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 .
The amendment filed 06/11/2026 has been entered. Claims 1-16 have been cancelled. Claims 17-20 have been amended. Claims 21-26 have been added. Claims 17-26 are pending and are under examination.
Claim Rejections Withdrawn
The rejection of claim(s) 1-2, 5-10 and 12-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Betbeder et al. US 9,731,005 8/15/17 cited in IDS is withdrawn in view of the cancellation of the claims.
The rejection of claim(s) 1, 4-6, 16, 17 and 20 under 35 U.S.C. 102(a)(1) as being anticipated by Farokhzad et al. WO 2020/123661 6/18/2020 is withdrawn in view of the amendment to the claims.
The rejection of claim(s) 1-2, 5-10, 12 and 16 under 35 U.S.C. 102(a)(1) as being anticipated by Helou et al. PLOS Neglected Tropical Diseases https://doi.org/10.1371/journal.pntd.0009627 August 17, 2021 (19 pages) is withdrawn in view of the cancellation of the claims.
The rejection of claim(s) 1-2, 5-10 and 12-16 under 35 U.S.C. 102(a)(2) as being anticipated by Betbeder et al. US 2023/0338497 10/26/2023 with priority to PCT/FR2021/051270 filed 7/8/2021 is withdrawn in view of the cancellation of the claims.
The rejection of claim(s) 1-3 and 9-11 under 35 U.S.C. 103 as being unpatentable over Helou et al. PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0009627 August 17, 2021 (19 pages) in view of Doroud et al. Expert Rev. Vaccines 11(1), 69-86 (2012) is withdrawn in view of the cancellation of the claims.
The rejection of claim(s) 1-3 and 9-11 under 35 U.S.C. 103 as being unpatentable over Betbeder et al. US 9,731,005 8/15/17 cited in IDS in view of Doroud et al. Expert Rev. Vaccines 11(1), 69-86 (2012) is withdrawn in view of the cancellation of the claims.
The rejection of claims 1-2, 5-10 and 12-16 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/004980 (‘980) is withdrawn in view of the cancellation of the claims.
The rejection of claims 3 and 11 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/004980 (‘980) as applied to claims 1-2, 5-10 and 12-16 above, further in view of Doroud et al. Expert Rev. Vaccines 11(1), 69-86 (2012) is withdrawn in view of the cancellation of the claims.
The rejection of claim 4 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/004980 (‘980) as applied to claims 1-2, 5-10 and 12-16 above, further in view of Farokhzad et al. WO 2020/123661 6/18/2020 is withdrawn in view of the cancellation of the claims.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 17-18, 20-21 and 23-29 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Betbeder et al. US 9,731,005 8/15/17 cited in IDS.
Applicants argument regarding claim 17 have been carefully considered and are addressed in the rejection as set forth below.
Claim 17: Betbeder et al disclose a method of treating a patient infected with a disease or intracellular pathogen (col. 4 lines 62-65 defines patient as a warm-blooded animal such as a mammal which is afflicted with one or more disease and conditions described herein) that does not affect the central nervous system (a therapeutic vaccine) the method comprising administering to said patient infected (afflicted) with a disease or intracellular pathogen a therapeutically effective amount of a pharmaceutical vaccine described as for use in prophylactic treatment against an intracellular pathogenic agent in a patient which corresponds to the instant vaccine composition comprising at least one cationic nanoparticle including a porous solid cationic polysaccharide core loaded with an anionic phospholipid and a protein antigen specific to the pathogen or disease.
See column 2 lines 9-23. Column 2 lines 20 disclose prophylactic treatment against an in disease or infection caused by an intracellular pathogenic agent.
Column 2 lines 24-44 indicate the patient is infected with a disease or an intracellular pathogen.
4. For example, Betbeder defines “treatment” as “any decrease of the amount of the pathogenic agent in the patient's body or to any alteration of the pathogenic agent, even over a short time period. When the pathogenic agent has several forms including extracellular forms, a decrease or a modification of at least one pathogenic agent's form is considered as a treatment effect. If the pathogenic agent may be present in several organs of the patient's body, a decrease of the amount of pathogenic agent or a modification of the pathogenic agent in at least one organ is considered as a treatment effect.” Betbeder also discloses that the term “treating” includes “the administration of the composition of the invention to prevent or delay, to alleviate, or to arrest or inhibit development of the symptoms or conditions associated with a disease, condition or disorder as described herein.
