DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicants’ submission filed on 2/2/2026 has been entered.
Claims Status
Applicants’ amendment filed February 20, 2026, is acknowledged. Claim 1 has been amended. Claims 14-21 have been currently withdrawn- currently amended. Claim 2 has been previously presented. Claims 5-13 are original. Claims 3-4 have been canceled. Claims 1-2 and 5-13 are under examination.
Rejection Withdrawn
The following rejection is withdrawn from the Office Action filed February 20, 2026, based on Applicant’s arguments.
The rejection of claims 1-2 and 5-13 under 35 U.S.C.102(a)(1), pages 3-4 of
the previous Office action.
Trademarks
The use of the term for example, Qiagen, page 21 which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Please, review the specification, for other trademarks. Correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2 and 5-13 are rejected under 35 U.S.C. 102(a) (1) and 102(a)(2) as anticipated by Grandi et al (WO 2019/170837 published September 12, 2019, filed March 9, 2018).
Claim 1 is drawn to a therapeutic composition comprising: a commensal bacterial outer membrane vesicle (OMV) loaded with a therapeutic moiety that is exogenous to the OMV, wherein the commensal bacterial OMV is from a bacterial genera selected from Akkermansia, or Veillonella, or an Escherichia coli bacterial species selected from DH5-alpha, 541-15, 568-2, T75, LF82, 79, 88, 117, 128, 132, 142, 143, 147, 149, UM-146, HM427, HM428, HM452, HM454, HM455, HM456, HM463, HM484, HM488, HM489, HM615, 4F, 13I, 30A, 150F, NRG857c.
Claim 2 is drawn to therapeutic composition of claim 1, wherein the commensal bacterial OMV is from a bacterium that is a resident of the gut, a bacterium that is not intergeneric, or a gram-negative bacterial species.
Claim 5 is drawn to the therapeutic composition of claim 1, wherein the commensal bacterial OMV has a diameter of about 50 nm to about 300 nm.
Claims 6 is drawn to the therapeutic composition of claim 1, wherein the commensal bacterial OMV is a purified or isolated commensal bacterial OMV.
Claim 7 is drawn the therapeutic composition of claim 1, wherein the commensal bacterial OMV is enriched compared to the commensal bacterial culture.
Claim 8 is drawn to the therapeutic composition of claim 1, wherein the therapeutic moiety is selected from a nucleic acid, a protein, a chemical, a drug, or a small molecule.
Claim 9 is drawn to the therapeutic composition of claim 8, wherein the nucleic acid encodes a protein selected from a therapeutic protein, a transcriptional activator, or a transcriptional repressor.
Claim 10 is drawn to the therapeutic composition of claim 9, wherein the therapeutic protein is selected from a cytokine, an antigen, an antibody, a biologic, a growth factor, an enzyme, a differentiation factor, an immune modulating factor, or a vaccination protein.
Claim 11 is drawn to the therapeutic composition of claim 8, wherein the drug is an antibiotic, a biologic, a steroid, a chemotherapeutic, or an immunosuppressant.
Claim 12 is drawn to the therapeutic composition of claim 1, further comprising a pharmaceutically acceptable carrier.
Claim 13 is drawn to the therapeutic composition of claim 1, wherein the therapeutic composition is formulated as a tablet, suspension, a capsule, or other suitable formulation for oral delivery.
