DETAILED CORRESPONDENCE
Application Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Support for the amendments are within the instant application specification.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/2/2025 has been entered.
Applicant’s amendment to the claims filed on 9/2/2025 in response to the Final Rejection mailed on 6/2/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 1-13, 15-21 are pending.
Claim 21 is newly added.
Claim 14 is cancelled.
Applicant’s remarks filed on 9/2/2025 in response to the Final Rejection mailed on 6/2/2025 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Withdrawn Rejections
The rejection of claims 12-13, 15 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated to Chowdhury et al. (2015, Avicenna Journal of Clinical Microbiology and Infection, 2(4): e31990, 24-29, cited on PTO-892 filed 5/21/2024) is withdrawn in view of Applicant’s amendment of claim 1 to recite ‘lipopolysaccharide (LPS) is extracted without using organic solvent.’
Maintained 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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The rejection of claims 12-13, 15, 21 under 35 U.S.C. 101 is maintained for the reasons of record and the reasons set forth below because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is a naturally occurring microorganism. The rejection has been modified in view of Applicant’s amendment of claim 12 to recite ‘5,000 to 20,000’ and newly added claim 21.
Step 1: Is the claim to a process, machine, manufacture or composition of matter?
Yes, the claim is drawn to a composition of matter, which is one of the four statutory categories.
Step 2, Prong One: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Yes, the claim is directed to a natural phenomenon (product of nature). Said natural phenomenon is a naturally occurring component of gram negative bacteria, lipopolysaccharide.
Claims 12-13, 15, 21 are directed towards a lipopolysaccharide that is produced by the production method according to Claim 1, wherein the lipopolysaccharide is of a high purity, high content and low molecular weight lipopolysaccharide, and wherein the lipopolysaccharide is configured to activate an immune response in a subject in which the lipopolysaccharide is provided, wherein the low molecular weight is a molecular weight as measured by an SDS-PAGE method of 5,000 to 20,000 and wherein the lipopolysaccharide also contains a high molecular weight lipopolysaccharide with a molecular weight as measured by the SDS-PAGE method of more than 20,000 but not more than 100,000, wherein the content of the low molecular weight lipopolysaccharide with respect to a total amount of the low molecular weight lipopolysaccharide and the high molecular weight lipopolysaccharide is not less than 80%, and wherein the purity of the lipopolysaccharide is not less than 70 weight %.
Step 2, Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application?
Claim 12 includes additional elements of the lipopolysaccharide being of a high purity, high content and low molecular weight lipopolysaccharide, and wherein the lipopolysaccharide is configured to activate an immune response in a subject in which the lipopolysaccharide is provided, wherein the low molecular weight is a molecular weight as measured by an SDS-PAGE method of 5,000 to 20,000 and wherein the lipopolysaccharide also contains a high molecular weight lipopolysaccharide with a molecular weight as measured by the SDS-PAGE method of more than 20,000 but not more than 100,000, wherein the content of the low molecular weight lipopolysaccharide with respect to a total amount of the low molecular weight lipopolysaccharide and the high molecular weight lipopolysaccharide is not less than 80%, and wherein the purity of the lipopolysaccharide is not less than 70 weight %. Said limitations are naturally occurring properties of the LPS since it does not include any modifications of said LPS.
Claim 13 recites ‘is obtained from the gram-negative bacterium, wherein the gram-negative bacterium is at least one selected from the group consisting of a genus Escherichia, Salmonella, Pantoea, Acetobacter, Zymomonas, Xanthomonas, Enterobacter, Roseomonas, and Rhodobactor.’ As such, said LPS is naturally occurring without any significant modifications. Said characteristics are not sufficient to integrate into a practical application (MPEP 2106.05(f)-(g)).
Claim 15 includes additional elements of wherein a value (E/L ratio) obtained by dividing a lipopolysaccharide quantitative value (E) determined by an ELISA method by a lipopolysaccharide quantitative value (L) determined by a Limulus test (endpoint chromogenic method) is not more than 1.0. Such a limitation is native to the LPS. Therefore, it does not integrate the judicial exception into a practical application for the same reasons discussed above.
Claim 21 includes additional elements of wherein the low molecular weight is a molecular weight as measured by an SDS-PAGE method of 7,000 to 17,000, wherein the lipopolysaccharide also contains a high molecular weight lipopolysaccharide with a molecular weight as measured by the SDS-PAGE method of more than 25,000 but not more than 60,000, wherein the content of the low molecular weight lipopolysaccharide with respect to a total amount of the low molecular weight lipopolysaccharide and the high molecular weight lipopolysaccharide is not less than 80%. Said limitations are naturally occurring properties of the LPS since it does not include any modifications of said LPS.
