DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Applicant's submission filed on 23 October 2025 has been entered, and the arguments presented therein have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 101 – Subject Matter Eligibility
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.
Claim 28 is rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of an abstract idea without significantly more. The examiner notes the following guidelines for analysis under 35 U.S.C. 101.
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As to step 1, the claim is drawn to a process (i.e. method).
Step 2A is further broken down into two prongs, as follows:
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As to step 2A prong 1, claim 28 is understood to be drawn to an abstract idea because characterizing a membrane protein is an abstract idea. This is because the end result of this characterization occurs in the mind of the person conducting the characterization step.
As to step 2A, prong 2, the steps of providing the lipid nanodisc and contacting the nanodisc with the membrane protein is understood to be insignificant extra-solution activity because it is mere data gathering in preparation for the step of characterization. MPEP 2106.04(d)(I) indicates that “[a]dding insignificant extra-solution activity to the judicial exception, as discussed in MPEP § 2106.05(g)” does not integrate a judicial exception into a practical application. Looking toward MPEP 2106.05(g), this section of the MPEP indicates that performing clinical tests and determining the level of a biomarker in blood is understood to be mere data gathering that is insignificant extra-solution activity.
As to step 2B, it is the examiner’s understanding that characterizing a chemical species is well-understood, routine and conventional. Even if, purely en arguendo, the use of the recited lipid nanodisc is not routine and conventional, this does not affect the overall conclusion of a lack of patent eligibility because the recited lipid nanodisc is being used for the step of data gathering in preparation for the characterization step, and the step of data gathering is insignificant extra-solution activity.
This rejection was not made previously in prosecution because the examiner made an error by not rejecting claim 28 on this ground. This error has been corrected in this office action. As such, this office action has been made NON-FINAL.
The examiner suggests the following claim amendment to overcome these issues; see the next page for the proposed amendment set forth on the next page.
Claim 28 (Proposed Amendment): A method [[ ]] comprising:
contacting the lipid nanodisc of [[ ]] claim 1 with a membrane protein to form a membrane protein-nanodisc comprising the membrane protein spanning across the lipid bilayer from the first hydrophilic face to the second hydrophilic face; [[
]] wherein the membrane protein that has been contacted with the lipid nanodisc [[ ]] is capable of being characterized by performing at least one characterization method selected from the group consisting of solution nuclear magnetic resonance (NMR), solid state NMR, circular dichroism, electron paramagnetic resonance (EPR), Fourier transform infrared spectroscopy (FTIR), resonance Raman spectroscopy, ultraviolet-visible spectroscopy (UV/vis), cryo-electron microscopy (cryo-EM), surface plasmon Raman spectroscopy, sum frequency generation (SFG), fluorescence, small angle x-ray scattering (SAXS), scanning electron microscopy (SEM), atomic force microscopy (AFM), and an enzymatic assay.
The examiner clarifies that the above-proposed amendment is intended only to overcome the patent eligibility issue and does not, in itself, overcome any other ground of rejection. The examiner also clarifies that the proposed amendment is adequately supported as of the instant specification on page 4, paragraph 0023.
Claim Rejections - 35 USC § 112(b) – Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4, 7-9, 11, 13-14, 16-18, 20, 22, 25-26, 28, and 33 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 has been amended to recite that 5% to 15% of the hydroxyl groups of the polysaccharide are modified with a hydrophobic group. This renders the claims to be indefinite because it is unclear how the hydrophobic group further limits the polysaccharide. The examiner presents the following rationale in support of this position.
As an initial matter, the examiner notes that the term “hydroxyl group” is used in organic chemistry to refer to a chemical with the formula:
R1-OH
wherein H is hydrogen, O is oxygen, and R is part of an organic molecule comprising carbon and hydrogen, and wherein the bonds between R and O as well as between O and H are covalent. The skilled artisan would also have understood that a compound with the formula
R1-O-R2
is not a hydroxyl group because it does not have an oxygen bound to a hydrogen. In contrast, R1-O-R2 is an ether group if R2 is an alkyl group or an ester group is R2 is an acyl group.
As such, it is unclear whether claim 1 is reciting that:
that 5% to 15% of the R1 groups are hydrophobic (e.g. such as stearyl alcohol) and that the remaining R1 groups are not hydrophobic; or
That 5% to 15% of the original hydroxyl groups in the polysaccharide have been modified to be R1-O-R2 and are therefore no longer hydroxyl groups, whereas the remaining hydroxyl groups from the polysaccharide still remain as hydroxyl groups.
