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 .
Claims 1-20 are pending in this application, Claims 1-5, 9, 13-15 and 18 are acknowledged as withdrawn, Claims 6-8, 10, 11, 17, 19 and 20 were examined on their merits.
The objection to the Specification due to the improper use of Trademarks has been withdrawn due to the Applicant’s amendments to the Specification filed 01/15/2026.
The objection to Claim 1 because of minor informalities has been withdrawn due to the Applicant’s amendments to the claims filed 01/15/2026.
The objection to Claims 10 and 20 because of minor informalities has been withdrawn due to the Applicant’s amendments to the claims filed 01/15/2026.
The rejection of Claim 11 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to pre-AIA 35 U.S.C. 112, the Applicant), regards as the invention, has been withdrawn due to the Applicant’s amendments to the claims filed 01/15/2026.
The rejection of Claim 11 under 35 U.S.C. § 112(d) or pre-AIA 35 U.S.C. § 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject
matter of the claim upon which it depends, or for failing to include all the limitations of
the claim upon which it depends, has been withdrawn due to the Applicant’s amendments to the claims filed 01/15/2026.
The rejection of Claims 6, 19 and 20 under 35 U.S.C. § 103 as being unpatentable over Cronemberger-Andrade et al. (2014), cited in the IDS, in view of Ercelen et al. (WO2019/077534 A1), as evidenced by Beckman (2025), has been withdrawn due to the Applicant’s amendments to the claims filed 01/15/2026 removing “emulsion systems.
The rejection of Claim 6-8, 19 and 20 under 35 U.S.C. § 103 as being unpatentable over Cronemberger-Andrade et al. (2014), cited in the IDS, in view of Ercelen et al. (WO2019/077534 A1), as evidenced by Beckman (2025), as applied to Claims 6, 19 and 20, and further in view of Faustino et al. (2020), has been withdrawn due to the Applicant’s amendments to the claims filed 01/15/2026.
The rejection of Claim 6, 10, 11, 19 and 20 under 35 U.S.C. § 103 as being
unpatentable over Cronemberger-Andrade et al. (2014), cited in the IDS, in view of
Ercelen et al. (WO2019/077534 A1), as evidenced by Beckman (2025), as applied to
Claims 6, 19 and 20, and further in view of Taylor et al. (US 2010/0092524 A1), has been withdrawn due to the Applicant’s amendments to the claims filed 01/15/2026.
The rejection of Claim 6, 17, 19 and 20 under 35 U.S.C. § 103 as being unpatentable over Cronemberger-Andrade et al. (2014), cited in the IDS, in view of Ercelen et al. (WO2019/077534 A1), as evidenced by Beckman (2025), as applied to Claims 6, 19 and 20, and further in view of Hong et al. (2008), has been withdrawn due to the Applicant’s amendments to the claims filed 01/15/2026.
Claim Interpretation
Claims 19-20 are being construed as product-by-process limitations consistent
with the MPEP at 2113, I. and II. wherein the product is "isolated extracellular vesicles"
and the process is set forth by the limitations of Claims 19 and 20.
Claim Rejections - 35 USC § 112
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 6-8, 10, 11, 17, 19 and 20 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 6 recites the limitation "the active drug". There is insufficient antecedent basis for this limitation in the claim which only recites “active compound”. Claims 7, 8, 10, 11, 17, 19 and 20 are rejected as being dependent upon rejected Claim 6.
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.
Claim 6, 7, 8, 19 and 20 are newly rejected under 35 U.S.C. § 103 as being unpatentable over Cronemberger-Andrade et al. (2014), cited in the IDS, as evidenced by Beckman (2025), of record, in view of Faustino et al. (2020), of record, and Sato et al. (2016), as necessitated by Applicant’s amendment to the claims filed 01/15/2026.
Cronemberger-Andrade et al. teaches a method comprising infecting
macrophages with Leishmania amazonensis and collecting/isolating exosomes having a diameter of 50-300 nm (Pg. 4, Column 1, Lines 33-35, overlapping the claimed range of less than 220 nm and rendering it prima facie obvious, see MPEP 2144/05, I.) from the culture media by centrifuging at 100,000 g (an "ultracentrifugation" as evidenced by Beckman, Pg. 1, Line 3), thereby forming a "pharmaceutical composition", giving the term its’ broadest reasonable interpretation (Pg. 2, Column 2, Lines 20-41);
the reference suggests the use of EVs in vaccination and immunotherapeutic
procedures and may confer a resistant phenotype to Leishmania infection in vivo and in
vitro (Pg. 9, Column 1, Lines 3-4 and 11-13), and reading on Claims 6 and 19.
