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 .
Preliminary Amendment
The preliminary amendment dated 01/30/2026 has been entered. Claims 1-34 are pending.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The earliest possible effective filing date for the instant claims is February 12, 2021 based on the filing date of the provisional application 63/200,083.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 08/07/2025, 10/29/2024, 07/13/2023 and 07/12/2023 were considered by the examiner.
Election/Restriction
Applicant’s election with traverse of Group I in the reply filed on 01/30/2026 is acknowledged.
Claims 17-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no generic or linking claim.
Claims 1--16 are under examination.
Applicant’s species election is acknowledged. Applicant elected the following
species: 2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol. For clarity regarding the interpretation of claims 2 and 3 please see Claim Interpretation section below.
The traversal filed by the Applicant is on the grounds that the present claims are unified for at least the following reasons: searching Groups I and II does not substantially increase the search burden.
Applicant’s arguments have been fully considered but are not found persuasive as such arguments do not apply when restriction is required under 35 USC 121 and 372, as in the instantly filed application. Thus, when the Office considers international applications as an International Searching Authority, as an International Preliminary Examining Authority, and during the national stage as a Designated or Elected Office under 35 U.S.C. 371, only PCT Rule 13.1 and 13.2 will be followed when considering unity of invention of claims of different categories without regard to the practice in national applications filed under 35 U.S.C. 111. The arguments do not contest the teaching of the reference(s) cited to establish a lack of unity.
The requirement is still deemed proper and is therefore made FINAL.
Claim Interpretation
The compound in claim 2, polyethylene glycol octylphenyl ether, has been interpreted as a "genus" and the compound in claim 3, 2-[4-(2,4,4- trimethylpentan-2-yl)phenoxy]ethanol, as a "species" of that broader genus based on the specification [0026]. The composition of claim 3 is interpreted as the IUPAC name for "TRITON X-100(tm)".
Since both claims 2 and 3 have a genus/species relationship and not a species/species relationship, both claims 2 and 3 are examined.
Objections
Specification and Claims
The disclosure is objected to because of the following informalities:
1. The use of the term(s), e.g., Triton X-100, which are a trade name or a mark used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, and/or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Note that ‘Triton X-100’ is merely an example and all improper uses of trademarks in the specification should be identified by applicant and properly addressed.
Appropriate correction is required.
2. Claim 2 is objected to because of the following informalities. Claim 2 “polyethylene glycol octylphenyl ether” has been interpreted to be a “genus” and the recitation should be modified as follows: “….comprises a polyethylene glycol octylphenyl ether”[emphasis added]. This modification is necessary because any “species” can fall under that broad “genus” of “polyethylene glycol octylphenyl ethers”.
3. Claims 1, 4, 6, 8-9 and 13 are objected to because of the following informalities: These claims recite “in a range of from”. This recitation is redundant. It would be preferable to either remove “of” or remove the entire “in a range of from” recitation
4. Claim 13 is objected to because of the following informalities: claim 13 recites: “the method of claim 1, further comprising the step of:(iii) storing the incubated mixture at a temperature in a range of from about -80°C to about 8°C.”. It is unclear if the “incubated mixture” of (iii) is stored AFTER the full incubation of step (ii) is complete.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
5. Claims 1-13 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method to inactivate SARS-CoV-2 (an enveloped virus) in a biological sample with a lysis reagent comprising 0.5% of the Triton X-100 (2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol) species, does not reasonably provide enablement for: (a) the method using any non-ionic surfactant, especially any other species of the polyethylene glycol octylphenyl ether genus, and (b).any other virus, in particular, does not enable the inactivation of any non-enveloped virus. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The specification does not provide sufficient information to show all the reagent compositions and conditions to be effective to treat all enveloped viruses and does not provide sufficient information as to how a non-ionic octylphenol ethoxylate surfactant detergent can be effective at inactivating non-enveloped (naked) viruses which lack the phospholipid bilayer (envelope) and are more resistant to detergents. The specification does not provide any details or examples as to the heat inactivation method for the effective inactivation of naked viruses. The instant specification fails to provide information that would allow the skilled artisan to practice the instant invention without undue experimentation. Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art, the relative skill of those in the art, and the amount of experimentation necessary. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the Invention: Claims 1-13 are drawn to a method of inactivating at least one virus present in a biological sample, the method comprising the steps of: (i) adding a sample lysis reagent composition to the biological sample to form a mixture, wherein the sample lysis reagent composition comprises a nonionic, octylphenol ethoxylate surfactant and water, and wherein the surfactant is present in the sample lysis reagent composition at an initial concentration in a range of from about 1 wt% to about 15 wt%; and (ii) incubating the mixture for a period from about 5 minutes to about 20 minutes and at a temperature sufficient to substantially inactivate the at least one virus.
Breadth of the claims: The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims. The rejected claims are extremely broad. Applicant claims any type of virus in a biological sample to be inactivated by the claimed method.