For the purposes of examination under prior art, the examiner will proceed with examination with the understanding that interpretation “B” is the appropriate claim interpretation because this appears to be the interpretation intended by applicant. This determination is made in view of the instant specification on pages 8-9, paragraph 0064.
In order to overcome this rejection to amend the claims to be in concert with interpretation “B”, applicant must amend the claim to clarify that the 5% to 15% of the hydroxyl groups present in the original polymer that have been modified are no longer hydroxyl groups. This statement should not be construed as an assurance that such an amendment would not be new matter. With that being said, the examiner takes the position that the idea that an ester or ether formed by hydrophobic modification of a hydroxyl group is no longer a hydroxyl group is obviously incorrect. As such, correction of this issue may potentially amount to correction of an obvious error as per MPEP 2163.07(II).
Claim Interpretation
Claim 3 recites various polysaccharides and derivatives thereof. However, the examiner notes that claim 1 already recites that the polysaccharides are modified with a hydrophobic group. For the purposes of examination under prior art, the derivatives of polysaccharides recited by claim 3 are understood to refer to polysaccharides that are both hydrophobically modified, as in claim 1, and otherwise derivatized, as in claim 3.
Claim 26 recites functionalized variants of vaccines based on peptides, proteins, RNA, or DNA. As best understood by the examiner, the term “functionalized variant” refers to peptides, proteins, RNA, or DNA that has been chemically modified. This is discussed as of the top paragraph on page 15 of the specification, which provides the example of cholesterol and lipid modified DNA or RNA. As best understood by the examiner, proteins and peptides subject to post-translational modifications are also understood to be functionalized variants of proteins and peptides.
As to claim 33, the phrase “the lipid” is understood to refer to the lipid material that makes up the lipid bilayer of claim 1, and is therefore understood to have appropriate antecedent basis. The phrase “the polysaccharide” is understood to refer to the hydrophobically modified polysaccharide recited by claim 1.
The examiner takes the position that applicant does not appear to dispute these claim interpretations, as of applicant’s response on 23 October 2025.
Claim Rejections - 35 USC § 103 – Obviousness
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.
Claim(s) 1-4, 7-9, 11, 13-14, 16-18, 20, 22, 25, 28, and 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ramamoorthy et al. (US 2019/0154698 A1) in view of Ravula et al. (Langmuir, Vol. 33, 2017, pages 10655-10662 and S1-S4) and Morros et al. (Carbohydrate Polymers, Vol. 81, 2010, pages 681-686).
Ramamoorthy et al. (hereafter referred to as Ramamoorthy) is drawn to a lipid bilayer having two opposing hydrophilic faces and a hydrophilic edge between the hydrophilic faces, as of Ramamoorthy, title, abstract, and figure in abstract, reproduced below.
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The composition includes a copolymer encircling the hydrophobic edge, wherein said copolymer has a first monomeric unit including a pendant aromatic or alkyl groups and a second monomeric unit including a hydrophilic groups.
Ramamoorthy differs from the claimed invention because a copolymer having a first monomeric unit including a pendant aromatic or alkyl groups and a second monomer unit including a hydrophilic groups is not a polysaccharide modified with a hydrophobic group.
Ravula et al. (hereafter referred to as Ravula) is drawn to polymer lipid nanodiscs, as of Ravula, page 10655, title, abstract, and figure in abstract, reproduced below.
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Ravula also teaches the following as of page 10655, left column, relevant text reproduced below.
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As such, the above-reproduced text indicates that amphiphilic polymers are generally suitable for the formation of nanodiscs. Ravula teaches that styrene maleic anhydride copolymer is a useful polymer for the formation of nanodiscs; however, Ravula indicates problems with styrene maleic anhydride copolymer regarding stability under conditions of high acid or high amounts of divalent metal cations, as of Ravula, page 10655, right column.
Neither Ravula nor Ramamoorthy teach a polysaccharide modified with hydrophobic groups.
Morros et al. (hereafter referred to as Morros) is drawn to hydrophobically modified derivatives of the polysaccharide known as inulin, as of Morros, page 681, title and abstract [NOTE: inulin is not the same as insulin, because inulin is a polysaccharide and insulin is a peptide]. Also see Morros, figures 1 and 2, reproduced below.
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These hydrophobically modified polysaccharides are amphiphilic polymers, as of Morros, page 681, paragraph bridging left and right columns.
Morros does not teach a nanodisc.
