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 .
Detailed Action
Summary
This is the Final Office Action based on application 17/787015 response filed 04/29/2026.
Claims 1-12, 14-19 have been examined and fully considered.
Claim 13 has been cancelled.
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 1-7, 10-12, 14, & 18 are rejected under 35 U.S.C. 103 as being obvious over BUCHBERGER in EP 3367095 in view of PubChem (with way back machine date of December 18, 2014).
With respect to Claim 1, BUCHBERGER teaches of a method of unmasking endotoxin in a solution (abstract).
The solution includes a “biphasic mixture,” including a liquid phase (which contains a masked endotoxin and a protein molecule of interest) and it is suspected of containing an endotoxin and also contains an endotoxin masker, and the method comprises adding a modulator to the solution which is capable of unmasking the endotoxin (BUCHBERGER, Claim 1, Figure 1).
BUCHBERGER teaches that an aqueous (containing liquid water) composition is used to perform this (unmasking of a masked endotoxin) wherein the composition comprises a protein and an aliphatic compound. The aliphatic compound, which is 1-dodecanol here, stabilizes a potentially contaminating lipopolysaccharide molecule/LPS (also known as endotoxin) in a form that renders the LPS more susceptible to detection by conventional endotoxin test kids such as EndoLISA ® (paragraphs 0008, & 0017-0024, 0010, 0027).
BUCHBERGER teaches that the 1-dodecanol can be used alone, or instead as 1-dodecanol together with BSA. Specifically, this is done for LPS endotoxin recovery from a detergent masker, which is polysorbate 20/citrate using the modulator system of 1-dodecanol (Page 6, last paragraph).
Therefore, this reads on the claimed limitation of the solution, not having BSA, because the option is given for the solution to not have BSA, by BUCHBERGER.
BUCHBERGER further indicates that the aliphatic compound also comprises a detergent (detergents can be in liquid or solid phase) (Claim 4), which even further can include the dodecyl compound to be a detergent which is dodecyl methyl sulfoxide (Claim 5).
BUCHBERGER further teaches that unless otherwise noted all experiments taught in BUCHBERGER are performed at room temperature (paragraph 0163). (This generally means 20-25 degrees Celsius or 68-77 degrees Fahrenheit.)
In paragraph 0251, BUCHBERGER further defines "ambient temperature", a synonym for room temperature, to be 22°C, and says that the temperature is increased to this temperature for the reaction to proceed.
Instant claim 1 requires that the mixture is biphasic and that a “solid phase,” 1- dodecanol is used.1-dodecanol has the material property of being in the solid phase at room temperature. Since BUCHBERGER teaches of using 1-dodecanol at room or ambient temperature, it is in the solid- phase. Therefore, since the 1-dodecanol is a solid at room temperature and the other part of the mixture used including the protein of interest and masked endotoxin is in a liquid (BUCHBERGER, Claim 1, Figure 1), what is taught by BUCHBERGER is a “biphasic,” mixture, containing a mixture of a solid phase and liquid phase.
If this is unclear to one of ordinary skill in the art that 1 – dodecanol would be solid at room temperature, PubChem is used to remedy this.
PubChem teaches that 1-dodecanol has a melting point (where it turns from solid to liquid) of 24 degrees Celsius (Page 14, last paragraph, Page 15, first paragraph).
Therefore—the 1-dodecanol taught in BUCHBERGER wherein the temperature is raised to 22 degrees Celsius (paragraph 0163 of BUCHENBERGER), is in solid phase.
BUCHBERGER teaches that the 1-dodecanol is added as solution at room temperature to the sample to be unmasked (paragraph 0190). According to the instant application (see claim 2 and specification page 26, paragraph 2:) at temperatures below 24°C, 1-dodecanol is forming a solid phase. Therefore, this means a solid, “phase,” 1-dodecanol is added to a liquid “solution,” in REICH since the temperature is below 24 degrees. It would have been obvious to one or ordinary skill in the art before the effective filing date of the instant invention, to solubilize 1- dodecanol into a liquid solution at under 24 degrees Celsius, due to the advantage working at room temperature has for ease of use in a laboratory setting.
With respect to Claim 2, see Claim 1 rejection. BUCHBERGER teaches of a method of unmasking endotoxin in a solution (abstract),
The solution in liquid phase (which contains a masked endotoxin and a protein molecule of interest) is suspected of containing an endotoxin and also contains an endotoxin masker, and the method comprises adding a modulator to the solution which is capable of unmasking the endotoxin (BUCHBERGER, Claim 1, Figure 1).