With regard to Claims 19 and 20, consistent with the claim interpretation set forth
above, the isolated exosomes/extracellular vesicles of Cronemberger-Andrade et al.
appear to be the same (structurally indistinct) as, or prima facie obvious over the claimed isolated exosomes/extracellular vesicles even if produced by a different process. The burden shifts to Applicant to come forward with evidence establishing an nonobvious difference between the claimed product and the prior art product.
Cronemberger-Andrade et al. does not teach that the pharmaceutical
composition of exosomes comprises a lipid vesicular nano-carrier system, or at least one active compound which is encapsulated within the extracellular vesicles to prevent direct contact of the active compound with a macrophage surface, as now required by Claim 6;
or a composition wherein the active compound/therapeutic
molecule is the anti-parasitic amphotericin B, as required by Claims 7 and 8.
Faustino et al. teaches that Amphotericin B (AmB) remains the gold standard in
the treatment of invasive fungal infections and visceral, cutaneous and mucocutaneous
leishmaniasis (Pg. 1, Abstract and Pg. 2, Lines 42-49 and Pg. 3, Lines 1-2) and
discloses lipid-based formulations of AmB (Pg. 1, Abstract).
Sato et al. teaches that exosomes are small membrane vesicles having a diameter of 50-200 nm (overlapping the claimed size range of less than 220 nm) and a method of preparing a fusion between liposomes (lipid vesicular system) and exosomes which allows for the optimizing of the properties of the exosome surface in order to decrease its’ immunogenicity, increase its’ colloidal stability and improve the half-life of exosomes in blood (Pg. 1, Lines 5-6 and 28-29 and Pg. 2, Lines 1-3) wherein the exosome-liposome fusion method should be useful for loading therapeutic agents (e.g. compounds) into exosomes (thus a “pharmaceutical composition”) (Pg. 6, Lines 29-30).
The therapeutic agents loaded into the exosome-liposome fusion of Sato would be prevented from direct contact with a macrophage surface as the compound is within the exosome-liposome fusion and thus physically separated from macrophages.
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the pharmaceutical composition of isolated
exosomes of Cronemberger-Andrade et al. suggested as a therapeutic for Leishmania infection in vivo and in vitro to modify the exosomes to an exosome-liposome fusion carrier system which prepares loaded/encapsulated therapeutic agents into the exosomes as taught by Sato et al., wherein the exosomes-liposome fusion is loaded with the Leishmaniasis therapeutic agent AmB, as taught by Faustino et al. because this is a suitable form in the art for combining/loading isolated exosomes with a therapeutic compound. Those of ordinary skill in the art would have been motivated to make this modification in order to prepare an anti-Leishmania pharmaceutical composition of exosome-liposome fusion carrier system additionally loaded with an anti-leishmaniasis therapeutic agent, which are both known or suggested in the art as anti-Leishmania treatments. The combination thereof for the same purpose would have been prima facie obvious, see the MPEP at 2144.06, I. Those of ordinary skill in the art would have been additionally motivated to make this modification because Sato teaches that the exosomes-liposomes fusion carrier system has decreased immunogenicity, increased colloidal stability, and improved the half-life in blood.
There would have been a reasonable expectation of success in making this modification because at least the Cronemberger-Andrade et al. and Sato et al. references are drawn to the same field of endeavor, that is, compositions and uses of therapeutic exosomes, and the Cronemberger-Andrade et al. and Faustino et al. references are drawn to the same field of endeavor, that is, anti-Leishmania pharmaceutical compositions.
Claim 6, 7, 8, 10, 11, 19 and 20 are newly rejected under 35 U.S.C. § 103 as being unpatentable over Cronemberger-Andrade et al. (2014), cited in the IDS, as evidenced by Beckman (2025), of record, in view of Faustino et al. (2020), of record, and Sato et al. (2016), as applied to Claims 6, 7, 8, 19 and 20 above, and further in view of Taylor et al. (US 2010/0092524 A1), of record, as necessitated by Applicant’s amendment to the claims filed 01/15/2026.