5. Betbeder disclose the term “therapeutic” refers at least to the partial reduction, elimination, or prevention of the disease, symptoms of the disease, or side effects of the disease in the subject.”
6. Betbeder et al clearly discloses an embodiment when the treatment indicates that the patient is infected with the disease or intracellular pathogen. For example, in order to ameliorate the disease or decrease the amount of pathogenic agent in the patient’s body it means that the patient is infected with the disease or an intracellular pathogen Leishmania by to administering the pharmaceutical composition (vaccine composition).
7. Having established that many embodiments of “treatment” as defined by Betbeder clearly indicates that the patient is infected with disease or an intracellular pathogen that does not affect the central nervous system, the definition of “prophylactic treatment” by Betbeder “prophylactic” means that the treatment is able to prevent or delay the onset of the disease or is able to prevent manifestation of clinical or subclinical symptoms thereof” does not teach away from the definition of treatment. The definition of prophylactic does not state the patient is not infected with the disease or an intracellular pathogen that does not affect the central nervous system.
8. Applicants argument point to the definition of “prophylactic” but Applicants do not acknowledge that “treatment” is also defined in Betbeder and that Betbeder et al disclose the pharmaceutical composition is for use in the prophylactic treatment against an intracellular pathogenic agent in a patient or in the prophylactic treatment of a disease or infection caused by an intracellular pathogenic agent (column 2 lines 18-23). Since Betbeder discloses “prophylactic treatment”, the definition of “treatment” should be considered along with the definition of “prophylactic”.
9. The definition of “vaccine” as pointed out by Betbeder et al to mean “a product able to prevent infection caused by an intracellular pathogenic agent upon future exposure thereto” and example where the composition is used to prevent infection does not teach away from the clear teachings of Betbeder et al to have used the same composition for “prophylactic treatment”. Betbeder et al discloses a “vaccine” and also discloses a “prophylactic treatment”. Betbeder et al discloses both treatment and prevention.
10. Contrary to Applicants argument, Betbeder clearly and unequivocally disclose the step of administering to the patient infected with a disease or an intracellular pathogen the disclosed pharmaceutical composition. The embodiment of “treatment” in Betbeder et al disclose (and is not limited to) “if the pathogenic agent may be present in several organs of the patient's body, a decrease of the amount of pathogenic agent or a modification of the pathogenic agent in at least one organ is considered as a treatment effect.”
11. Betbeder et al defines “patient” (col. 4 lines 62-65) as “a warm-blooded animal such as a mammal which is afflicted with or has the potential to be afflicted with one or more disease and conditions described herein”.
12. Thus, the definition of “treatment” and “patient” by Betbeder et al expressly or inherently teaches each that the patient is infected with the disease or the intracellular pathogen.
Claim 18: Betbeder et al disclose the protein antigen is from Leishmania spp. See column 4 lines 40-55 and column 4 lines 13-27 particularly line 24.
Claim 20: Betbeder disclose that the porous solid cationic polysaccharide core is crosslinked and may be obtained by the reaction between a polysaccharide chosen from among starch, dextran, dextrin, and maltodextrin, derivatized with cationic ligands such as quaternary ammonium salts. Primary, secondary and tertiary amines may also be used. More particularly, the cationic polysaccharide can be obtained from the reaction between maltodextrin and glycidyl-trimethylammonium. See column 3 lines 30-37.
Claim 21: Betbeder discloses the protein antigen is from Leishmania spp which is responsible for Leishmaniasis. Col. 4 lines 44-61 and col. 4 lines 7-27.
Claim 23: Betbeder et al discloses the anionic phospholipid is diacyl phosphatidylglycerol, diacyl phosphatidylserine or diacyl phosphatidylinositol. See column 3 lines 38-42.
Claim 24: Betbeder disclose that the anionic phospholipid is dipalmitoylphosphatidylglycerol (DG). column 3 lines 38-42.
Claim 25: Betbeder et al disclose the protein antigen specific to the pathogen or disease is from a parasite. Col. 4 lines 44-61 and col. 4 lines 7-27.