It would have been prima facie obvious for one of ordinary skill in the art to have substituted the hydrophobically modified inulin of Morros in place of the copolymer of Ramamoorthy for use in stabilizing a nanodisc such as that of Ramamoorthy or Ravula. Ramamoorthy and Ravula are drawn to a lipid nanodisc which combines a lipid and a copolymer. Ramamoorthy teaches that the copolymer must specifically be that including two monomeric units wherein one includes a pendant aromatic group and the other includes a pendant hydrophilic group, apparently referring to this as an amphiphilic belt in paragraph 0004. Nevertheless, Ravula teaches that other amphiphilic polymers can be used to form nanodiscs, as of Ravula, page 10655, left column. Morros teaches hydrophobically modified inulins, and these are amphiphilic polymers because they comprise a hydrophilic inulin portion and a hydrophobic long alkyl or aryl portion. As such, the skilled artisan would have been motivated to have substituted the hydrophobically modified inulins of Morros in place of the copolymer of Ramamoorthy for predictable formation of a nanodisc with a reasonable expectation of success. The simple substitution of one known element (e.g. the hydrophobically derivatized inulin of Morros) in place of another (the polymer of Ramamoorthy) in order to have achieved predictable results (both polymers would have predictably stabilized a lipid nanodisc because both are amphiphilic) is prima facie obvious. See MPEP 2143, Exemplary Rationale B.
As to claim 1, Ramamoorthy and Ravula teach the required lipid bilayer and Morros teaches the required polymer.
As to claim 1, the claim requires between 5% and 15% of the original hydroxyl groups to be modified; see the above rejection under 25 U.S.C. 112(b). Morros teaches examples wherein there was a 16%, 22%, and 23% efficiency in alkylating inulin, as of Morros, page 683, Table 2, reproduced below.
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These values slightly exceed the claimed maximum of 15%. Nevertheless, Morros teaches the general concept of the degree of substitution as of page 684, section 2.4. As such, the skilled artisan would have been motivated to have modified the degree of substitution of the polysaccharide of Morros. Where 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 MPEP 2144.05(II)(A). In this case, the general conditions of a substituted polysaccharide have been taught by Morros. As such, it would not have been inventive for the skilled artisan to have discovered the optimum or workable ranges of degree of substitution by routine experimentation.
As to claim 2, Morros teaches that inulin has a degree of polymerization of about 25, as of Morros, page 682, right column, section 2.1. The polymer appears to be linear as of the structure shown on page 682, figure 1 of Morros.
As to claim 3, Morros teaches inulin, as of the title of the reference.
As to claim 4, Morros teaches C7, C11, and C13 alkyl chains as of page 682, left column, figure 2, items c, d, and e.
As to claim 7, Morros teaches derivatization of inulin with phenyl glycidyl ether, as of page 682, right column, section 2.1 as well as page 682, left column, figure 2, item (a). This would have resulted in inulin being modified with phenyl groups.
As to claim 8, the structure of Morros does not appear to comprise amines.
As to claim 9, the hydrophobic group appears to be bound to the inulin of Morros via an ether group that is formed via epoxide ring opening; see e.g. Morros, page 682, figure 3, reproduced below.
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As to claim 11, the polymer of Morros does not appear to include charged groups such as carboxylic acids or amines; as such, the skilled artisan would have expected this polymer to have been free of charge in the claimed range.
As to claim 13, the molecular weight of fructose, which is the monomer from which inulin is made, is about 180 Daltons. Therefore, a degree of polymerization of 25 would have resulted in a molecular weight of about 4500 Daltons, or 4.5 kg/mol. The skilled artisan would have expected this molecular weight to have increased upon hydrophobic derivatization due to the molecular weight of the added hydrophobic groups. Regardless, where 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 MPEP 2144.05(II)(A). In this case, the general conditions of an amphiphilic polymer have been taught by the prior art. As such, it would not have been inventive for the skilled artisan to have determined the optimum or workable range of the molecular weight of the amphiphilic polymer by routine experimentation.
As to claim 14, Ramamoorthy teaches various lipid such as phosphatidylcholines and phosphatidylglycerols, as of Ramamoorthy, paragraph 0036.
As to claim 16, Ramamoorthy teaches a natural cell membrane extract, as of paragraph 0036.
As to claim 17, Ramamoorthy teaches the following in paragraph 0039, relevant text reproduced below.