BUCHBERGER teaches that an aqueous composition is used to perform this wherein the composition comprises a protein and an aliphatic compound. The aliphatic compound, which is 1-dodecanol here, stabilizes a potentially contaminating lipopolysaccharide molecule/LPS (also known as endotoxin) in a form that renders the LPS more susceptible to detection by conventional endotoxin test kids such as EndoLISA ® (paragraphs 0008, & 0017-0024, 0010, 0027).
BUCHBERGER further indicates that the aliphatic compound also comprises a detergent (detergents can be in liquid or solid phase) (Claim 4), which even further can include the dodecyl compound to be a detergent which is dodecyl methyl sulfoxide (Claim 5).
Notably BUCHBERGER teaches that the 1-dodecanol is added to make it a solution in liquid phase, “Unmasking of endotoxin was performed as follows: Either 100 .Math.l of a 50 mM 1-dodecanol stock solution; or 100 .Math.l of 100 mg/ml BSA and 100 .Math.l of a 50 mM 1-dodecanol stock solution; or 100 .Math.l of a 1 M CaCl.sub.2 solution, 100 ml of a 100 mg/ml BSA solution, 100 .Math.l of a 1 % SDS solution and 100 .Math.l of a 50 mM 1-dodecanol solution were added to the solution containing masked LPS. In the case of addition of combinations, the agents were added sequentially with a 2-minute vortexing step between each addition. The samples were then incubated at room temperature for 30 minutes without shaking,” (paragraph 0191).
BUCHBERGER also teaches that the 1-dodecanol can be used alone, or instead as 1-dodecanol together with BSA. Specifically, this is done for LPS endotoxin recovery from a detergent masker, which is polysorbate 20/citrate using the modulator system of 1-dodecanol (Page 6, last paragraph).
BUCHBERGER further teaches that unless otherwise noted all experiments taught in BUCHBERGER are performed at room temperature (paragraph 0163). (This generally means 20-25 degrees Celsius or 68-77 degrees Fahrenheit.)
Instant Claim 2 requires that the solution is cooled to a temperature below 24 degrees Celsius. It is noted that any mixing of components together creates a small about of heat and friction between sample components. Therefore, through broadest reasonable interpretation, “incubated at room temperature,” can read on “cooling,” to below 24 degrees Celsius (room temperature includes temperatures below 24 degrees Celsius from about 20-24 degrees Celsius). As the phase of the 1-dodecanol is a material property…the solid phase is the phase 1 dodecanol present at 24 degrees or under, this would mean that any 1-dodecanol not solubilized would be left in solid phase and the other part which is fully solubilized would be in liquid phase.
If this is unclear to one of ordinary skill in the art that 1 – dodecanol would be solid at room temperature, PubChem is used to remedy this.
PubChem teaches that 1-dodecanol has a melting point (where it turns from solid to liquid) of 24 degrees Celsius (Page 14, last paragraph, Page 15, first paragraph).
It would have been obvious to one or ordinary skill in the art before the effective filing date of the instant invention, to solubilize 1- dodecanol into a liquid solution at under 24 degrees Celsius, due to the advantage working at room temperature has for ease of use in a laboratory setting.
With respect to Claim 3, BUCHBERGER teaches of adding polyoxyethylene glycol alkylphenol ethers which are dispersants and that these are used in combination with other endotoxin maskers/ detergents like the ones involving 1 -dodecanol already taught above (paragraph 0062, 0089, & 0092).
BUCHBERGER teaches that the 1-dodecanol can be used alone, or instead as 1-dodecanol together with BSA. Specifically, this is done for LPS endotoxin recovery from a detergent masker, which is polysorbate 20/citrate using the modulator system of 1-dodecanol (Page 6, last paragraph).
Therefore, this reads on the claimed limitation of the solution, not having BSA, because the option is given for the solution to not have BSA, by BUCHBERGER.
With respect to Claim 4, BUCHBERGER teaches of adding the buffer of chaotrophic agent having ions which are Mg2+ or Ca2+ (paragraphs 0030-0032). BUCHBERGER further teaches of the agent being magnesium chloride (paragraph 0031).