Grandi et al teach that all gram-negative bacteria spontaneously release membrane vesicles (OMVs) during vitro and in vivo (page 4). Grandi et al teach OMVs have been purified from Gram-negative bacteria, including species from any of genera Escherichia, Shigella, Neisseria, Moraxella, Bordetella, Borrelia, Brucella, Chlamydia, Haemophilus, Legionella, Pseudomonas, Yersinia, Helicobacter, Salmonella, Vibrio, etc. For example, the vesicles may be from Bordetella pertussis, Borrelia burgdorferi, Brucella melitensis, Brucella ovis, Chlamydia psittaci, Chlamydia trachomatis, Moraxella catarrhalis, Escherichia coli (including extraintestinal pathogenic strains), Haemophilus influenzae (including non-typeable stains), Legionella pneumophila, Neisseria gonorrhoeae, Neisseria meningitidis, Neisseria lactamica, Pseudomonas aeruginosa, Yersinia enterocolitica, Helicobacter pylori, Salmonella enterica (including serovar typhi and typhimurium), Vibrio cholerae, Shigella dysenteriae, Shigella flexneri, Shigella boydii or Shigella sonnei (page 18). Grandi et al teach a method of preparing isolated bacterial outer membrane vesicles expressing heterologous proteins (pages 7-8 and 14-18). Grandi et al teach therapeutic proteins and compositions (pages 18-20). Grandi et al teach therapeutic compositions that are formulated injectables, solutions or suspensions (page 19). Grandi et al anticipate the claimed invention. Grandi et al teach that OMVs are 20 -300 nm in diameter (page 4). Grandi et al anticipate the claimed invention.
Claims 1-2 and 5-13 are rejected under 35 U.S.C. 102(a)(2) as anticipated by Grandi et al (WO 2020/212524 A1 published October 22, 2020, priority April 18, 2019).
Claim 1 is drawn to a therapeutic composition comprising: a commensal bacterial outer membrane vesicle (OMV) loaded with a therapeutic moiety that is exogenous to the OMV, wherein the commensal bacterial OMV is from a bacterial genera selected from Akkermansia, or Veillonella, or an Escherichia coli bacterial species selected from DH5-alpha, 541-15, 568-2, T75, LF82, 79, 88, 117, 128, 132, 142, 143, 147, 149, UM-146, HM427, HM428, HM452, HM454, HM455, HM456, HM463, HM484, HM488, HM489, HM615, 4F, 13I, 30A, 150F, NRG857c.
Claim 2 is drawn to therapeutic composition of claim 1, wherein the commensal bacterial OMV is from a bacterium that is a resident of the gut, a bacterium that is not intergeneric, or a gram-negative bacterial species.
Claim 5 is drawn to the therapeutic composition of claim 1, wherein the commensal bacterial OMV has a diameter of about 50 nm to about 300 nm.
Claims 6 is drawn to the therapeutic composition of claim 1, wherein the commensal bacterial OMV is a purified or isolated commensal bacterial OMV.
Claim 7 is drawn the therapeutic composition of claim 1, wherein the commensal bacterial OMV is enriched compared to the commensal bacterial culture.
Claim 8 is drawn to the therapeutic composition of claim 1, wherein the therapeutic moiety is selected from a nucleic acid, a protein, a chemical, a drug, or a small molecule.
Claim 9 is drawn to the therapeutic composition of claim 8, wherein the nucleic acid encodes a protein selected from a therapeutic protein, a transcriptional activator, or a transcriptional repressor.
Claim 10 is drawn to the therapeutic composition of claim 9, wherein the therapeutic protein is selected from a cytokine, an antigen, an antibody, a biologic, a growth factor, an enzyme, a differentiation factor, an immune modulating factor, or a vaccination protein.
Claim 11 is drawn to the therapeutic composition of claim 8, wherein the drug is an antibiotic, a biologic, a steroid, a chemotherapeutic, or an immunosuppressant.
Claim 12 is drawn to the therapeutic composition of claim 1, further comprising a pharmaceutically acceptable carrier.
Claim 13 is drawn to the therapeutic composition of claim 1, wherein the therapeutic composition is formulated as a tablet, suspension, a capsule, or other suitable formulation for oral delivery.
Grandi et al teach that all gram-negative bacteria spontaneously release membrane vesicles (OMVs) during in vitro and in vivo (page 1). Grandi et al teach OMVs have been purified from Neisseria, Salmonella, Pseudomonas, Vibrio cholerae, Burkholeria and E. coli to name a few (page 2). Grandi et al teach OMVs from Shigella as well (page 8). Grandi et al teach a method of preparing isolated bacterial outer membrane vesicles expressing heterologous proteins (page 8). Grandi et al teach therapeutic proteins and compositions (pages 11-15). Grandi et al teach therapeutic compositions that are formulated injectables, solutions or suspensions (page 14). Grandi et al anticipate the claimed invention.