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As such, the skilled artisan would have been motivated to have optimized the ratio of the lipids to the amphiphilic copolymer (which in this case is a polysaccharide) in order to have predictably altered the size of the composition with a reasonable expectation of success. Ramamoorthy also teaches a weight ratio in the range of about 3:1 to about 1:3 in paragraph 0049; this overlaps with the claimed range. While the prior art does not disclose the exact claimed values, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. See MPEP 2144.05(I).
As to claim 18, Ramamoorthy teaches a diameter of about 6 nm to about 100 nm in paragraph 0039.
As to claim 20, the skilled artisan would have expected the composition of Ramamoorthy when modified to remove the styrene-maleic anhydride and to replace that with the polymer of Morros to have been stable in the required amount of divalent ion. This is because such a polymer would not have had carboxylic groups that would have been destabilized in the presence of divalent ion. See the Ravula reference, which discusses this issue in detail on the paragraph bridging pages 10655-10656.
As to claim 22, Ramamoorthy teaches a membrane protein spanning across the entire lipid bilayer from the first hydrophilic face to the second hydrophilic face more than once, as of paragraph 0041 of Ramamoorthy.
As to claim 25, Ramamoorthy teaches drug delivery in paragraph 0055; as such, the skilled artisan would have been motivated to have included a drug.
As to claim 28, Ramamoorthy teaches characterizing a membrane protein as of the last sentence of the abstract, as well as paragraphs 0051-0056.
As to claim 33, Ramamoorthy teaches contacting the lipid and copolymer in paragraphs 0006 and 0009.
Note Regarding Filing Date: The instant application claims benefit to provisional application 63/198,640, filed on 30 October 2020. Ramamoorthy was published in May 2019. As such, Ramamoorthy is prior art under AIA 35 U.S.C. 102(a)(1). The exceptions under AIA 35 U.S.C. 102(b)(1)(A) and 102(b)(1)(B) would not appear to be applicable here because Ramamoorthy was published over a year prior to the effective filing date of the instant application.
Claim(s) 25-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ramamoorthy et al. (US 2019/0154698 A1) in view of Ravula et al. (Langmuir, Vol. 33, 2017, pages 10655-10662 and S1-S4) and Morros et al. (Carbohydrate Polymers, Vol. 81, 2010, pages 681-686), the combination further in view of Kuai et al. (Nature Materials, Vol. 16, April 2017, pages 489-496 and two additional pages).
Ramamoorthy and Ravula are drawn to a lipid nanodisc comprising an amphiphilic polymer. Morros teaches a hydrophobically modified polysaccharide as the amphiphilic polymer. See the above rejection over Ramamoorthy, Ravula, and Morros by themselves. Ramamoorthy teaches drug delivery as of paragraph 0055.
Ramamoorthy does not teach delivery of a vaccine.
Kuai et al. (hereafter referred toas Kuai) is drawn to nanodiscs for delivering peptides used as cancer vaccines for cancer immunotherapy, as of Kuai, page 489, title and abstract. The nanodiscs appear useful for delivery of said vaccines, as of Kuai, page 490, figure 1, reproduced below.
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Kuai does not teach a hydrophobically derivatized polysaccharide.
It would have been prima facie obvious for one of ordinary skill in the art to have used the nanodisc of Ramamoorthy in view of Ravula and as modified by Morros to have delivered the vaccines of Kuai. Ramamoorthy is drawn to the use of nanodiscs for drug delivery, as of Ramamoorthy, paragraph 0055. However, Ramamoorthy does not specify the drug to be delivered. Kuai teaches that nanodiscs can be used to delivery vaccines. As such, the skilled artisan would have been motivated to have used the nanodisc of Ramamoorthy in view of Ravula and as modified by Morros to have predictably delivered the vaccine of Kuai with a reasonable expectation of success.
Response to Arguments Regarding Obviousness Rejections
Applicant has made arguments regarding the previously applied rejection, as of applicant’s response on 23 October 2025 (hereafter referred to as applicant’s response). These arguments are addressed below.
In applicant’s response, page 6, second paragraph, applicant makes the following arguments.
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This is not persuasive. Morros teaches the general concept of degree of substitution, as of Morros, page 684, section 2.4. Morros teaches examples wherein there was a 16%, 22%, and 23% efficiency in alkylating inulin, as of Morros, page 683, Table 2, reproduced below.
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These values slightly exceed the claimed maximum of 15%. Nevertheless, Morros teaches the general concept of the degree of substitution as of page 684, section 2.4. As such, the skilled artisan would have been motivated to have modified the degree of substitution of the polysaccharide of Morros. Where 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 MPEP 2144.05(II)(A). In this case, the general conditions of a substituted polysaccharide have been taught by Morros. As such, it would not have been inventive for the skilled artisan to have discovered the optimum or workable ranges of degree of substitution by routine experimentation.