Claim 26: Betbeder et al disclose the protein antigen is specific to a virus. Col. 4 lines 44-61 and column 3 lines 60-67.
Claim 27: Betbeder et al disclose the protein antigen is specific to a bacterium. Col. 4 lines 44-61 and column 3 lines 60-67.
Claim 28: Betbeder et al disclose the protein antigen is specific to a fungus. Col. 4 lines 44-61 and column 3 lines 60-67.
Claim 29: Betbeder disclose the vaccine composition is in a form suitable for mucosal (intranasal ) or injectable administration e.g. such as in liquid form. See column 5 lines 30-39 and lines 54-64.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
13. Claim(s) 17-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Betbeder et al. US 9,731,005 8/15/17 cited in IDS in view of Doroud et al. Expert Rev. Vaccines 11(1), 69-86 (2012).
Claim 17: Betbeder et al disclose a method of treating a patient infected with a disease or intracellular pathogen (col. 4 lines 62-65 defines patient as a warm-blooded animal such as a mammal which is afflicted with one or more disease and conditions described herein) that does not affect the central nervous system (a therapeutic vaccine) the method comprising administering to said patient infected (afflicted) with a disease or intracellular pathogen a therapeutically effective amount of a pharmaceutical vaccine described as for use in prophylactic treatment against an intracellular pathogenic agent in a patient which corresponds to the instant vaccine composition comprising at least one cationic nanoparticle including a porous solid cationic polysaccharide core loaded with an anionic phospholipid and a protein antigen specific to the pathogen or disease.
See column 2 lines 9-23. Column 2 lines 20 disclose prophylactic treatment against an in disease or infection caused by an intracellular pathogenic agent.
Column 2 lines 24-44 indicate the patient is infected with a disease or an intracellular pathogen.
For example, Betbeder defines “treatment” as “any decrease of the amount of the pathogenic agent in the patient's body or to any alteration of the pathogenic agent, even over a short time period. When the pathogenic agent has several forms including extracellular forms, a decrease or a modification of at least one pathogenic agent's form is considered as a treatment effect. If the pathogenic agent may be present in several organs of the patient's body, a decrease of the amount of pathogenic agent or a modification of the pathogenic agent in at least one organ is considered as a treatment effect.” Betbeder also discloses that the term “treating” includes “the administration of the composition of the invention to prevent or delay, to alleviate, or to arrest or inhibit development of the symptoms or conditions associated with a disease, condition or disorder as described herein.
Betbeder disclose the term “therapeutic” refers at least to the partial reduction, elimination, or prevention of the disease, symptoms of the disease, or side effects of the disease in the subject.”
Betbeder et al clearly discloses an embodiment when the treatment indicates that the patient is infected with the disease or intracellular pathogen. For example, in order to ameliorate the disease or decrease the amount of pathogenic agent in the patient’s body it means that the patient is infected with the disease or an intracellular pathogen Leishmania by to administering the pharmaceutical composition (vaccine composition).
Having established that many embodiments of “treatment” as defined by Betbeder clearly indicates that the patient is infected with disease or an intracellular pathogen that does not affect the central nervous system, the definition of “prophylactic treatment” by Betbeder “prophylactic” means that the treatment is able to prevent or delay the onset of the disease or is able to prevent manifestation of clinical or subclinical symptoms thereof” does not teach away from the definition of treatment. The definition of prophylactic does not state the patient is not infected with the disease or an intracellular pathogen that does not affect the central nervous system.
Applicants argument point to the definition of “prophylactic” but Applicants do not acknowledge that “treatment” is also defined in Betbeder and that Betbeder et al disclose the pharmaceutical composition is for use in the prophylactic treatment against an intracellular pathogenic agent in a patient or in the prophylactic treatment of a disease or infection caused by an intracellular pathogenic agent (column 2 lines 18-23). Since Betbeder discloses “prophylactic treatment”, the definition of “treatment” should be considered along with the definition of “prophylactic”.
The definition of “vaccine” as pointed out by Betbeder et al to mean “a product able to prevent infection caused by an intracellular pathogenic agent upon future exposure thereto” and example where the composition is used to prevent infection does not teach away from the clear teachings of Betbeder et al to have used the same composition for “prophylactic treatment”. Betbeder et al discloses a “vaccine” and also discloses a “prophylactic treatment”. Betbeder et al discloses both treatment and prevention.
