DETAILED ACTION
Notice of 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 .
Status of the Claims
Claims 1-15 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims.
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.
Claims 3-4, 11 and 13-15 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 3-4 recite a method comprising administering a mixture of empty liposomes including, for example, a liposome consisting of cholesterol and sphingomyelin, “wherein the amount of cholesterol... is about 50% (weight per weight)...”.
The parenthetical recitations of “weight per weight” in claims 3-4 render the claims indefinite because it is unclear whether the parenthetical limitations are part of the claimed invention.
Claims 11 and 13-15 recite a method comprising administering a mixture of empty liposomes in at least 2 doses, “wherein the interval between said first and said second dose is 6 to 96 hours, preferably 12 to 72 hours...” (claim 11), “after start of... antibiotic therapy, preferably IV antibiotic therapy” (claim 13), to reduce a duration of hospitalization by “at least one day, preferably two days...” and son on (claim 15).
The phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention.
Claim 13 and 15 are drawn to the method of claim 1 wherein “said composition is administered... no more than 24h after start of said antibiotic therapy” (claim 13) and “wherein the reduction of duration of stay at the hospital due to said adjunctive treatment is...” (claim 15).
Claim 1 does not provide antecedent basis for the recitations of antibiotic therapy, duration of stay at the hospital, and/or adjunctive treatment in claims 13 and 15.
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.
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.
Claims 1-13 are rejected under 35 U.S.C. 103(a) as being unpatentable over Henry et al (Nat Biotech 33:81-88, 2015) in view of Wilkosz et al (Am J Respir Cell Mol Biol 46:180-187, 2012).
Claims 1-4 are drawn to a method of treating pneumonia in a human comprising administering to said human a composition comprising a mixture of empty liposomes, wherein said mixture of empty liposomes consists of a 1:1 w/w mixture of:
(a) a first empty liposome(s) consisting of cholesterol and sphingomyelin in a 1:1 weight ratio, i.e., a 35:65 molar ratio; and
(b) a second empty liposome(s) consisting of sphingomyelin;
wherein said pneumonia is, e.g., severe pneumonia (more specifically, wherein said pneumonia is caused by Streptococcus pneumoniae (claims 7-8)).
Henry et al – investigating “the efficacy of liposomes as a treatment for severe bacterial disease in mice” utilizing “an invasive pneumococcal pneumonia model” (Page 85, Column 1) – teach that “intranasal administration of 100 mg/kg of a 1:1 mixture of Ch:Sm + Sm-only liposomes” (i.e., “unilamellar cholesterol:sphingomyelin (66 mol/% cholesterol; mean diameter = 130 nm) and sphingomyelin (100%; mean diameter = 90 nm) liposomes... product name CAL02”1 (Page 89, Column 1)) to “[p]neumonic mice, infected intranasally with S. pneunomiae D39” (Page 85, Figure 4(b,c)) resulted in “reductions of bacterial load... in the blood and lungs of mice treated with the liposomal mixture” and that “the levels of TNF-α, a signature pro-inflammatory cytokine associated with pneumococcal infection, were considerably reduced in the liposome-treated mice” (Page 85, Column 1; see also Figure 4b and Figure 4c).
As such, Henry et al teach a method of treating severe pneumonia caused by Streptococcus pneumoniae comprising administering a mixture of empty liposomes as claimed. However, whereas Henry et al carry out the method of treating severe pneumonia in mice, the instant claims are drawn to treating severe pneumonia in a human.
Yet, as taught by Wilkosz et al, the pneumonic mouse model utilized by Henry et al (i.e., mice infected intranasally with S. pneunomiae D39) is a “murine model of pneumonia-associated empyema due to S. pneumoniae” – i.e., a severe, complicated form of pneumonia – which “mimics human disease phenotypically, immunologically, and histologically” (Page 184, Column 2; see also Abstract: the model “closely mimics human disease” and “allows for future assessment of molecular mechanisms involved in the development of empyema [“developing as a complication of pneumonia” (Page 180, Column 2)] and evaluation of potential new therapies”; see also Page 181, Column 1: “a novel in vivo model of S. pneumoniae pleural infection arising from pneumonia that resembles human disease”).