The teachings of Cronemberger-Andrade et al., Faustino et al. and Sato et al. were discussed above.
None of the above references taught a composition comprising exosomes in combination with at least one of aluminum hydroxide, aluminum phosphate, tocopherol emulsion systems containing 3D-MPL, cholesterol, and CpG oligonucleotide, as required by Claim 10;
or wherein the composition is administered parenterally, as required by Claim 11.
Taylor et al. teaches a pharmaceutical composition comprising exosomes and exogenous polypeptide and one or more adjuvants to enhance the polypeptides immunogenicity, wherein the adjuvants include aluminum hydroxide, aluminum phosphate and oligodeoxyribonucleotide sequences having one or more non-
methylated CpG units (Pg. 6, Paragraph [0062]);
and wherein administration may be, for example, intravenously, intratumorally,
subcutaneously, transdermally, or intraperitoneally (parenteral) (Pg. 10, Paragraph
[0096]).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the pharmaceutical composition of isolated
exosomes-liposome fusion loaded with a the anti-leishmania therapeutic agent AmB of Cronemberger-Andrade et al., Faustino et al. and Sato et al. to administer the composition parenterally and include an adjuvant as taught by Taylor et al. because this would serve to deliver the composition to a subject in need thereof and enhance immunogenicity of the AmB loaded exosome-liposome fusion comprising vaccine/immunotherapeutic of Cronemberger-Andrade, Faustino and Sato. Those of ordinary skill in the art would have been motivated to make this modification in order to provoke an immune response in a subject whom has been parenterally administered the composition as a vaccine/treatment. There would have been a reasonable expectation of success in making this modification because at least the Cronemberger-Andrade et al. and the Taylor et al. references are drawn to the same field of endeavor, that is, compositions and uses of therapeutic exosomes.
Claim 6, 7, 8, 17, 19 and 20 are newly rejected under 35 U.S.C. § 103 as being unpatentable over Cronemberger-Andrade et al. (2014), cited in the IDS, as evidenced by Beckman (2025), of record, in view of Faustino et al. (2020) , of record, and Sato et al. (2016), as applied to Claims 6, 7, 8, 19 and 20 above, and further in view of Hong et al. (2008), of record, as necessitated by Applicant’s amendment to the claims filed 01/15/2026.
The teachings of Cronemberger-Andrade et al., Faustino et al. and Sato et al. were discussed above.
None of the above references taught a composition comprising exosomes obtained from macrophages infected with L. arabica, as required by Claim 17.
Hong et al. teaches that L. amazonensis and L. arabica are both known in the art
(Pg. 2, Lines 1-4) and the life cycle of Leishmania parasites involves infection of
macrophages (Pg. 2, Lines 8-15).
It would have been obvious to those of ordinary skill in the art before the effective
filing date of the claimed invention to modify the pharmaceutical composition of isolated
exosomes from macrophages infected with L. amazonensis, fused with liposomes and loaded with the anti-leishmania therapeutic agent AmB of Cronemberger-Andrade et al., Faustino et al. and Sato et al. to use exosomes obtained from macrophages infected with L. arabica because both species are art-recognized equivalents capable of infecting macrophages. Those of ordinary skill in the art would have been motivated to make this modification based on the availability of pathogens and artisan preference. There would have been a reasonable expectation of success in making this modification because Cronemberger-Andrade et al. teaches the isolation of exosomes from macrophages infected with L. amazonensis and Hong et al. teaches that L. amazonensis and L. arabica are both known in the art and capable of infecting macrophages.
Response to Arguments
Applicant’s arguments, see Remarks, filed 01/15/2026, with respect to the above withdrawn objections/rejection have been fully considered and are persuasive.
Applicant's arguments filed 01/15/2026 have been fully considered but they are not persuasive insofar as they apply to the new rejections above.
The Applicant argues that Cronemberger-Andrade does not disclose isolated exosomes and an additional nano-carrier system and Ercelen teaches isolated exosomes loaded with therapeutic molecules in an emulsion system and not the recited nano-carrier systems (Remarks, Pg. 39, Lines 9-27).