Guidance of the Specification/Working Examples: In the instant specification, applicant has demonstrated examples disclosing: an infectivity determination for sample lysis reagent composition treatment of SARS-CoV-2 culture fluid. This study was performed to determine the extent to which the 2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol species (at 0.5% concentration) has the ability to inactivate SARS-CoV-2 without destroying the ability of the viral proteins to be detected in an antigen-based detection assay (specification, example 2 and 3). In summary, the specification only exemplifies one enveloped virus of a disclosed list of non-limited virus examples. Thus, the specification fails to provide sufficient evidence in support of the broad use of the method as recited in the instant claims.
State of the Art: It is very well known in the art that naked viruses have as their outermost covering a capsid made of protein, which makes them more virulent and resistant to be neutralized with various chemical and physical factors, including any type of nonionic, octylphenol ethoxylate surfactant. -does not destroy their structural integrity since their lipid content is almost is negligible. In addition, the heat inactivation method may require different conditions (time and temperatures) based on the virus type.
Thus, the state of the art supports that finding the desire outcome for any single type of virus is a complex and labor intensive task and does not support the broad method of inactivating all viruses with a lysis reagent comprising a surfactant and with heat inactivation as claimed in the instant application.
Predictability/Unpredictability in the Art: It is noted that the pharmaceutical/biomedical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instant claimed invention is highly unpredictable since one skilled in the art would recognize that the recitation encompasses a systematic and intense effort to identify which are the viruses that would be inactivated by the method as claimed. Thus, the skilled artisan would view that inactivation of a virus in a sample encompassed by the claims is highly unpredictable.
The Quantitation of Experimentation Required: In order to practice applicants’ invention, it would be necessary for one to design and conduct an exhaustive amount of complex experiments to demonstrate that any virus can be inactivated as claimed. One would need to design and perform sample lysis composition optimization, a nonionic, octylphenol ethoxylate surfactant concentration needed for any virus, method validation and functional validation to demonstrate the membrane proteins in the envelop are still functional to still help detect the virus in detection assays. In addition, the right conditions for heat inactivation need to be tested for all viruses including the naked viruses which would be resistant to the surfactant. Therefore, in order to practice the claimed invention, the amount of experimentation required would be considered undue and burdensome.
In conclusion, Genentech, 108 F.3d at 1366 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague limitations of general ideas that may or may not be workable.” One cannot extrapolate the teaching of the specification to the enablement of the claims because the specification does not provide multiple examples or guidance for the inactivation of any type of virus in a biological sample to be enabled by the instant specification.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary.
Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Colavita (Journal of Clinical Virology. Volume 86, January 2017, Pages 27-30) in view of Darnell (Transfusion. Volume 46, October 2006 pages 1-8) and Gorbalenya (Nature Microbiology | VOL 5 536 | March 2020 | 536–544 |)
Colavita teaches the effect of Triton X-100 (Sigma-Aldrich Inc.) on the infectivity of enveloped-viruses such as West Nile virus (WNV) and Ebola virus (EBOV) at different experimental conditions (Abstract: Study design). Triton X-100 (instant claim 3) was freshly prepared as 1% stock solution (that is, the initial concentration of instant claim 1) in Modified Eagle Medium (MEM) and, for the experiments, it was further diluted in MEM to final concentrations ranging from 0.5% to 0.01% (Page 28, 3. Study design), (instant claim 8). To establish the optimal Triton X-100 concentration, WNV was exposed for 60 min to Triton X-100 concentrations ranging from 0.5% to 0.01% (instant claim 8). It is worth noticing that from a stock concentration of 1% to a final concentration of 0.01% is a 1:100 dilution. Adding 10 microliters of a stock solution to reach a final volume of 1 ml results in a 1:100 dilution (instant claim 6). It is worth noting that the concentration of a solute in a stock is not relevant to determine the solute concentration in the final solution as it is just a stock solution, which will be diluted as needed to reach the final solute concentration. So Triton X-100 can be found as an initial stock of 1%, 5%, 10% or 15%, as decided by the person preparing the stock (instant claims 1,4-5). Similarly the volume in microliters of the stock (and the dilution factor of the stock) to be added to a biological sample is not relevant. What is important for a functional method is the final concentration of Triton X-100 in the lysis solution used to inactivate the biological sample (instant claims 1, 3-7). Colavita teaches the final concentration ranging from 0.5% to 0.01% as required by instant claim 8. Colavita also teaches that recent studies showed a complete inactivation of EBOV using Triton X-100 in combination with other chemicals or with heat treatment (Page 29, second column, second paragraph) in order to inactivate clinical samples (that is biological samples), (page 28, first column and second paragraph) (instant claim 1). Last, Colavita’s data can help investigate the inactivation capacity of Triton X-100 on EBOV in more complex biological matrices, such as blood and other biological fluids (saliva, mucus, etc., are biological fluids) (Page 29, Discussion third paragraph), (instant claims 11 and 12).
Colavita does not teach the use of heat inactivation or inactivation of SARS-Cov-2.