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
No. The judicial exception is recited without additional limitations amounting to significantly more than the exception. All of the signified additional elements to the judicial exception are considered to be native to the LPS which the judicial exception is to be performed as noted in Step 2A, Prong 2, and, therefore, do not amount to significantly more than the judicial exception that is claimed.
The instant Specification established that LPS in the instant Application is a naturally occurring product derived from the gram negative bacteria. Therefore it is understood that the extracted and purified LPS in this invention is identical to the naturally occurring LPS which is a product of nature. Thus, claims 12-13, 15, 21 encompass patent ineligible subject matter.
Consequently, it is understood that a LPS is necessarily a product of nature that has undergone purification to remove other chemical entities. In conclusion, a LPS does not correspond to a judicial exception of a product of nature.
As the instant claims recite judicial exceptions that are not integrated into practical application, and no elements that amount to significantly more than the judicial exception as recited, the claims were found not to be drawn to eligible subject matter under 35 U.S.C. 101.
RESPONSE TO REMARKS: Beginning on p. 1 of Applicant’s remarks, Applicants in summary contend that the differences in the E/L ratio of IP-PAI of the invention (0.71 to 0.72) versus naturally occurring LPS (1.64) provides explicit data showing the characteristics of the claimed LPS are not found in the IP-PAl standard thereby the claims clearly include patentable subject matter because the claims are not directed to a product of nature or natural phenomenon.
This argument is found to be not persuasive in view of the rejection set forth. Examiner contends that although Applicant has discovered that the LPS purified in the absence of an organic solvent has a high yield of high and low molecular weight LPS versus traditional extraction, this discovery does not, by itself, render LPS produced in the absence of an organic solvent patent eligible. Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. __, 133 S. Ct. 2107, 2117 (2013) (“Myriad”). Instead, the claimed purified LPS is analyzed to determine if purifying the LPS in the absence of an organic solvent results in a higher yield than utilizing traditional methods of purifying LPS. Based on the limited background information, there is no indication that purifying LPS in the absence of an organic solvent has any characteristics (structural, functional, or otherwise) that are different from the naturally occurring LPS. The claim therefore encompasses LPS that is structurally and functionally identical to naturally occurring LPS. Examiner contends that difference in E/L ratio of IP-PAI of the low molecular weight LPS does not markedly change the LPS of the invention as said LPS is simply purified in greater yields. As such, Examiner contends that Applicant has not demonstrated any markedly different characteristics of the invention vs the naturally occurring LPS. Examiner contends that simply purifying the LPS, especially in the absence of an organic solvent, does not markedly change it from its naturally occurring self. Examiner contends that purifying the LPS and discovering that one is able to obtain a higher yield of product does not markedly change the naturally occurring LPS from the purified LPS extracted without using organic solvent. Because there is no difference between the claimed and naturally occurring LPS, the claimed LPS does not have markedly different characteristics from what occurs in nature, and thus is a “product of nature” exception.
Maintained 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 rejection of claims 1-10, 12-13, 15-21 under 35 U.S.C. 103 as being unpatentable over Chowdhury et al. (2015, Avicenna Journal of Clinical Microbiology and Infection, 2(4): e31990, 24-29, cited on PTO-892 filed 5/21/2024) {herein Chowdhury} in view of Agilent Technologies (2017, cited on PTO-892 filed 5/21/2024) {herein Agilent} as evidenced by Lumen et al (2025, Lipids, Biology for Majors, cited on PTO-892 dated 6/2/2025) {herein Lumen} and Varanets et al (2017, Microbiology, cited on PTO-892 dated 6/2/2025) {herein Varanets}. The rejection is maintained for the reasons of record and the reasons set forth. The rejection has been modified to add claims 12-13, 15, 21; in view of Applicant’s recitation of ‘lipopolysaccharide (LPS) is extracted without using organic solvent’ in claim 1 of the instant application and to add evidentiary reference Varanets et al (2017, Microbiology, cited on PTO-892 dated 6/2/2025) {herein Varanets}.