Accordingly, in further view of Wilkosz et al, it would have been prima facie obvious to apply the method of Henry et al for the treatment of severe pneumonia in a human, with a reasonable expectation of success.
As such, claims 1-4 and 7-8 are rejected as prima facie obvious.
Claims 5-6 are drawn to the method of claim 1, wherein the pneumonia is a Community Acquired Pneumonia (CAP) (claim 5), more specifically a severe Community Acquired Pneumonia (sCAP) (claim 6).
As further taught by Wilkosz et al, the pneumonic mouse model utilized by Henry et al (i.e., mice infected intranasally with S. pneunomiae D39) “arises from preceding pneumonia and therefore resembles the common clinical course of community-acquired human empyema” (Page 184, Column 2).
Accordingly, the pneumonic mouse model utilized by Henry et al (i.e., mice infected intranasally with S. pneunomiae D39) entails a severe form of community acquired pneumonia.
As such, claims 5-6 are also rejected as prima facie obvious.
Claims 9-10 are directed to the method of claim 1, wherein said treatment is adjunctive to antibiotic therapy (claim 9), more specifically IV antibiotic therapy (claim 10).
As taught by Henry et al, “[a]ntibiotics are the mainstay of treatment against bacterial infection” and, further investigating “whether the combination of liposomes with [IV penicillin] antibiotic treatment could be beneficial in mouse... S. pneumoniae bacteremia models”, report that “[a] combination of liposomal toxin-sequestration and antibiotic treatment was... most effective against fatal sepsis caused by S. pneumoniae” and “[i]n the course of antibiotic-liposome combination therapy, pneumococcal loads in blood 24 h after infection were considerably reduced as compared to antibiotic alone and the pain score (i.e., signs of disease) of mice that were infected with S. pneumoniae were completely eradicated” (Page 87, Column 1; see also Figure 6(b-d)).
In view of the foregoing, it would have been prima facie obvious to carry out the treatment adjunctive to IV antibiotic therapy. As stated in MPEP 2144.06, “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose… [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846 (CCPA 1980).
As such, claims 9-10 are also rejected as prima facie obvious.
Claim 11 is drawn to the method of claim 1, wherein the composition is administered in at least 2 doses, in a first and in a second dose, wherein the interval between said first dose and said second dose is 6 to 96 hours.
As taught by Henry et al, in a related fatal pneumococcal sepsis mouse model in which mice were injected with “the liposomal mixture... at 6 h or 10 h after infection... [b]ecause the levels of liposomes in blood decreased by 50% 4h after injection, we injected mice with liposomes twice with a 4 h interval to maintain a high level of circulating liposomes” (Page 85, Column 2).
Based on the foregoing, it would have been prima facie obvious to administer the composition in at least 2 doses, in a first and in a second dose. It would have been obvious to do so in an effort to maintain a high level of circulating liposomes. And, in doing so, it would have been prima facie obvious to determine the optimal time between said doses in order to provide a desired level of circulating liposomes. As stated by MPEP 2144.05, “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical” (see also In re Aller (220 F.2d 454 (CCPA): “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…” Indeed, as further discussed by the court, “[s]uch experimentation is no more than the application of the expected skill of the [ordinarily skilled artisan] and failure to perform such experiments would, in our opinion, show a want of the expected skill”; see also In re Peterson, 315 F.3d at 1325 (Fed. Cir. 2005): “[t]he normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages” and “[o]nly if the ‘results of optimizing a variable’ are ‘unexpectedly good’ can a patent be obtained for the claimed critical range” (quoting In re Antonie (559 F.2d 618 (CCPA 1977))).
In the instant case, the levels of circulating liposomes is clearly a result-effective variable. Accordingly, it would have been customary for an artisan of ordinary skill in the art to determine the optimal time between doses in order to provide a desired level of circulating liposomes in order to best achieve the desired results.