Contrary to Applicants argument, Betbeder clearly and unequivocally disclose the step of administering to the patient infected with a disease or an intracellular pathogen the disclosed pharmaceutical composition. The embodiment of “treatment” in Betbeder et al disclose (and is not limited to) “if the pathogenic agent may be present in several organs of the patient's body, a decrease of the amount of pathogenic agent or a modification of the pathogenic agent in at least one organ is considered as a treatment effect.”
Betbeder et al defines “patient” (col. 4 lines 62-65) as “a warm-blooded animal such as a mammal which is afflicted with or has the potential to be afflicted with one or more disease and conditions described herein”.
Thus, the definition of “treatment” and “patient” by Betbeder et al expressly or inherently teaches each that the patient is infected with the disease or the intracellular pathogen.
Claim 18: Betbeder et al disclose the protein antigen is from Leishmania spp. See column 4 lines 40-55 and column 4 lines 13-27 particularly line 24.
Betbeder et al does not disclose the Leishmania spp is Leishmania infantum.
Doroud et al disclose that nanoparticulate delivery systems can be used to induce an appropriate immune responses against leishmaniasis. See abstract. Doroud et al disclose the inadequate immunogenicity of Leishmania subcellular antigens might be improved through apply delivery systems in the form of nanocarrier which could protect antigenic proteins or DNA from rapid degradation. See p. 81 under key issues.
Doroud et al disclose that Leishmania infantum causes leishmaniasis particularly visceral leishmaniasis and can also induce cutaneous lesions. See under “what is Leishmania and leishmaniasis” from page 69-70, particular p. 70 column 2 paragraph 4 and entirety of Doroud et al.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date to have used the nanoparticle delivery system of Betbeder et al to deliver a protein antigen from Leishmania infantum, thus resulting in the instant invention with a reasonable expectation of success.
The motivation to do so is that Betbeder et al disclose at least one cationic nanoparticle can be used to deliver protein antigen from Leishmania and Doroud et al disclose that nanoparticulate delivery systems can be used to induce an appropriate immune responses against leishmaniasis caused by Leishmania infantum, and therefore delivering Leishmania infantum antigens using the nanoparticle of Betbeder et al would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date. Moreover, Doroud et al disclose that the immunogenicity of Leishmania subcellular antigens might be improved by delivery via a nanocarrier which could also protect antigenic proteins from rapid degradation. Furthermore, Betbeder et al states that the therapeutic vaccine is a Leishmania antigen and thus using a Leishmania infantum pathogen as one of ordinary skill in the art would have been motivated to treat a L. infantum infection as Doroud et al disclose that L. infantum causes visceral leishmaniasis and they can also induce cutaneous lesions in infected patients.
Response to Applicants’ Argument
14. Applicant argues that Betbeder does not teach or suggest a method of amended claim 17 comprising: “administering to the patient infected with the disease or the pathogen”. Applicants state that Doroud does not cure the deficiencies of Betbeder et al.
15. Applicants argument has been considered but is not found persuasive. Applicants arguments regarding Betbeder have been addressed above and Betbeder disclose embodiments where the patient is afflicted with one or more diseases and conditions described herein and that the patient is infected with a disease or an intracellular pathogen.
The combination of Betbeder and Doroud teach or suggest administering to the patient infected with the disease or pathogen as set forth in the rejection.
For these reasons, the rejection is maintained.
New Claim Rejection Based on Amendment
16. Claim(s) 17, 20, 22, 23, 24, 25 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Roger et al. WO 0234239 05-02-2002 in view of Betbeder et al. US 9,731,005 8/15/17 cited in IDS.