BUCHBERGER teaches that the 1-dodecanol can be used alone, or instead as 1-dodecanol together with BSA. Specifically, this is done for LPS endotoxin recovery from a detergent masker, which is polysorbate 20/citrate using the modulator system of 1-dodecanol (Page 6, last paragraph).
Therefore, this reads on the claimed limitation of the solution, not having BSA, because the option is given for the solution to not have BSA, by BUCHBERGER.
With respect to Claim 5, BUCHBERGER teaches of the composition having:
The protein (which can be an antibody) present in a concentration in the range from 0.1-20 mg/ml, preferably in the range from 1-10 mg/ml, more preferably in an amount of 10 mg/ml.
The aliphatic compound is present in the concentration from 0.01 - 100 mM, preferably in a concentration from 0.1 - 10 mM. This concentration range is in particular preferred for an 1-alkanol, preferably 1-dodecanol.
The detergent is present in a concentration from 0.001 - 1.0 wt %, preferably 0.05 - 0.5 wt %, preferably from 0.02 - 0.2 wt %.
In a further preferred embodiment, the chaotopic agent is present in a concentration from 1 mM - 1 M, preferably from 25 - 200 mM, preferably from 10 mM - 100 mM (this is the agent that includes Ca 2+ or Mg2+)
In a further preferred embodiment, the divalent cation is present in a concentration from 1 - 400 mM, preferably in a concentration from 10 - 200 mM, more preferably in a concentration from 50 - 100 mM.
In a further preferred embodiment, the pH of the composition is in the range from 2-12, preferably in the range from pH 5-10 (paragraphs 0030-0041).
As the concentration of buffer/agent containing Ca 2+ or Mg 2+ are variables that can be modified, and are considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed concentration of Ca 2+ or Mg 2+ cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the concentration of Ca 2+ or Mg 2+ in the BUCHBERGER to obtain the desired balance between the concentration and the endotoxin—See “[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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
With respect to Claim 6, BUCHBERGER teaches of a method of unmasking endotoxin in a solution (abstract),
The solution in liquid phase (which contains a masked endotoxin and a protein molecule of interest) is suspected of containing an endotoxin and also contains an endotoxin masker, and the method comprises adding a modulator to the solution which is capable of unmasking the endotoxin (BUCHBERGER, Claim 1, Figure 1).
BUCHBERGER teaches that an aqueous composition is used to perform this wherein the composition comprises a protein and an aliphatic compound. The aliphatic compound, which is 1-dodecanol here, stabilizes a potentially contaminating lipopolysaccharide molecule/LPS (also known as endotoxin) in a form that renders the LPS more susceptible to detection by conventional endotoxin test kids such as EndoLISA ® (paragraphs 0008, & 0017-0024, 0010, 0027).
BUCHBERGER further indicates that the aliphatic compound also comprises a detergent (detergents can be in liquid or solid phase) (Claim 4), which even further can include the dodecyl compound to be a detergent which is dodecyl methyl sulfoxide (Claim 5).
Notably BUCHBERGER teaches that the 1-dodecanol is added to make it a solution in liquid phase, “Unmasking of endotoxin was performed as follows: Either 100 .Math.l of a 50 mM 1-dodecanol stock solution; or 100 .Math.l of 100 mg/ml BSA and 100 .Math.l of a 50 mM 1-dodecanol stock solution; or 100 .Math.l of a 1 M CaCl.sub.2 solution, 100 ml of a 100 mg/ml BSA solution, 100 .Math.l of a 1 % SDS solution and 100 .Math.l of a 50 mM 1-dodecanol solution were added to the solution containing masked LPS. In the case of addition of combinations, the agents were added sequentially with a 2-minute vortexing step between each addition. The samples were then incubated at room temperature for 30 minutes without shaking,” (paragraph 0191).
BUCHBERGER teaches that the 1-dodecanol can be used alone, or instead as 1-dodecanol together with BSA. Specifically, this is done for LPS endotoxin recovery from a detergent masker, which is polysorbate 20/citrate using the modulator system of 1-dodecanol (Page 6, last paragraph).
Therefore, this reads on the claimed limitation of the solution, not having BSA, because the option is given for the solution to not have BSA, by BUCHBERGER.
BUCHBERGER teaches of adding the buffer of chaotrophic agent having ions which are Mg2+ or Ca2+ (paragraphs 0030-0032), which can be considered to “dilution,” liquid. BUCHBERGER further teaches of the agent being magnesium chloride (paragraph 0031).
