophoblasts that were differentiated from stem cells, as taught by Okae, to study coronavirus infection in the method taught by Fahmi because doing so would remove the need for invasive and time-consuming placental extraction from humans. One of ordinary skill in the art would have had a reasonable expectation of success in using a stem cell derived cytotrophoblasts to study SARS-CoV-2 infection given that using stem cell derived cytotrophoblasts to study interactions between the fetus and mother in a controlled manner is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 11 is rejected under 35 U.S.C. 103 as being unpatentable over Fahmi and Okae as applied to claim 1, 2, 4-10, and 12-17 above, and further in view of Argueta et al (iScience, May 2022, hereinafter, “Argueta”).
As discussed above, claims 1, 2, 4-10, and 12-17 were rendered prima facie obvious by the teachings of Fahmi. The reference does not teach incubating cytotrophoblasts in coronavirus media for 1 to 6 days.
However, Argueta teaches a method of studying cytotrophoblasts to understand the effect of SARS-CoV-2 infection on placental function (Summary). Argueta uses placental cultures to study the transcriptomic effects of SARS-CoV-2 and to understand the role of ACE2 with viral infection of several SARS-CoV-2 variants (Summary).
Regarding claim 11, Argueta teaches that placenta explants cultures and cell cultures can be infected with SARS-CoV-2 for up to 72 hours (Section: Infection of explants and placental clusters with pseudotyped lentivirus).
Fahmi, Okae, and Argueta are considered to be analogous to the claim invention because they teach the culturing of trophoblast cells. Fahmi teaches ex-vivo modeling of SARS-CoV-2 infection in human placental tissue, which includes cytotrophoblasts (Summary). Okae teaches the culturing and derivation of cytotrophoblasts through both the differentiation of blastocytes and placental stem cells (Abstract). Argueta teaches that placenta explants cultures and cell cultures can be infected with SARS-CoV-2 for up to 72 hours (Section: Infection of explants and placental clusters with pseudotyped lentivirus).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to study cytotrophoblasts that were differentiated from stem cells, as taught by Okae, to study coronavirus infection in the method taught by Fahmi by modifying the incubation time to up to 72 hours, as taught by Argueta, because doing so would ensure high levels of infection of SARS-CoV-2, enabling understanding of the role of the placenta during severe coronavirus infection. One of ordinary skill in the art would have had a reasonable expectation of success in incubating cytotrophoblasts for up to 72 hours to study SARS-CoV-2 infection given that this incubation time is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 19-23 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Fahmi and Okae as applied to claim 1, 2, 4-10, and 12-17 above, and further in view of Choi et al (Antiviral Res, 2020, hereinafter, “Choi”) and Saroyo et al (infectious disease reports, 2021, hereinafter, “Saroyo”).
As discussed above, claims 1, 2, 4-10, and 12-17 were rendered prima facie obvious by the teachings of Fahmi. The references do not teach screening agents for an effect on coronavirus cytotrophoblasts.
However, Choi teaches differentiating human pluripotent stem cells (hPSC) into cardiomyocytes and screening antiviral drugs using SARS-CoV-2 infected hPSC-derived cardiomyocytes (Graphical abstract). Saroyo teaches the effects, both advantageous and adverse of remdesivir treatment in COVID-19 positive pregnant women (Abstract).
Regarding claim 19, 22, 23 and 25, Choi teaches screening remdesivir for an effect on coronavirus infected hPSC-derviced cardiomyocytes to treat SARS-CoV 2 infection (Graphical abstract).
Regarding claim 20 and 21, Saroyo teaches no adverse events were observed in mothers, fetuses, and neonates with remdesivir treatment for COVID-19 with a reduction in duration of hospitalization (Abstract).
Fahmi, Okae, Choi and Saroyo are considered to be analogous to the claim invention because they teach methods of screening compounds against cells. Fahmi teaches ex-vivo modeling of SARS-CoV-2 infection in human placental tissue, which includes cytotrophoblasts (Summary). Okae teaches the culturing and derivation of cytotrophoblasts through both the differentiation of blastocytes and placental stem cells (Abstract). Choi teaches that remdesivir is an agent identified by screening hPSC derived cells (Graphical Abstract). Saroyo teaches that remdesivir is not harmful to the mother or the fetus (Abstract).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to screen cytotrophoblasts with antiviral agents known to be non-harmful during pregnancy such as remdesivir, as taught by Choi and Saroyo, to study coronavirus infection in cytotrophoblasts in the method taught by Fahmi and Okae because doing so would allow researchers to identify effective treatments quickly and noninvasively. One of ordinary skill in the art would have had a reasonable expectation of success in using remdesivir to screen and treat SARS-CoV-2 infected cells given that this treatment is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 3 is rejected under 35 U.S.C. 103 as being unpatentable over Fahmi and Okae as applied to claim 1, 2, 4-10, and 12-17 above, and further in view of Kim et al (J Virology, 2015, hereinafter, “Kim”).