As amended, claims 1-10, 16-20 are drawn to A lipopolysaccharide production method in which a lipopolysaccharide (LPS) is extracted without using organic solvent and purified from gram-negative bacterium, the lipopolysaccharide production method comprising: a first step of performing extraction from the gram-negative bacterium using hot water to obtain an extract liquid that contains the lipopolysaccharide, wherein performing extraction does not use organic solvent; and a second step of purifying the extract liquid or a solution containing the LPS in the extract liquid by using reverse-phase liquid chromatography to obtain the lipopolysaccharide, wherein a reverse-phase column used in the reverse-phase liquid chromatography has a packing material constituted of a material having a functional group of 1 to 8 carbons.
As amended, claims 12-13, 15, 21 are drawn to a lipopolysaccharide that is produced by the production method according to Claim 1, wherein the lipopolysaccharide is of a high purity, high content and low molecular weight lipopolysaccharide, and wherein the lipopolysaccharide is configured to activate an immune response in a subject in which the lipopolysaccharide is provided, wherein the low molecular weight is a molecular weight as measured by an SDS-PAGE method of 5,000 to 20,000 and wherein the lipopolysaccharide also contains a high molecular weight lipopolysaccharide with a molecular weight as measured by the SDS-PAGE method of more than 20,000 but not more than 100,000, wherein the content of the low molecular weight lipopolysaccharide with respect to a total amount of the low molecular weight lipopolysaccharide and the high molecular weight lipopolysaccharide is not less than 80%, and wherein the purity of the lipopolysaccharide is not less than 70 weight %.
With respect to claims 1, 10, Chowdhury teaches a method of purification, extraction, and visualization of LPS from Escherichia coli (E.coli) (abstract; page 25, column 2, para 3). The first step of the LPS extraction began with 1× pelleted bacteria being resuspended in 200 µL of SDS buffer (page 25, column 2, para 3). Examiner is interpreting the SDS buffer as an inorganic solvent. Then the suspended bacteria were boiled in a water bath (Shel Lab) for 15 minutes (page 25, column 2, para 3). Examiner is interpreting said step to the be the first step in LPS extraction and purification. Furthermore, Examiner is interpreting said step to be method in which a lipopolysaccharide (LPS) is extracted without using organic solvent.
With respect to claims 6-9, 19-20, Chowdhury teaches a method wherein the bacteria are subjected to boiling in a water bath (pages 25, column 2, para 3). Examiner is interpreting the temperature of boiling water to be 100C. Chowdhury also teaches incubation at 59C and 65C during the course of the extraction procedure (page 25, column 2, para 3).
With respect to claims 12-13, 21, Chowdhury teaches LPS from Escherichia coli (page 25, column 2, para 3). The evidentiary reference of Varanets is cited to demonstrate that the structural composition of LPS within species of the family Enterobacteriaceae are typical among bacterial species of that family (page 58, column 2, para 6). As such, Examiner is interpreting the LPS of the claimed Enterobacter to have the same structural characteristics as that of the E. coli taught by Chowdhury since it is known by those of ordinary skill in the art that E.coli is a member of the Enterobacteriaceae family. Examiner is interpreting the high-molecular weight LPS of claims 12 and 21 to be in lanes 1-4, 6-10, where the blue arrow below is indicating below. Examiner is interpreting the low molecular weight LPS of claims 12 and 21 to be where the green arrow is indicated below.
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Chowdhury further teaches that the extracted and purified LPS, as from the results of the SDS-PAGE, showed a low molecular weight LPS (green arrow), of which Examiner is interpreting to be the same as recited in claims 12 and 21 since the indicated purified LPS is greater than 5,000 Da (claim 12) and 7,000 Da (claim 21), but less than 20,000 Da (claim 12) and 17,000 Da (claim 21). In addition, Chowdhury teaches a high molecular weight LPS (blue arrow), of which Examiner is interpreting to be the same as recited claims 12 and 21 since the indicated purified LPS (blue arrow) is greater than 20,000 Da (claim 12) and 25,000 Da (claim 21), but less than 100,000 Da (claim 12) and 60,000 Da (claim 21). Examiner is interpreting the total for the low molecular weight LPS and the high molecular weight LPS accounted for more than 80% of the LPS, which is evident by the teaching of Chowdhury which recites ‘the staining revealed dark trail-like bands of purified LPS’ (page 26, figure 1 legend). Examiner is interpreting the trail-like bands to cover over 80% of the gel. As such, said characteristics of the LPS taught by Chowdhury are the same characteristics of the LPS claimed by Applicant. Chowdhury teaches the LPS extraction and purification comprising the first step of extraction in which the suspended E.coli cells are boiled in a water bath for 15 minutes followed by Coomassie blue staining and silver staining leading to successful extraction and purification of LPS from E.coli (Figures 1 and 2, page 26). This shows that the content of the low molecular weight and the high molecular weight LPSs are more than 80%.