This would yield a “sample ready for endotoxin testing,” through broadest reasonable interpretation.
BUCHBERGER further teaches that unless otherwise noted all experiments taught in BUCHBERGER are performed at room temperature (paragraph 0163). (This generally means 20-25 degrees Celsius or 68-77 degrees Fahrenheit.)
Instant Claim 2 requires that the solution is cooled to a temperature below 24 degrees Celsius. It is noted that any mixing of components together creates a small about of heat and friction between sample components. Therefore, through broadest reasonable interpretation, “incubated at room temperature,” can read on “cooling,” to below 24 degrees Celsius (room temperature includes temperatures below 24 degrees Celsius from about 20-24 degrees Celsius). As the phase of the 1-dodecanol is a material property…the solid phase is the phase 1 dodecanol present at 24 degrees or under, this would mean that any 1-dodecanol not solubilized would be left in solid phase and the other part which is fully solubilized would be in liquid phase.
If this is unclear to one of ordinary skill in the art that 1 – dodecanol would be solid at room temperature, PubChem is used to remedy this.
PubChem teaches that 1-dodecanol has a melting point (where it turns from solid to liquid) of 24 degrees Celsius (Page 14, last paragraph, Page 15, first paragraph).
It would have been obvious to one or ordinary skill in the art before the effective filing date of the instant invention, to solubilize 1- dodecanol into a liquid solution at under 24 degrees Celsius, due to the advantage working at room temperature has for ease of use in a laboratory setting.
With respect to Claim 7, BUCHBERGER teaches of adding the buffer of chaotrophic agent having ions which are Mg2+ or Ca2+ (paragraphs 0030-0032). BUCHBERGER further teaches of the agent being magnesium chloride (paragraph 0031).
With respect to Claim 10, BUCHBERGER teaches of using an LAL assay to do the endotoxin testing (paragraph 0086).
With respect to Claim 11, BUCHBERGER teach of the claimed method as shown above for Claims 1-4. Since BUCHBERGER teach of the claimed method, this would yield, “wherein a greater amount of endotoxin can be detected in the sample ready for endotoxin testing than from an otherwise identical corresponding solution containing the molecule of interest and the masked endotoxin that was not subject to the method of Claim 4,” since this would be an effect of the method and reagents used- which are taught.
With respect to Claim 12, BUCHBERGER teaches of the composition having:
The protein (which can be an antibody/solution comprising the molecule of interest) present in a concentration in the range from 0.1-20 mg/ml, preferably in the range from 1-10 mg/ml, more preferably in an amount of 10 mg/ml.
The aliphatic compound is present in the concentration from 0.01 - 100 mM, preferably in a concentration from 0.1 - 10 mM. This concentration range is in particular preferred for an 1-alkanol, preferably 1-dodecanol.
The detergent is present in a concentration from 0.001 - 1.0 wt %, preferably 0.05 - 0.5 wt %, preferably from 0.02 - 0.2 wt %.
In a further preferred embodiment, the chaotopic agent is present in a concentration from 1 mM - 1 M, preferably from 25 - 200 mM, preferably from 10 mM - 100 mM (this is the agent that includes Ca 2+ or Mg2+)
In a further preferred embodiment, the divalent cation is present in a concentration from 1 - 400 mM, preferably in a concentration from 10 - 200 mM, more preferably in a concentration from 50 - 100 mM.
In a further preferred embodiment, the pH of the composition is in the range from 2-12, preferably in the range from pH 5-10 (paragraphs 0030-0041).
As the concentration and ratio to eachother of the amount of 1-dodecanol to the amount of solution containing the molecule of interest are variables that can be modified, and are considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed concentration or ratio of the amount of 1-dodecanol to the amount of solution containing the molecule of interest cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, or ratio of the amount of 1-dodecanol to the amount of solution containing the molecule of interest in the BUCHBERGER to obtain the desired balance between the concentration and the endotoxin—See “[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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
With respect to Claim 14, BUCHBERGER teaches of detecting the molecule of interest which is an antibody (paragraph 0027).
With respect to Claim 18, BUCHBERGER teaches that the aliphatic compound is present in the concentration from 0.01 - 100 mM, preferably in a concentration from 0.1 - 10 mM. This concentration range is in particular preferred for an 1-alkanol, preferably 1-dodecanol. The 1- dodecanol is 100 % 1-dodecanol. Otherwise, it would be called something else.