Applicant then presents results drawn to alleged unexpectedly improved results, as of applicant’s response, pages 6-7, relevant text reproduced in part below.
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The above-reproduced text appears to rely upon data presented in a post-filing date publication to show apparent unexpected results. However, the data from the post-filing date publication has not been submitted in the form of an affidavit or declaration. Objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. See MPEP 716.01(c)(I). As the above-indicated data has not been presented in the form of an affidavit or declaration, it cannot be probative of non-obviousness.
With that being said, it appears that the above-indicated argument references a comparison to a comparative example that is closer than the closest subject matter to actually exist in the prior art. See MPEP 716.02(e). The above-indicated references an unexpected and superior result at certain levels of hydrophobic modification that does not exist at lower or higher levels of hydrophobic modification. This appears to be a significant improvement that would not have been expected by one of ordinary skill in the art. As such, the above-indicated arguments would appear to show that, were the described experiments to be presented in the form of an affidavit or declaration, such an affidavit or declaration would likely be probative of non-obviousness.
Non-Statutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 7-9, 11, 13-14, 16-18, 20, 22, 25-26, 28, and 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,092,605 in view of Ravula et al. (Langmuir, Vol. 33, 2017, pages 10655-10662 and S1-S4) and Morros et al. (Carbohydrate Polymers, Vol. 81, 2010, pages 681-686).
Claims 1-4, 7-9, 11, 13-14, 16-18, 20, 22, 25-26, 28, and 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,813,358 in view of Ravula et al. (Langmuir, Vol. 33, 2017, pages 10655-10662 and S1-S4) and Morros et al. (Carbohydrate Polymers, Vol. 81, 2010, pages 681-686).
Claims 1-4, 7-9, 11, 13-14, 16-18, 20, 22, 25-26, 28, and 33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,050,227 in view of Ravula et al. (Langmuir, Vol. 33, 2017, pages 10655-10662 and S1-S4) and Morros et al. (Carbohydrate Polymers, Vol. 81, 2010, pages 681-686).
The instant claims are drawn to a lipid nanodisc composition. Said composition comprises a lipid bilayer with first and second hydrophilic faces and a hydrophobic edges between the hydrophilic faces, as well as a hydrophobically modified polysaccharide encircling the hydrophobic edges of the lipid bilayer.
The conflicting claims of all of the above-indicated patents are drawn to a lipid nanodisc composition. Said composition comprises a lipid bilayer with first and second hydrophilic faces and a hydrophobic edges between the hydrophilic faces in all of the above-indicated patents. Said composition also comprises a polymer. Said polymer is a copolymer comprising aromatic and hydrophilic units in the ‘605 patent, a copolymer comprising hydrophobic acrylic and hydrophilic units in the ‘358 patent, and comprising hydrophobic non-aromatic acryloyl groups and hydrophilic groups in the ‘227 patent.
The conflicting claims differ from the claimed invention because the polymers recited by the claims of the above-indicated patents differ from the claimed polymer of a hydrophobically modified polysaccharide.
Ravula et al. (hereafter referred to as Ravula) is drawn to polymer lipid nanodiscs, as of Ravula, page 10655, title, abstract, and figure in abstract, reproduced below.
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Ravula also teaches the following as of page 10655, left column, relevant text reproduced below.
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As such, the above-reproduced text indicates that amphiphilic polymers are generally suitable for the formation of nanodiscs. Ravula teaches that styrene maleic anhydride copolymer is a useful polymer for the formation of nanodiscs; however, Ravula indicates problems with this particular polymer regarding stability under conditions of high acid or high amounts of divalent metal cations, as of Ravula, page 10655, right column.
Neither Ravula nor Ramamoorthy teach a polysaccharide modified with hydrophobic groups.
Morros et al. (hereafter referred to as Morros) is drawn to hydrophobically modified derivatives of the polysaccharide known as inulin, as of Morros, page 681, title and abstract [NOTE: inulin is not the same as insulin, because inulin is a polysaccharide and insulin is a peptide]. Also see Morros, figures 1 and 2, reproduced below.
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These hydrophobically modified polysaccharides are amphiphilic polymers, as of Morros, page 681, paragraph bridging left and right columns.
Morros does not teach a nanodisc.