As discussed above, claims 1, 2, 4, 5, and 8-10 were rendered prima facie obvious by the teachings of Fahmi.
The references do not teach screening agents for an effect on non-human coronavirus infected cells.
However, Kim teaches screening inhibitors to identify effective treatments for feline coronavirus infected animals (Abstract). Kim teaches that antiviral compounds can be screened in a cell culture setting or in vivo (Section: Antiviral effects of compounds in cell culture).
Regarding claim 3, Kim teaches GC376 is effective at treating feline coronavirus (Section: Results - Antiviral effects of dipeptidyl and tripeptidyl compounds on the replication of FCoV and FCV).
Fahmi, Okae, and Kim are considered to be analogous to the claim invention because they teach methods of screening compounds against cells. Fahmi teaches ex-vivo modeling of SARS-CoV-2 infection in human placental tissue, which includes cytotrophoblasts (Summary). Okae teaches the culturing and derivation of cytotrophoblasts through both the differentiation of blastocytes and placental stem cells (Abstract). Kim teaches that GC376 is an agent identified by screening cells in cell culture to treat non-human coronavirus infections(Section: Results - Antiviral effects of dipeptidyl and tripeptidyl compounds on the replication of FCoV and FCV, Antiviral effects of compounds in cell culture).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to use cytotrophoblasts, as taught by Fahmi and Okae, as a medium to screen antiviral agents in their efficacy towards non-human coronavirus as taught by Kim because doing so would allow researchers to identify effective treatments quickly and noninvasively for non-human coronaviruses. One of ordinary skill in the art would have had a reasonable expectation of success in to screen non-human coronavirus infected cells given that this treatment is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claim(s) 24 is rejected under 35 U.S.C. 103 as being unpatentable over Fahmi, Okae, Choi, and Saroyo as applied to claim 1, 2, 4, 5, 8-10, 19 - 23 and 25 above, and further in view of Kim.
As discussed above, claims 1, 2, 4, 5, 8-10, 19-23 and 25 were rendered prima facie obvious by the teachings of Fahmi, Okae, Choi, and Saroyo.
The references do not teach screening agents for an effect on non-human coronavirus infected cells.
However, as discussed above, Kim teaches screening inhibitors to identify effective treatments for feline coronavirus infected animals (Abstract). Kim teaches that antiviral compounds can be screened in a cell culture setting or in vivo (Section: Antiviral effects of compounds in cell culture).
Regarding claim 24, Kim teaches GC376 is effective at treating feline coronavirus (Section: Results - Antiviral effects of dipeptidyl and tripeptidyl compounds on the replication of FCoV and FCV).
Fahmi, Okae, Choi, Saroyo, and Kim are considered to be analogous to the claim invention because they teach methods of screening compounds against cells. Fahmi teaches ex-vivo modeling of SARS-CoV-2 infection in human placental tissue, which includes cytotrophoblasts (Summary). Okae teaches the culturing and derivation of cytotrophoblasts through both the differentiation of blastocytes and placental stem cells (Abstract). Choi teaches that remdesivir is an agent identified by screening hPSC derived cells (Graphical Abstract). Saroyo teaches that remdesivir is not harmful to the mother or the fetus (Abstract). Kim teaches that GC376 is an agent identified by screening cells in cell culture to treat non-human coronavirus infections (Section: Results - Antiviral effects of dipeptidyl and tripeptidyl compounds on the replication of FCoV and FCV, Antiviral effects of compounds in cell culture).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to use cytotrophoblasts, as taught by Fahmi and Okae, as a medium to screen cytotrophoblasts with antiviral agents known to be non-harmful during pregnancy such as remdesivir, in their efficacy towards non-human coronavirus as taught by as taught by Kim, Choi, and Saroyo,because doing so would allow researchers to identify effective treatments quickly and noninvasively for non-human coronaviruses. One of ordinary skill in the art would have had a reasonable expectation of success in to screen non-human coronavirus infected cells given that this treatment is well known, has been successfully demonstrated, and commonly used in the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant'sdisclosure:
Morotti et al (Pathogens 2021)
Yang et al (Cell Stem Cell 2020)
Zhou et al (Journal of infectious diseases 2021)
Yabe et al (PNAS 2016)
Wei et al (STAR protocols 2022)
Constantino (Front Mol Biosci 2021)
Guo et al (Front Immunol 2022)
Schwartz et al (J Dev Biol 2021)
Bukowska-Osko (Int J Mol Sci 2021)
Lu-Culligan (Cell press Med 2021)
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danyal H Alam whose telephone number is (571)272-1102. The examiner can normally be reached M - F 9am - 5pm.
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, Thomas J. Visone can be reached at 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANYAL HASSAN ALAM/ Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672
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