Claims 8-9 are rejected under 35 U.S.C. 103 as being obvious over BUCHBERGER in EP 3367095 in view of PubChem (with way back machine date of December 18, 2014) and further in view of NICHOLAS in US 20190257821.
With respect to Claims 8-9, BUCHBERGER teaches of the above and further teaches of adding the buffer of chaotrophic agent having ions which are Mg2+ or Ca2+ (paragraphs 0030-0032). BUCHBERGER further teaches of the agent being magnesium chloride (paragraph 0031), but does not teach of the agent being magnesium sulfate.
NICHOLAS is used to remedy this and teaches of a method of detection of analytes in a sample which has endotoxin lipopolysaccharides. The test sample further includes one or more potential masking agents such as surfactants, chelating agents, a divalent cation, protein, or nucleic acid and may also include a buffer (abstract).
NICHOLAS further teaches that the divalent cation can be in the form of magnesium sulfate (paragraph 0114, 0192), and that the magnesium ion can be in a concentration of greater than 1 mM (paragraph 014).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use magnesium sulfate as is done in the method of BUCHBERGER in the methods of BUCHBERGER and PubChem due to the advantage it has in affecting the accuracy of the standard LAL assay (NICHOLAS, paragraph 0112). Further NICHOLAS teaches that the divalent may be present in the test sample at any concentration, making it obvious to one of ordinary skill in the art to optimize through routine experimentation. See MPEP 2144.05. According to this guidance: “ [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.”
Claims 15- & 19 are rejected under 35 U.S.C. 103 as being obvious over BUCHBERGER in EP 3367095 in view of PubChem (with way back machine date of December 18, 2014) and further in view of WARTHOE in US 20190162718.
With respect to Claim 15, BUCHBERGER teaches of the claimed invention as shown above. BUCHBERGER does not teach of using tanezumab.
WARTHOE is used to remedy this and teaches of a method to detect the presence of therapeutic antibody drugs (abstract), which can specifically be tanezumab (paragraph 0036).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect tanezumab as is done in WARTHOE in the method of BUCHBERGER and PubChem due to the need in the art for methods and devices capable of analyzing therapeutic monoclonal antibodies and their quantities in blood samples (WARTHOE, paragraph 0024-0025).
With respect to Claim 16, BUCHBERGER teaches of the claimed invention as shown above. BUCHBERGER does not teach of using tanezumab.
WARTHOE is used to remedy this and teaches of a method to detect the presence of therapeutic antibody drugs (abstract), which can specifically be tanezumab (paragraph 0036).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect tanezumab as is done in WARTHOE in the method of BUCHBERGER and PubChem due to the need in the art for methods and devices capable of analyzing therapeutic monoclonal antibodies and their quantities in blood samples (WARTHOE, paragraph 0024-0025).
With respect to Claims 17 & 19, BUCHBERGER teaches of the composition having:
The protein (which can be an antibody/solution comprising the molecule of interest) present in a concentration in the range from 0.1-20 mg/ml which reads on the claimed concentration (paragraphs 0030-0041). BUCHBURGER does not teach of the antibody being specifically tanezumab.
WARTHOE is used to remedy this and teaches of a method to detect the presence of therapeutic antibody drugs (abstract), which can specifically be tanezumab (paragraph 0036).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect tanezumab as is done in WARTHOE in the method of BUCHBERGER and PubChem due to the need in the art for methods and devices capable of analyzing therapeutic monoclonal antibodies and their quantities in blood samples (WARTHOE, paragraph 0024-0025).
Response to Arguments
Applicant's arguments filed 04/29/2026 have been fully considered but they are not persuasive.
The prior 112 rejections are overcome due to amendments made 04/29/2026.
With respect to the prior art, applicant argues the BUCHBERGERS teaching of using 1-dodecanol, requires that “all,” of the methods in BUCHBERGER solubilizes the 1-dodecanol in EtOH, which means that the 1-dodecanol is in liquid form when used, and not solid form. The examiner disagrees that this is the case.
The examiner notes, that applicant does not cite the specific passages they are citing to which require the 1-dodecanol to always be solubilized in EtOH, but the examiner has search the reference and has found instances of this, including paragraphs 0291-0293 and table 20a. The examiner notes, however that there is no requirement in BUCHBERGER, for the composition or solution to always use EtOH.