It would have been prima facie obvious for one of ordinary skill in the art to have substituted the hydrophobically modified inulin of Morros in place of the copolymer of the conflicting claims for use in stabilizing the nanodisc of the conflicting claims. Both the conflicting claims and Ravula are drawn to a lipid nanodisc which combines a lipid and a copolymer. The conflicting claims recite different copolymers that can be used to stabilize a lipid nanodisc. Nevertheless, Ravula teaches that other amphiphilic polymers can be used to form nanodiscs, as of Ravula, page 10655, left column. Morros teaches hydrophobically derivatized inulins, and these are amphiphilic polymers because they comprise a hydrophilic inulin portion and a hydrophobic long alkyl or aryl portion. As such, the skilled artisan would have been motivated to have substituted the hydrophobically derivatized inulins of Morros in place of the copolymer of the conflicting claims for predictable formation of a nanodisc with a reasonable expectation of success. The simple substitution of one known element (e.g. the hydrophobically derivatized inulin of Morros) in place of another (the polymers of the conflicting claims) in order to have achieved predictable results (both polymers would have predictably stabilized a lipid nanodisc because both are amphiphilic) is prima facie obvious. See MPEP 2143, Exemplary Rationale B.
As to the newly added limitation of claim 1 regarding the 5% to 15% of the hydroxyl groups that have been modified by hydrophobic functionalization, Morros teaches the general concept of degree of substitution, as of Morros, page 684, section 2.4. Morros teaches examples wherein there was a 16%, 22%, and 23% efficiency in alkylating inulin, as of Morros, page 683, Table 2, reproduced below.
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422
1316
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These values slightly exceed the claimed maximum of 15%. Nevertheless, Morros teaches the general concept of the degree of substitution as of page 684, section 2.4. As such, the skilled artisan would have been motivated to have modified the degree of substitution of the polysaccharide of Morros. Where 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 MPEP 2144.05(II)(A). In this case, the general conditions of a substituted polysaccharide have been taught by Morros. As such, it would not have been inventive for the skilled artisan to have discovered the optimum or workable ranges of degree of substitution by routine experimentation.
Response to Arguments Regarding Double Patenting Rejection
Applicant makes the following arguments regarding the previously applied double patenting rejection, as of applicant’s response, page 8, relevant text reproduced below.
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628
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Even, purely en arguendo, it is correct that the claims of the above-cited patents do not recite 5% to 15% of the hydroxyl groups of the polysaccharide having been functionalized, the skilled artisan would have been motivated to have modified the composition of the conflicting claims to have achieved this in view of Ravula and Morros. Applicant’s argument appears to address the conflicting claims by themselves, not the conflicting claims in view of Ravula and Morros. One cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references. See MPEP 2145(IV).
Relevant Prior Art – No Rejection
As additional relevant prior art that has not previously been cited in the file record, the examiner cites Irvine et al. (US 2023/0149560 A1), which was effectively filed prior to the effective filing date of the instant application. Irvine et al. (hereafter referred to as Irvine) is drawn to lipid nanodiscs, as of Irvine, title and abstract. Irvine teaches the inclusion of a polymer-modified lipid, apparently as part of the nanodisc, as of Irvine, paragraph 0317, wherein the polymer may be a polysaccharide, as of paragraph 0317 of Irvine. With that being said, Irvine does not appear to exemplify a nanodisc comprising a polysaccharide in which 5% to 15% of the functional groups that were hydroxyl groups presented in the original polysaccharide have been hydrophobically modified. Additionally, the modifications discussed in paragraphs 0317-0320 of Irving appear to be modification with a hydrophilic polymer such as PEG, not modification of a polysaccharide with multiple hydroxyl groups to be more hydrophobic. As such, the teachings of Irvine at best appear to suggest the inclusion of a hydrophobically modified polysaccharide in a lipid nanodisc, but not actually explicitly teach this in an example.
As such, the examiner does not understand Irvine to be anticipatory. The examiner understands Irvine to be just as good as, but no better than, the Ramamoorthy, Ravula, and Morros references cited in the applied rejection. In selecting the references to be used in rejecting the claims, the examiner should carefully compare the references with one another and with the applicant’s disclosure to avoid an unnecessary number of rejections over similar references. The examiner is not called upon to cite all references that may be available, but only the "best." (See 37 CFR 1.104(c).) Multiplying references, any one of which is as good as, but no better than, the others, adds to the burden and cost of prosecution and should therefore be avoided. See MPEP 904.03.
Conclusion
No claim is allowed.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612