As such, claim 11 is also rejected as prima facie obvious.
Claim 12 is drawn to the method of claim 1, wherein said composition is administered in the form of a solution for intravenous administration.
At the outset, as drafted, claim 12 merely defines administration of the composition as a solution. While the solution may be “for intravenous administration”, claim 12 does not require that said solution is, in fact, administered intravenously.
And, as discussed above, Henry et al teach “intranasal administration of 100 mg/kg of a 1:1 mixture of Ch:Sm + Sm-only liposomes” (Page 85, Figure 4(b,c)) which entails a solution that could be administered intravenously (see Page 89, Column 1 describing preparation of liposomes and Page 89, Column 2 describing intranasal and intravenous administration of said liposomes).
As such, claim 12 is also rejected as prima facie obvious.
Claim 13 is drawn to the method of claim 1 (which is understood as claim 9), wherein said composition is administered in at least 2 doses, wherein a first does is administered no more than 24 hours after the start of said antibiotic therapy.
As discussed above, Henry et al teach the “[a]djunct therapy with liposomes” (page 87, Column 1). More specifically, Henry et al teach simultaneous administration of a “combination of liposomes with antibiotic therapy” in two doses “at 10 and 24 h post infection” (Page 87, Column 1).
As such, claim 13 is also rejected as prima facie obvious.
Claims 14-15 are rejected under 35 U.S.C. 103(a) as being unpatentable over Henry et al (Nat Biotech 33:81-88, 2015) in view of Wilkosz et al (Am J Respir Cell Mol Biol 46:180-187, 2012) as applied to claims 1-13 above, in further view of Menendez et al (Eur Respir J 18:151-156, 2001).
Claims 14-15 are drawn to the method of claim 1, wherein said pneumonia requires a stay of said patient at a hospital and wherein said treatment is adjunctive to antibiotic therapy, and wherein said adjunctive treatment reduces the duration of stay at said hospital as compared to a stat at the hospital when no such treatment is effected (claim 14), more specifically wherein the reduction of the duration of stay is at least one day (claim 15).
As discussed above, Henry et al in view of Wilkosz et al teach a method of treating a severe form of community acquired pneumonia caused by Streptococcus pneumoniae in a human patient in need thereof, comprising administering a mixture of empty liposomes as an adjunctive to antibiotic therapy to said patient. However, Henry et al in view of Wilkosz et al do not specifically teach the method wherein the pneumonia requires a stay of said patient at a hospital and wherein said treatment reduces the duration of stay.
Yet, as taught by Menendez et al, “[c]ommunity-acquired pneumonia (CAP) has an estimated incidence of 1-5 per 1,000 of the population, with ~30% of patients admitted to the hospital for treatment” wherein “[g]enerally, patients with bacterial infections stay in hospital for 7-10 days” (Page 151, Column 1).
In view of the foregoing, it would have been prima facie obvious to apply the method of Henry et al in view of Wilkosz et al, comprising administering a mixture of empty liposomes as an adjunctive to antibiotic therapy for treating a human patient suffering from a severe form of community acquired pneumonia caused by Streptococcus pneumoniae, specifically wherein said pneumonia requires hospitalization. It would have been obvious to do so in an effort to treat the approximately 30% of patients suffering from CAP that require hospitalization, as taught by Menendez et al, with a reasonable expectation of success. And, in doing so, it is necessarily the case that said treatment would reduce the duration of hospital stay by at least 1 day.
As such, claims 14-15 are also rejected as prima facie obvious.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,059,496.
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘496 claims are similarly drawn to methods of treating severe pneumonia in a human comprising administering to said human a composition comprising a mixture of empty liposomes, wherein said mixture of empty liposomes consists of a 1:1 w/w mixture of (a) a first empty liposome(s) consisting of cholesterol and sphingomyelin in a 1:1 weight ratio, i.e., a 35:65 molar ratio; and (b) a second empty liposome(s) consisting of sphingomyelin.
Conclusion
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611
1 as indicated by the instant Specification, “the preferred composition of the present invention [is]... named CAL02”