This is not found to be persuasive for the reasoning provided in the new rejections based in part on Sato et al. above.
The Applicant argues that neither Cronemberger-Andrade or Ercelen meet the limitation that the exosomes have a size less than 220 nm (Remarks, Pg. 39, Lines 28-29 and Pg. 40, Lines 1-4).
This is not found to be persuasive for the following reasons, as discussed above, Cronemberger-Andrade et al. teaches a method comprising infecting macrophages with Leishmania amazonensis and collecting/isolating exosomes having a diameter of 50-300 nm (Pg. 4, Column 1, Lines 33-35, overlapping the claimed range of less than 220 nm and rendering it prima facie obvious, see MPEP 2144/05, I.) and Sato et al. teaches that exosomes are small membrane vesicles having a diameter of 50-200 nm (overlapping the claimed range of less than 220 nm) (Pg. 1, Lines 5-6). Thus, both references obviate the claimed exosome size range.
The Applicant argues that neither Cronemberger-Andrade or Ercelen teach or suggest the encapsulation of an active compound to prevent macrophage surface contact as claimed (Remarks, Pg. 40, Lines 5-16).
This is not found to be persuasive for the reasoning provided in the new rejections based in part on Sato et al. above. Sato et al. teaches the exosome-liposome fusion method should be useful for loading therapeutic agents (e.g. compounds) into exosomes (thus a “pharmaceutical composition”) (Pg. 6, Lines 29-30). The therapeutic agents loaded into the exosome-liposome fusion of Sato would thus be prevented from direct contact with a macrophage surface as the therapeutic compound is within the exosome-liposome fusion and thus physically separated from macrophages.
The Applicant argues that the Examiner’s finding of obviousness is conclusory and lacks articulated reasoning with rational underpinning as Cronemberger-Andrade is directed to the immunological effects of EVs release from Leishmania infected macrophages and their potential beneficial effects and not to the loading thereof with drug-loaded emulsions while Ercelen is directed to exosomes loaded with emulsified therapeutic molecules. Applicant concludes that without a specific reason or motivation why the ordinary artisan would modify Cronemberger-Andrade in view of Ercelen (Remarks, Pg. 41, Lines 15-31).
This is not found to be persuasive for the reasoning provided in the new rejections based in part on Sato et al. above.
It would have been obvious to those of ordinary skill in the art to modify the pharmaceutical composition of isolated exosomes of Cronemberger-Andrade et al. to use an exosome-liposome fusion carrier system in the composition which prepares loaded/encapsulated therapeutic agents into the exosomes as taught by Sato et al. because this is a suitable form in the art for combining/loading isolated exosomes with a therapeutic compound. Those of ordinary skill in the art would have been motivated to make this modification in order to prepare a pharmaceutical composition of exosomes-liposomes loaded with a therapeutic agent having decreased immunogenicity, increased colloidal stability, and improved the half-life in blood.
The Applicant argues that Faustino does not provide a reason to load AmB into infected-macrophage exosomes/EVs or suggest why such a modification would be predictable in view of the other cited references. Applicant asserts that the Examiner’s rationale is an impermissible conclusory statement rather than a technically supported rationale (Remarks, Pg. 42, Lines 1-15).
This is not found to be persuasive for the reasoning provided in the new rejections based in part on Sato et al. above.
That is, it would have been obvious to those of ordinary skill in the art to modify the pharmaceutical composition of isolated exosomes-liposome fusion loaded with a generic therapeutic agent of Cronemberger-Andrade et al. and Sato et al. to use AmB as the therapeutic agent as taught by Faustino et al. because Cronemberger-Andrade teaches that exosomes isolated from Leishmania infected macrophages have therapeutic potential in vaccination and immunotherapeutic procedures and may confer a resistant phenotype to Leishmania infection in vivo and in vitro and Faustino teaches another anti-Leishmania treatment. The combination thereof for the same purpose would have been prima facie obvious, see the MPEP at 2144.06, I. Those of ordinary skill in the art would have been motivated to make this modification in order to prepare an anti-Leishmania pharmaceutical composition of Leishmania derived exosomes loaded with AmB and fused with liposomes as both known or suggested in the art as anti-Leishmania treatments.