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.
Claims 1-2 and 5-13 are rejected under 35 U.S.C. 103 as being unpatentable over Lu et al (US Publication 2017/0145061 A1) in view of Grandi et al (WO 2020/212524 A1 published October 2020, priority April 18, 2019).
Claim 1 is drawn to a therapeutic composition comprising: a commensal bacterial outer membrane vesicle (OMV) loaded with a therapeutic moiety that is exogenous to the OMV, wherein the commensal bacterial OMV is from a bacterial genera selected from Akkermansia, or Veillonella, or an Escherichia coli bacterial species selected from DH5-alpha, 541-15, 568-2, T75, LF82, 79, 88, 117, 128, 132, 142, 143, 147, 149, UM-146, HM427, HM428, HM452, HM454, HM455, HM456, HM463, HM484, HM488, HM489, HM615, 4F, 13I, 30A, 150F, NRG857c.
Claim 2 is drawn to therapeutic composition of claim 1, wherein the commensal bacterial OMV is from a bacterium that is a resident of the gut, a bacterium that is not intergeneric, or a gram-negative bacterial species.
Claim 5 is drawn to the therapeutic composition of claim 1, wherein the commensal bacterial OMV has a diameter of about 50 nm to about 300 nm.
Claims 6 is drawn to the therapeutic composition of claim 1, wherein the commensal bacterial OMV is a purified or isolated commensal bacterial OMV.
Claim 7 is drawn the therapeutic composition of claim 1, wherein the commensal bacterial OMV is enriched compared to the commensal bacterial culture.
Claim 8 is drawn to the therapeutic composition of claim 1, wherein the therapeutic moiety is selected from a nucleic acid, a protein, a chemical, a drug, or a small molecule.
Claim 9 is drawn to the therapeutic composition of claim 8, wherein the nucleic acid encodes a protein selected from a therapeutic protein, a transcriptional activator, or a transcriptional repressor.
Claim 10 is drawn to the therapeutic composition of claim 9, wherein the therapeutic protein is selected from a cytokine, an antigen, an antibody, a biologic, a growth factor, an enzyme, a differentiation factor, an immune modulating factor, or a vaccination protein.
Claim 11 is drawn to the therapeutic composition of claim 8, wherein the drug is an antibiotic, a biologic, a steroid, a chemotherapeutic, or an immunosuppressant.
Claim 12 is drawn to the therapeutic composition of claim 1, further comprising a pharmaceutically acceptable carrier.
Claim 13 is drawn to the therapeutic composition of claim 1, wherein the therapeutic composition is formulated as a tablet, suspension, a capsule, or other suitable formulation for oral delivery.
Lu et al disclose of human gut commensals of Bacteroides species to secrete heterologous therapeutic proteins via outer membrane vesicles. (See abstract; claims). Lu et al further disclose the OMVs to have a diameter ranging from 20 to 250 nm. (See paragraph 0033). Lu et al further disclose the therapeutic protein to be an antibody, cytokine or growth factor. (See claim 12). Lu et al disclose of administering the OMVs comprising a therapeutic protein via oral administration. (See paragraph 0059).
Lu et al do not specifically teach the claim limitation “wherein the commensal bacterial OMV is from a bacterial genera selected from Akkermansia, or Veillonella, or an Escherichia coli bacterial species selected from DH5-alpha, 541-15, 568-2, T75, LF82, 79, 88, 117, 128, 132, 142, 143, 147, 149, UM-146, HM427, HM428, HM452, HM454, HM455, HM456, HM463, HM484, HM488, HM489, HM615, 4F, 13I, 30A, 150F, NRG857c”.