Darnell teaches that a virus (SARS-CoV as required by instant claim 14) was diluted in PBS Solvent/detergent (S/D) solutions (20× stock) were added to each sample of virus in PBS to achieve a final concentration of nonvolatile solvent (0.3% v/v), specifically, 1% of Triton X-100 (Sigma-Aldrich Inc.). Before the addition of the S/D solution and at the time points 2, 4, 6, and 24 hours after the addition of the S/D solution, an aliquot was removed from each of the samples and diluted 100-fold (Triton X-100) in DMEM. This dilution was necessary to stop the inactivation reaction and to negate the cytotoxic effects of the S/D on the Vero cells during the titration analysis (instant claims 1, 3, 4-7 (100 dilution) and 8). Immediately after this dilution in DMEM, the aliquots were frozen at −70°C (instant claim 13), (Page 1771, Solvent/detergent treatment), Viruses were also diluted in PBS, and samples were incubated in a water bath at 56, 60, or 65°C and removed at time points up to 120 minutes (instant claims 1, 9 and 10). After heat treatment, samples were immediately frozen at −70°C. (Page 1771, Heat treatment of virus), (instant claim 13).
Darnell does not teach that the virus to be inactivated is SARS-CoV-2.
Gorbalenya teaches the identification and phylogeny of SARS-CoV-2 within the Coronaviridae (entire article). SARS-CoV-2 clusters with SARS-CoV in trees of the species
Severe acute respiratory syndrome-related coronavirus (figure 2b) and the genus Betacoronavirus (figure 2c), (instant claim 15).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Colavita with Darnell to develop a method to inactivate enveloped viruses such as West Nile virus, Ebola virus and SARS-CoV in a biological sample by disrupting the viral phospholipid envelope with a detergent such as Triton X-100 (which is known to disrupt lipids) and heat-inactivating the virus. It would have further been obvious to use the method for SARS-CoV-2 as Gorbalenya teaches that SARS-CoV and SARS-CoV-2 are closely related virus and since the method works for other non-related enveloped virus, there is no reason to expect the method would not work for SARS-CoV-2. One of ordinary skill would have been motivated to do so because Triton X-100 and heat inactivation are known to inactivate enveloped viruses as taught by both Colavita and Darnell, including SAR-CoV-2 as taught by Gorbalenya. It would have further been obvious that the Triton X-100 concentrations in a stock and final solution, or the volume of lysis solution added to the biological sample, or temperature and time use for heat-inactivating the virus or the storage temperature to use are clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. It would have been obvious to optimize for the best surfactant and to substitute one species of polyethylene glycol octylphenyl ether for another species including 2-[4-(2,4,4- trimethylpentan-2-yl)phenoxy]ethanol. because as long as the species belongs to the same genus, they will have the same function. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." (Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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 2. The use of a detergent (a species of species of polyethylene glycol octylphenyl ether, including 2-[4-(2,4,4- trimethylpentan-2-yl)phenoxy]ethanol) and/or heat inactivation are taught in the prior art for the same purpose: inactivating the virus. Therefore, it is obvious to combine them in the same method to achieve that purpose. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
There would be a reasonable expectation of success because the use of detergent and heat inactivation is well stablished in the art and routinely practiced in many laboratories in the world.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
7. Claims 1-13 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Colavita in view of Darnell and Shih (US 2021/0199652 A1. Priority date Dec 31, 2019).
Colavita and Darnell teachings have been discussed above and applied herein.
Colavita and Darnell do not teach the method wherein the virus is Influenza virus.
Shih teaches test kits for simultaneously detecting a plurality of analytes. The test kit includes a lysis solution and a test strip. The lysis solution includes a salt, a surfactant, a stabilizer, and a buffer solution (abstract). The surfactant comprises a Triton related surfactant (claim 5), (instant claim 1). The lysis solution isolates an antigen of a respiratory virus (which reads on inactivating the virus to release the antigens) [0009] and the respiratory viruses include adenovirus, influenza A (Flu A) virus, influenza B (Flu B) virus, influenza C (Flu C) virus, respiratory syncytial virus (RSV), rhinovirus (RhV), or coronavirus (CoV) [0010] as required by instant claim 16.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Colavita with Darnell to develop a method to inactivate enveloped viruses such as West Nile virus, Ebola virus and SARS-CoV in a biological sample by disrupting the viral phospholipid envelope with a surfactant and heat-inactivating the virus. It would have further been obvious to use the method for Influenza (an enveloped virus) as Shih teaches that Influenza can be inactivated by a lysis solution containing a Triton-related detergent. Since both the Triton related surfactant and Triton X-100 (which are species of the same polyethylene glycol octylphenyl ether genus) are related are surfactants capable of inactivating a wide range of viruses including respiratory viruses such as Coronaviruses, it would have been obvious to use the method taught by Colavita and Darnell to inactivate Influenza. One of ordinary skill would have been motivated to do so because surfactants such as Triton X-100 or Triton-related surfactants, and heat inactivation are known to inactivate a wide range of enveloped viruses as taught by both Colavita and Darnell. There would be a reasonable expectation of success because the use of detergent and heat inactivation is well stablished in the art and routinely practiced in many laboratories in the world.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
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/IMMA BARRERA/
Examiner, Art Unit 1671
/RACHEL B GILL/Primary Examiner, Art Unit 1671
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