The Applicant argues that with regard to the rejection in view of Taylor, the Examiner’s rationale is overly generic and does not articulate why the ordinary artisan would have been motivated to apply the teachings of Taylor to Cronemberger-Andrade with a reasonable expectation of success (Remarks, Pg. 42, Lines 16-30 and Pg. 43, Lines 1-2).
This is not found to be persuasive for the reasoning provided in the new rejections based in part on Sato et al. above.
That is, it would have been obvious to those of ordinary skill in the art to modify the pharmaceutical composition of isolated exosomes-liposome fusion loaded with a therapeutic agent of Cronemberger-Andrade et al. and Sato et al. to use AmB as the therapeutic agent as taught by Faustino et al. because Cronemberger-Andrade teaches that exosomes isolated from Leishmania infected macrophages have therapeutic potential in vaccination and immunotherapeutic procedures and may confer a resistant phenotype to Leishmania infection in vivo and in vitro and Faustino teaches another anti-Leishmania treatment. The combination of the two separate anti-leishmania methods/compositions for the same purpose would have been prima facie obvious, see the MPEP at 2144.06, I. Those of ordinary skill in the art would have been motivated to make this modification in order to prepare an anti-Leishmania pharmaceutical composition comprising Leishmania derived exosomes loaded with AmB, which are both known or suggested in the art as anti-Leishmania treatments.
The Applicant argues that the Examiner’s rationale that the ordinary artisan could substitute L. arabica and L. amazonensis is conclusory and lacks a rational, technical underpinning that doing so would be predictable (Remarks, Pg. 43, Lines 3-18).
This is not found to be persuasive for the following reasons, as discussed above, it would have been obvious to those of ordinary skill in the art to modify the pharmaceutical composition of isolated exosomes-liposome fusion loaded with a therapeutic agent of Cronemberger-Andrade et al. and Sato et al. to administer the composition parenterally and include an adjuvant as taught by Taylor et al. because this would serve to deliver the composition to a subject in need thereof and enhance immunogenicity of the exosome-liposome comprising vaccine/immunotherapeutic of Cronemberger-Andrade and Sato. Those of ordinary skill in the art would have been motivated to make this modification in order to provoke an immune response in a subject whom has been parenterally administered the composition as a vaccine/treatment. There would have been a reasonable expectation of success in making this modification because at least the Cronemberger-Andrade et al. and the Taylor et al. references are drawn to the same field of endeavor, that is, compositions and uses of therapeutic exosomes.
The Applicant argues that the Examiner’s rationale for combining Cronemberger-Andrade and Ercelen is impermissible hindsight (Remarks, Pg. 44, Lines 11-27).
In response to Applicant's argument that the Examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning.
But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the Applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this instance, as discussed above, it would have been obvious to those of ordinary skill in the art to modify the pharmaceutical composition of isolated exosomes of Cronemberger-Andrade et al. to use an exosome-liposome fusion carrier system in the composition which prepares loaded/encapsulated therapeutic agents into the exosomes as taught by Sato et al. because this is a suitable form in the art for combining/loading isolated exosomes with a therapeutic compound. Those of ordinary skill in the art would have been motivated to make this modification in order to prepare a pharmaceutical composition of exosomes-liposomes loaded with a therapeutic agent having decreased immunogenicity, increased colloidal stability, and improved the half-life in blood.
The Applicant argues that the Examiner’s finding of obviousness based in part on the teachings of Faustino is impermissible hindsight reconstruction (Remarks, Pg. 45, Lines 2-10).
In response to Applicant's argument that the Examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning.
But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the Applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this instance, as discussed above, it would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the pharmaceutical composition of isolated exosomes-liposome fusion loaded with a therapeutic agent of Cronemberger-Andrade et al. and Sato et al. to use AmB as the therapeutic agent as taught by Faustino et al. because Cronemberger-Andrade teaches that exosomes isolated from Leishmania infected macrophages have therapeutic potential in vaccination and immunotherapeutic procedures and may confer a resistant phenotype to Leishmania infection in vivo and in vitro and Faustino teaches another anti-Leishmania treatment. The combination thereof for the same purpose would have been prima facie obvious, see the MPEP at 2144.06, I.