However, Grandi et al teach that all gram-negative bacteria spontaneously release membrane vesicles (OMVs) during in vitro and in vivo (page 1). Grandi et al teach OMVs have been purified from Neisseria, Salmonella, Pseudomonas, Vibrio cholerae, Burkholeria and E. coli to name a few (page 2). Grandi et al teach OMVs from Shigella as well (page 8). Grandi et al teach a method of preparing isolated bacterial outer membrane vesicles expressing heterologous proteins (page 8). Grandi et al teach therapeutic proteins and compositions (pages 11-15). Grandi et al teach therapeutic compositions that are formulated injectables, solutions or suspensions (page 14).
It would be prima facie obvious at the time the invention was made to combine the teachings of Lu et al with the teachings Grandi et al to arrive at a therapeutic composition comprising: a commensal bacterial outer membrane vesicle (OMV) loaded with a therapeutic moiety that is exogenous to the OMV, wherein the commensal bacterial OMV is from a bacterial genera selected from Akkermansia, or Veillonella, or an Escherichia coli bacterial species because Lu et al disclose of human gut commensals of specifically Bacteroides species to secrete heterologous therapeutic proteins via outer membrane vesicles and however, Grandi et al teach that all gram-negative bacteria spontaneously release membrane vesicles (OMVs) during in vitro and in vivo (page 1). Grandi et al teach OMVs have been purified from Neisseria, Salmonella, Pseudomonas, Vibrio cholerae, Burkholeria and E. coli to name a few (page 2). One of ordinary skill in the art would expect a reasonable expectation of success to prepare a therapeutic composition comprising: a commensal bacterial outer membrane vesicle (OMV) loaded with a therapeutic moiety that is exogenous to the OMV by substituting the Bacteroides OMVs as taught by Lu et al with gram-negative OMVs of Grandi et al because Grandi et al has demonstrated that all gram-negative bacterial can be used to prepare heterologous therapeutic compositions. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02). The combination of art references renders the claimed invention obvious.
Claims 1-2 and 5-13 are rejected under 35 U.S.C. 103 as being unpatentable over Lu et al (US Publication 2017/0145061 A1) in view of Grandi et al (WO 2019/170837 published September 12, 2019, filed March 9, 2018).
Claim 1 is drawn to a therapeutic composition comprising: a commensal bacterial outer membrane vesicle (OMV) loaded with a therapeutic moiety that is exogenous to the OMV, wherein the commensal bacterial OMV is from a bacterial genera selected from Akkermansia, or Veillonella, or an Escherichia coli bacterial species selected from DH5-alpha, 541-15, 568-2, T75, LF82, 79, 88, 117, 128, 132, 142, 143, 147, 149, UM-146, HM427, HM428, HM452, HM454, HM455, HM456, HM463, HM484, HM488, HM489, HM615, 4F, 13I, 30A, 150F, NRG857c.
Claim 2 is drawn to therapeutic composition of claim 1, wherein the commensal bacterial OMV is from a bacterium that is a resident of the gut, a bacterium that is not intergeneric, or a gram-negative bacterial species.
Claim 5 is drawn to the therapeutic composition of claim 1, wherein the commensal bacterial OMV has a diameter of about 50 nm to about 300 nm.
Claims 6 is drawn to the therapeutic composition of claim 1, wherein the commensal bacterial OMV is a purified or isolated commensal bacterial OMV.
Claim 7 is drawn the therapeutic composition of claim 1, wherein the commensal bacterial OMV is enriched compared to the commensal bacterial culture.
Claim 8 is drawn to the therapeutic composition of claim 1, wherein the therapeutic moiety is selected from a nucleic acid, a protein, a chemical, a drug, or a small molecule.
Claim 9 is drawn to the therapeutic composition of claim 8, wherein the nucleic acid encodes a protein selected from a therapeutic protein, a transcriptional activator, or a transcriptional repressor.
Claim 10 is drawn to the therapeutic composition of claim 9, wherein the therapeutic protein is selected from a cytokine, an antigen, an antibody, a biologic, a growth factor, an enzyme, a differentiation factor, an immune modulating factor, or a vaccination protein.
Claim 11 is drawn to the therapeutic composition of claim 8, wherein the drug is an antibiotic, a biologic, a steroid, a chemotherapeutic, or an immunosuppressant.