Since the Office does not have the facilities for examining and comparing applicants’ LPS with the LPS of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the lipopolysaccharide is configured to activate an immune response in a subject in which the lipopolysaccharide is provided). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594. However, given that Chowdhury teaches the properties of the LPS, absent evidence otherwise, it is the Examiner’s position that the lipopolysaccharide taught by Chowdhury would necessarily be configured to activate an immune response in a subject.
With respect to claim 15, Examiner takes the position that the LPS taught by Chowdhury also inherently has the same characteristics as claimed in claim 15. Since the office does not have the facilities for examining and comparing applicants’ LPS with the LPS of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the LPS of the prior art does not possess the same material structural and functional characteristics of the claimed LPS). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594. ‘ However, given that Chowdhury teaches LPS from Escherichia coli, a member of the Enterobacteriaceae family of which Enterobacter belongs (page 25, column 1, para 1), absent evidence otherwise, it is the Examiner’s position that Chowdhury would necessarily have LPS with a value (E/L ratio) obtained by dividing a lipopolysaccharide quantitative value (E) determined by an ELISA method by a lipopolysaccharide quantitative value (L) determined by a Limulus test (endpoint chromogenic method) is not more than 1.0, as the evidentiary reference of Varanets is cited to demonstrate that the structural composition of LPS within species of the family Enterobacteriaceae are typical among bacterial species of that family (page 58, column 2, para 6). As such, Examiner is interpreting the LPS of the claimed Enterobacter to have the same structural characteristics as that of the E. coli taught by Chowdhury since it is known by those of ordinary skill in the art that E.coli is a member of the Enterobacteriaceae family.
However, Chowdhury does not teach a second step of purifying the extract liquid or a solution containing the LPS in the extract liquid by using reverse-phase liquid chromatography to obtain the lipopolysaccharide, wherein a reverse-phase column used in the reverse-phase liquid chromatography has a packing material constituted of a material having a functional group of 1 to 8 carbons (claim 1). The lipopolysaccharide production method according to Claim 1, wherein the packing material is constituted of a material having a functional group of 2 to 6 carbons (claim 2). The lipopolysaccharide production method according to Claim 1, wherein the packing material is constituted of a material having a functional group of 2 to 4 carbons (claim 3). The lipopolysaccharide production method according to Claim 1, wherein the packing material is constituted of a material having a functional group of 4 carbons (claim 4). The lipopolysaccharide production method according to Claim 1, wherein the functional group is an alkyl group (claim 5). The lipopolysaccharide production method according to Claim 2, wherein the packing material is constituted of a material having a functional group of 2 to 4 carbons (claim 16). The lipopolysaccharide production method according to Claim 2, wherein the packing material is constituted of a material having a functional group of 4 carbons (claim 17). The lipopolysaccharide production method according to Claim 2, wherein the functional group is an alkyl group (claim 18).
With respect to claims 1-4, 16-18, Agilent teaches a method wherein reverse phase chromatography is used for the purification of macro molecules with nonpolar hydrocarbon chains (page 19). Evidentiary reference of Lumen is cited to demonstrate that lipids are hydrocarbons that are mostly nonpolar hydrophobic molecules (page 2, para 1). As such, it would be obvious to one of ordinary skill that reverse-phase chromatography could be used for the purification of LPS as LPS contains a hydrophobic lipid A region with nonpolar hydrocarbon chains. Furthermore, the silica gels in the column stationary phase are the packing material with the hydrocarbon chains between 1 and 18 carbon atoms as the functional group because they function to separate the mixture (page 19). Examiner is interpreting 1 to 8 carbons claimed by Applicant to encompass 1 to 18 carbons taught by Agilent. A prima facie case of obviousness exists where the claimed ranges and prior art ranges overlap, such as in the instant rejection. MPEP § 2144.05.
With respect to claims 5, 18, Agilent teaches a method wherein the packing material has an alkyl functional group (page 27).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to combine the teachings of Chowdhury and Agilent because Agilent teaches a method wherein reverse phase chromatography is used for the purification of macromolecules (page 47, para 2). While Chowdhury teaches a method wherein the first step in the purification, extraction, and visualization of LPS from E. coli consists of SDS treatment and boiling the sample in hot water (abstract; page 25, column 2, para 3).