Further, the examiner notes that what is instantly claimed is a “mixture.”
In the instant PGPUB of applicant’s instant specification this mixture of phases is described in that the solid phase can “float,” on the liquid phase, however that the mixture can be “adding liquid phase 1-dodecanol to the solution,” and then “cooling the liquid phase 1-dodecanol solution…. to a temperature below 24 degrees Celsius, such that 1-dodecanol solidifies.” (See US 20230258664, paragraph 0014 for teaching of this.) Therefore--- even applicants own specification recognizes that liquid 1-dodecanol in a solution at a temperature less than 24 degrees Celsius, will be actually a solid phase.
The examiner notes that BUCHBERGER teaches that unless otherwise noted all experiments taught in BUCHBERGER are performed at room temperature (paragraph 0163). (This generally means 20-25 degrees Celsius or 68-77 degrees Fahrenheit.)
In paragraph 0251, BUCHBERGER further defines "ambient temperature", a synonym for room temperature, to be 22°C, and says that the temperature is increased to this temperature for the reaction to proceed. At 22 degrees, recognized by applicant, 1-dodecanol is a solid phase.
Instant claim 1 requires that the mixture is biphasic and that a “solid phase,” 1- dodecanol is used. 1-dodecanol has the material property of being in the solid phase at room temperature. Since BUCHBERGER teaches of using 1-dodecanol at room or ambient temperature, it is in the solid- phase. Therefore, since the 1-dodecanol is a solid at room temperature and the other part of the mixture used including the protein of interest and masked endotoxin is in a liquid (BUCHBERGER, Claim 1, Figure 1), what is taught by BUCHBERGER is a “biphasic,” mixture, containing a mixture of a solid phase and liquid phase, and as instantly claimed. Further—there is nothing claimed, preventing the interpretation, again which is based on material properties.
Applicant further argues that the secondary reference PubChem does not remedy the deficiencies of BUCHBERGER since there is no suggestion that 1-dodecanol is solid phase, and because PubChem is specific to the properties of 1-dodecanol, and not 1-dodecanol, specifically dissolved in EtOH--- which again applicant alludes is what is taught in all use of 1-dodecanol in BUCHBERGER.
With respect to this, the examiner notes that while she recognizes that EtOH could possibly change the phase state of 1-dodecanol at a particular temperature, nothing is claimed about the claims not allowing for EtOH usage. Further- the examiner notes that in Examples 5 & 6 of BUCHBERGER, paragraphs 0191-0194, does not seem to require that EtOH is used with the 1-dodecanol. Further—while the examiner acknowledges that EtOH is sometimes used to dissolve the 1-dodecanol as taught in BUCHBERGER, there is nothing in BUCHBERGER that shows that EtOH is always required. And, even further--- there is nothing instantly claimed which prevents the usage of EtOH.
Applicant further argues that they have instantly amended to the claims to require that no BSA is used, and that BUCHBERGER teaches BSA is required and therefore the rejection fails. The examiner disagrees.
BUCHBERGER teaches that the 1-dodecanol can be used alone, or instead as 1-dodecanol together with BSA. Specifically, this is done for LPS endotoxin recovery from a detergent masker, which is polysorbate 20/citrate using the modulator system of 1-dodecanol (Page 6, last paragraph).
Therefore, this reads on the claimed limitation of the solution, not having BSA, because the option is given for the solution to not have BSA, by BUCHBERGER.
Applicant argues that BUCHBERGER teaches that BSA helps improve unmasking and therefore one would not be motivated to exclude BSA. The examiner disagrees, as BUCHBERGER does in fact teach of using without BSA (Page 6, last paragraph).
Therefore--- one does not even need a motivation to do this, as it is a direct teaching, however motivation to not use BSA would be simple in that a lab ran out of the ingredient or for simplicity or cost saving sake.
Therefore, applicant’s arguments with respect to the prior art are not convincing and all claims remain rejected.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
REICH in EP 2955518 teaches of the invention relates to methods and compositions for unmasking endotoxins in compositions so that previously present, but undetectable endotoxins are rendered detectable (abstract). The systems can use 1-dodecanol alone or 1-dodecanol with BSA (Page 4, 2nd from bottom paragraph).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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, Maris Kessel can be reached on 571-270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
Prosecution Insights