Claim 12 is drawn to the therapeutic composition of claim 1, further comprising a pharmaceutically acceptable carrier.
Claim 13 is drawn to the therapeutic composition of claim 1, wherein the therapeutic composition is formulated as a tablet, suspension, a capsule, or other suitable formulation for oral delivery.
Lu et al disclose of human gut commensals of Bacteroides species to secrete heterologous therapeutic proteins via outer membrane vesicles. (See abstract; claims). Lu et al further disclose the OMVs to have a diameter ranging from 20 to 250 nm. (See paragraph 0033). Lu et al further disclose the therapeutic protein to be an antibody, cytokine or growth factor. (See claim 12). Lu et al disclose of administering the OMVs comprising a therapeutic protein via oral administration. (See paragraph 0059).
Lu et al do not specifically teach the claim limitation “wherein the commensal bacterial OMV is from a bacterial genera selected from Akkermansia, or Veillonella, or an Escherichia coli bacterial species selected from DH5-alpha, 541-15, 568-2, T75, LF82, 79, 88, 117, 128, 132, 142, 143, 147, 149, UM-146, HM427, HM428, HM452, HM454, HM455, HM456, HM463, HM484, HM488, HM489, HM615, 4F, 13I, 30A, 150F, NRG857c”.
However, Grandi et al teach that all gram-negative bacteria spontaneously release membrane vesicles (OMVs) during in vitro and in vivo (page 4). Grandi et al teach OMVs have been purified from Gram-negative bacteria, including species from any of genera Escherichia, Shigella, Neisseria, Moraxella, Bordetella, Borrelia, Brucella, Chlamydia, Haemophilus, Legionella, Pseudomonas, Yersinia, Helicobacter, Salmonella, Vibrio, etc. For example, the vesicles may be from Bordetella pertussis, Borrelia burgdorferi, Brucella melitensis, Brucella ovis, Chlamydia psittaci, Chlamydia trachomatis, Moraxella catarrhalis, Escherichia coli (including extraintestinal pathogenic strains), Haemophilus influenzae (including non-typeable stains), Legionella pneumophila, Neisseria gonorrhoeae, Neisseria meningitidis, Neisseria lactamica, Pseudomonas aeruginosa, Yersinia enterocolitica, Helicobacter pylori, Salmonella enterica (including serovar typhi and typhimurium), Vibrio cholerae, Shigella dysenteriae, Shigella flexneri, Shigella boydii or Shigella sonnei (page 18). Grandi et al teach a method of preparing isolated bacterial outer membrane vesicles expressing heterologous proteins (pages 7-8 and 14-18). Grandi et al teach therapeutic proteins and compositions (pages 18-20). Grandi et al teach therapeutic compositions that are formulated injectables, solutions or suspensions (page 19). Grandi et al teach that OMVs are 20 -300 nm in diameter (page 4).
It would be prima facie obvious at the time the invention was made to combine the teachings of Lu et al with the teachings Grandi et al to arrive at a therapeutic composition comprising: a commensal bacterial outer membrane vesicle (OMV) loaded with a therapeutic moiety that is exogenous to the OMV, wherein the commensal bacterial OMV is from a bacterial genera selected from a number of gram-negative bacterial species because Lu et al disclose of human gut commensals of specifically Bacteroides species to secrete heterologous therapeutic proteins via outer membrane vesicles and however, Grandi et al teach that all gram-negative bacteria spontaneously release membrane vesicles (OMVs) during in vitro and in vivo (page 1).
One of ordinary skill in the art would expect a reasonable expectation of success to prepare a therapeutic composition comprising: a commensal bacterial outer membrane vesicle (OMV) loaded with a therapeutic moiety that is exogenous to the OMV by substituting the Bacteroides OMVs as taught by Lu et al with gram-negative OMVs of Grandi et al because Grandi et al has demonstrated that all gram-negative bacterial can be used to prepare heterologous therapeutic compositions. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02). The combination of art references renders the claimed invention obvious.
Status of Claims
No claims allowed.
Conclusion
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/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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