Roger et al teaches a method of treating a patient infected with a disease or an intracellular pathogen that does not affect the central nervous system; comprising
administering to the patient infected with the disease or the pathogen (“More particularly, the invention relates to the preparation of a therapeutic vaccine composition for combating malignant cells or cells infected with pathogenic or infectious agents” - see under “description”)
a therapeutically effective amount of a vaccine composition (“therapeutic vaccine composition”) comprising at least one cationic nanoparticle (“BVSMs (i.e. the nanoparticles) are formed from a crosslinked hydrophilic polymer, preferably polysaccharides, in the form of nanoparticulate gel and the polymer can optionally carry positive ionic ligands, BVSM said cationic, or negative, BVSM said anionic. This charged or uncharged polymer is optionally covered with a layer of amphiphilic compounds, preferably phospholipids.”) including a non-liquid (solid) hydrophilic core consisting of a matrix of polysaccharides or oligosaccharides naturally or chemically cross-linked which can be modified by various ionic groups,
wherein the core is layered with phospholipid (“BVSMs (i.e. the nanoparticles) are formed from a crosslinked hydrophilic polymer, preferably polysaccharides, in the form of nanoparticulate gel and the polymer can optionally carry positive ionic ligands, BVSM said cationic, or negative, BVSM said anionic. This charged or uncharged polymer is optionally covered with a layer of amphiphilic compounds, preferably phospholipids.”)’
and the core is loaded with antigen (the invention concerns the use of particles having a size ranging between 20 and 200 nm comprising a non-liquid hydrophilic core consisting of a matrix of polysaccharides or oligosaccharides naturally or chemically crosslinked, associated with identical or different antigens)
Rogers et al disclose the matrix of polysaccharides are chosen from dextran or starch and the core is loaded with phospholipid.
Roger et al disclose the antigens are specific for the pathology or pathologies for which a cytotoxic cellular immune response TCD8 is sought. Thus, the therapeutic vaccine composition according to the invention can be useful in methods for preventing and / or treating chronic infections of viral origin, such as for example intracellular viruses HSV, HIV, hepatitis B and C, HPV, EBV and intracellular protozoa, as in the case of malaria. Roger et al disclose the therapeutic vaccine composition according to the invention is also useful for treating tumors, in the case of cancers (melanoma, breast, colon, ovarian cancer etc.).
Thus, Rogers et al disclose that the protein antigen specific to the pathogen or the disease is a tumor antigen or a viral antigen from an intracellular virus or an intracellular protozoan.
Rogers et al does not disclose the cationic nanoparticle of the instant claims including a porous solid cationic polysaccharide loaded with anionic phospholipid and protein antigen specific to the pathogen or the disease.
Betbeder et al disclose the use of a cationic nanoparticle including a porous solid cationic polysaccharide core loaded with an anionic phospholipid for the delivery of a protein antigen specific to a pathogen or disease. See column 2 lines 9-23.
Claim 20: Betbeder disclose that the porous solid cationic polysaccharide core is crosslinked and may be obtained by the reaction between a polysaccharide chosen from among starch, dextran, dextrin, and maltodextrin, derivatized with cationic ligands such as quaternary ammonium salts. Primary, secondary and tertiary amines may also be used. More particularly, the cationic polysaccharide can be obtained from the reaction between maltodextrin and glycidyl-trimethylammonium. See column 3 lines 30-37.
Claim 23: Betbeder et al discloses the anionic phospholipid is diacyl phosphatidylglycerol, diacyl phosphatidylserine or diacyl phosphatidylinositol. See column 3 lines 38-42.
Claim 24: Betbeder disclose that the anionic phospholipid is dipalmitoylphosphatidylglycerol (DG). column 3 lines 38-42.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have modified the method of Roger et al by substituting the cationic nanoparticle delivery system of Roger et al with the cationic nanoparticle delivery system of Betbeder et al in order to deliver the protein antigens of Roger wherein the antigens are from a tumor, intracellular virus or intracellular protozoan, thus resulting in the instant invention with a reasonable expectation of success.
The motivation to make the substitution is that both cationic nanoparticles were known to be useful for the delivery of antigens and serve to protect the antigens from degradation (Roger et al disclose the BVSM cationic particle protects biological molecules from degradation) and the results of the substitution would have been predictable – for example protecting the antigen from degradation.
See obviousness rationale-simple substitution of one known element for another to obtain predictable results and some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) and MPEP 2143.
Status of Claims
Claims 17-29 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLUWATOSIN A OGUNBIYI whose telephone number is (571)272-9939. The examiner can normally be reached IFP.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at 5712703497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/OLUWATOSIN A OGUNBIYI/ Primary Examiner, Art Unit 1645
Prosecution Insights