The Applicant argues that the Examiner’s finding of obviousness based in part on the teachings of Taylor is impermissible hindsight reconstruction (Remarks, Pg. 45, Lines 11-23).
In response to Applicant's argument that the Examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning.
But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the Applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this instance, as discussed above, it would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the pharmaceutical composition of isolated exosomes-liposome fusion loaded with a therapeutic agent of Cronemberger-Andrade et al. and Sato et al. to administer the composition parenterally and include an adjuvant as taught by Taylor et al. because this would serve to deliver the composition to a subject in need thereof and enhance immunogenicity of the exosome-liposome comprising vaccine/immunotherapeutic of Cronemberger-Andrade and Sato.
The Applicant argues that the Examiner’s finding of obviousness based in part on the teachings of Hong is impermissible hindsight reconstruction (Remarks, Pg. 45, Lines 24-29 and Pg. 46, Lines 1-6).
In response to Applicant's argument that the Examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning.
But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the Applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this instance, as discussed above, it would have been obvious to those of ordinary skill in the art to modify the pharmaceutical composition of isolated exosomes from macrophages infected with L. amazonensis, fused with liposomes and loaded with a therapeutic agent of Cronemberger-Andrade et al. and Sato et al. to use exosomes obtained from macrophages infected with L. arabica because both species are art-recognized equivalents capable of infecting macrophages. Thus, the ordinary artisan would recognize that either species could be used to produce the Leishmania infected macrophages from which exosomes are isolated.
The Applicant argues that the inventors have identified and solved a solution to a “previously unknown problem” not meaningfully addressed in the prior art (Remarks, Pg. 47, Lines 1-22).
This is not found to be persuasive for the following reasons, the case law cited by Applicant is based on an unknown adverse interaction between an active agent and a coating which is known, would have made obvious the use of an undercoating. However, since the problem had not been previously known, there would have been no reason to incur additional time and expense to add another layer, even though the addition would have been technologically possible.
This is true because the prior art of record failed to mention any stability problem, despite the acknowledgment during testimony at trial that there was a known theoretical reason that omeprazole might be subject to degradation in the presence of the known coating material.
Applicant likens the rationale to the problem Applicant addressed of direct contact with an anti-protozoan drug with macrophage surfaces during targeted drug delivery driving host cell toxicity and undermining selectivity prompting the inventors to incur additional time/expense and formulation complexity to address the problem (Remarks, Pg. 47, Lines 1-22).
This is not found to be persuasive for the following reasons, the Applicant is not the first to encapsulate/incorporate an active agent/compound/drug into exosomes. In fact, Sato teaches loading therapeutic agents into an exosome-liposome fusion which would be prevented from direct contact with a macrophage surface as the compound is within the exosome-liposome fusion and thus physically separated from macrophages. In response to Applicant's argument that encapsulating an active agent in exosomes avoids direct contact of the active agent with macrophage surfaces during targeted drug delivery thereby reducing host cell toxicity and increasing selectivity, the fact that the inventor has recognized another advantages which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
The Applicant argues that the dependent claims are not suggested by the prior art and do not address the alleged previously unknown problem solved by Applicant and/or are based on impermissible hindsight and conclusory statements (Remarks, Pg. 47, Lines 24-28, Pgs. 48-49 and Pg. 50, Lines 1-8).
This is not found to be persuasive for the reasoning provided in the new rejections based in part on Sato et al. above. In response to Applicant's argument that the Examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the Applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this instance, as discussed above, the ordinary artisan would have found obvious the combination of the cited prior art to arrive at the claimed invention for the logical reasoning provided above. Further, the Applicant is not the first to encapsulate/incorporate an active agent/compound/drug into exosomes. For example, the Sato reference published three years before the effective filing date, teaches loading therapeutic agents into an exosome-liposome fusion which would be prevented from direct contact with a macrophage surface as the compound is within the exosome-liposome fusion and thus physically separated from macrophages.
In response to Applicant's argument that encapsulating an active agent in exosomes avoids direct contact of the active agent with macrophage surfaces during targeted drug delivery thereby reducing host cell toxicity and increasing selectivity, the fact that the inventor has recognized another advantages which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Conclusion
No claims are allowed.
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 PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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, Sharmila G Landau can be reached at (571) 272-0614. 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.
/PAUL C MARTIN/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653