One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability, and would be motivated to combine the teachings of Chowdhury and Agilent because Agilent provides the motivation to use reverse phase chromatography for the purification of LPS since Agilent established that the packed column in reverse liquid chromatography with the alkyl functional group is successful for the purification of macro molecules with nonpolar hydrocarbon chains (page 19). Since LPS contains nonpolar hydrocarbons, it would be obvious to one of ordinary skill in that art that LPS can be purified by reverse-phase chromatography. In addition, one of ordinary skill in the art would utilize reverse-phase chromatography for LPS purification because said process is able to separate products based on their hydrophobicity (Agilent: page 19), thereby allowing for separation and quantification based on the relative hydrophobicity of the LPS. Furthermore, one of ordinary skill in the art would be motivated to only perform the first step of LPS purification taught by Chowdhury of not adding an organic solvent as the addition of an organic solvent would contaminate the LPS, thereby requiring an additional steps of purification before being utilized for experimentation. Furthermore, one of ordinary skill in the art would be motivated to utilize Chowdhury’s first step of LPS purification and the second step taught by Agilent as doing so would reduce the number of steps needed for purification, thereby resulting in a more time-efficient method of purification and a reduction in costs as said method would not require an organic solvent. One of skill in the art would have a reasonable expectation of success to make and use the claimed lipopolysaccharide production method because Chowdhury provides the basic method for producing LPS from gram negative bacteria and its uses and methods of making it. Agilent provides the steps of reverse-phase liquid chromatography for the purification of macromolecules with nonpolar hydrocarbons for optimized resolution.
One of ordinary skill in the art would be motivated to combine the teachings of Chowdhury and Agilent because doing so would produce purified LPS with higher concentration and less artifacts (contaminants). Furthermore, the extraction method taught by Chowdhury is routinely done within the art, therefore the supplies for the method are widely available. As such, one of skill in the art would be motivated to utilize said methods for the purification of LPS. Therefore there would be a reasonable expectation of success to arrive at the above invention. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
RESPONSE TO REMARKS: Beginning on p. 9 of Applicant’s remarks, in summary, Applicant contends that the rejection appears to concede that Chowdhury uses an organic solvent in the extraction step, since the explanation provided on page 17 of the Office Action suggests that only some steps in the extraction don't use organic solvent.
This argument is found to be not persuasive in view of the modified rejection set forth. Examiner contends that one of ordinary skill in the art would be motivated to utilize Chowdhury’s first step of LPS purification and the second step taught by Agilent as doing so would reduce the number of steps needed for purification, thereby resulting in a more time-efficient method of purification and a reduction in costs as said method would not require an organic solvent. Furthermore, one of ordinary skill in the art would be motivated to only perform the first step of LPS purification taught by Chowdhury of not adding an organic solvent as the addition of an organic solvent could contaminate the LPS, thereby requiring an additional steps of purification before being utilized for experimentation. In addition, Examiner contends that claim 1 recites ‘a first step of performing extraction from the gram-negative bacterium using hot water to obtain an extract liquid that contains the lipopolysaccharide’ which is explicitly taught by Chowdhury with the recitation’ the first step of the LPS extraction began with 1× pelleted bacteria being resuspended in 200 µL of SDS buffer (page 25, column 2, para 3).’
Applicant contends that Chowdhury explicitly states, at least in the description of Fig. 2, "Lipopolysaccharide from ten E. coli strains from urine samples of patients with UTI was purified by modified hot-aqueous phenol extraction...." (Chowdhury, p. 26, col. 2, emphasis added).
This argument is found to be not persuasive in view of the modified rejection set forth. Examiner contends that since the Office does not have the facilities for examining and comparing applicants’ LPS with the LPS of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the lipopolysaccharide is configured to activate an immune response in a subject in which the lipopolysaccharide is provided). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594. However, given that Chowdhury teaches the properties of the LPS, absent evidence otherwise, it is the Examiner’s position that the lipopolysaccharide taught by Chowdhury would necessarily be configured to activate an immune response in a subject.
The rejection of claim 11 under 35 U.S.C. 103 as being unpatentable over Chowdhury et al. (2015, Avicenna Journal of Clinical Microbiology and Infection, 2(4): e31990, 24-29, cited on PTO-892 filed 5/21/2024) {herein Chowdhury} in view of Agilent Technologies (2017, cited on PTO-892 filed 5/21/2024) {herein Agilent} as applied to claims 1-10, 12-13, 15-21 and in further view of Inagawa (JP 2018035084A published on March 8, 2018 and filed on August 30, 2016, cited on PTO-892 filed 5/21/2024) {herein Inagawa} as evidenced by Lumen et al (2025, Lipids, Biology for Majors, cited on PTO-892 dated 6/2/2025) {herein Lumen} is maintained for the reasons of record and the reasons set forth. The rejection has been modified to add claims 12-13, 15, 21; in view of Applicant’s recitation of ‘lipopolysaccharide (LPS) is extracted without using organic solvent’ in claim 1 of the instant application and to add evidentiary reference Varanets et al (2017, Microbiology, cited on PTO-892 dated 6/2/2025) {herein Varanets}.
Previously presented claim 11 is drawn to the lipopolysaccharide production method according to Claim 1, wherein the gram-negative bacterium belongs to the genus Pantoea.
The teachings of Chowdhury and Agilent as applied to claims 1-10, 16-20 are set forth in the 103 rejection above.
However, Chowdhury and Agilent do not teach the lipopolysaccharide production method according to Claim 1, wherein the gram-negative bacterium belongs to the genus Pantoea (claim 11).
With respect to claim 11, Inagawa teaches a method of LPS extraction and purification from Pantoea agglomerans (para 0010).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to combine the teachings of Chowdhury and Agilent in view of Inagawa because Inagawa teaches a method of LPS extraction and purification from Pantoea agglomerans by suspending said cells in distilled water (para 0010). Agilent teaches a method wherein reverse phase chromatography is used for the purification of proteins (page 47, para 2). While Chowdhury teaches a method wherein the first step in the purification, extraction, and visualization of LPS from E. coli consists of SDS treatment and boiling the sample in hot water (abstract; page 25, column 2, para 3).
One of ordinary skill in the art would have had a reasonable expectation of success, a reasonable level of predictability, and would be motivated to combine the teachings of Chowdhury, Agilent and Inagawa because Inagawa provides the motivation to use Pantoea agglomerans for extraction of LPS since said microorganism produces a low molecular weight lipopolysaccharide (LMM-LPS) that exhibits extremely high safety and high biological activity (para 0001). As such, one of ordinary skill in the art would be motivated to utilize said microorganism for the purification of LPS since it would be effective at producing highly pure and biologically active LPS during the extraction and purification processes. One would be motivated to utilize the microorganism taught by Inagawa because the purified LPS could be utilized for experimentation due to its biologically active LPS and high purity. Therefore there would be a reasonable expectation of success to arrive at the above invention. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
RESPONSE TO REMARKS: Beginning on p. 10 of Applicant’s remarks, Applicant in summary
contends that Inagawa disclosed using organic solvent in the extraction step.
This argument is found to be not persuasive in view of the rejection set forth above. Examiner contends that Inagawa cures the deficiencies of Chowdhury and Agilent by teaching a method of LPS extraction and purification from Pantoea agglomerans by suspending said cells in distilled water (para 0010). The first step of said method taught by Inagawa does not involve the use of an organic solvent, as it only involves the use of distilled water. As such, Examiner contends that Chowdhury in view of Inagawa teaches the limitations of claim 11 of ‘wherein the gram-negative bacterium belongs to the genus Pantoea.’ Additionally, Inagawa teaches the purification of Pantoea wherein the first step of purification is the addition of distilled water (para 0010). Examiner contends that one of ordinary skill in the art would be motivated to not use an organic solvent for the purification of LPS as doing so could create artifacts that could have a negative effect on the experiment. Additionally, Examiner contends that claim 1 recites ‘a first step of performing extraction from the gram-negative bacterium using hot water to obtain an extract liquid that contains the lipopolysaccharide’ which is explicitly taught by Chowdhury and Inagawa in the 103 rejections. As such, said teaching reads, in-part, on the independent claim 1, of a first step of performing extraction from the gram-negative bacterium using water to obtain an extract liquid that contains the lipopolysaccharide.
Conclusion
Status of the claims:
Claims 1-13, 15-21 are pending.
Claim 14 is cancelled.
Claims 1-13, 15-21 are rejected.
No claims are in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERICA NICOLE JONES-FOSTER whose telephone number is (571)270-0360. The examiner can normally be reached mf 7:30a - 4:30p.
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/ERICA NICOLE JONES-FOSTER/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656