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 .
DETAILED ACTION
Claim Status
Claims 53-57, 68-71 and 82-106 are pending. Claims 90-106 have been added. Claims 58-67, 72-76 and 79-81 have been canceled. Claims 53, 68-71 and 83-89 have been amended. Claims 53-57, 68, 70-71, 82-94 and 96-106 are being examined in this application. In the response to the restriction requirement, Applicants elected sepsis associated with a gram-negative bacterial infection, CER-001, and amino acids 25-267 of SEQ ID NO: 1 of WO 2012/109162. Claims 69 and 95 are withdrawn as being drawn to a nonelected species.
Claim Rejections - 35 USC § 112
The rejection of claim 80 under 35 USC 112(b) is withdrawn in view of the amendments to the claims.
The rejection of claims 79-81 under 35 USC 112(d) is withdrawn in view of the amendments to the claims.
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 rejection has been modified.
Claims 53-57, 68, 70-71, 82-94 and 96-106 are rejected under 35 U.S.C. 103 as being unpatentable over Morin et al. (Front Pharmacol. 2015 Oct 23;6:244) in view of Keyserling et al. (Abstract 15525: CER-001, a Synthetic HDL-Mimetic, Safely Mobilizes Cholesterol in Healthy Dyslipidemic Volunteers, Circulation, Volume 124, Number suppl 21, 22 November 2011), as evidenced by Tardif et al. (Eur Heart J. 2014 Apr 29;35(46):3277-328).
With respect to claims 53 and 89, Morin et al. teach that “[H]igh-density lipoprotein (HDL) is a key component of circulating blood and plays essential roles in regulation of vascular endothelial function and immunity. Clinical data demonstrate that HDL levels drop by 40–70% in septic patients, which is associated with a poor prognosis. Experimental studies using Apolipoprotein A-I (ApoAI) null mice showed that HDL deficient mice are susceptible to septic death, and overexpressing ApoAI in mice to increase HDL levels protects against septic death. These clinical and animal studies support our hypothesis that a decrease in HDL level is a risk factor for sepsis, and raising circulating HDL levels may provide an efficient therapy for sepsis. In this review, we discuss the roles of HDL in sepsis and summarize the efforts of using synthetic HDL as a potential therapy for sepsis” (abstract).
Morin et al. do not teach using CER-001.
Keyserling et al. teach that CER-001 is a synthetic HDL comprising recombinant ApoA-I (abstract).
The MPEP 2144.06 states that it is obvious to substitute equivalents known for the same purpose.
In the instant case, it would have been obvious to one of ordinary skill in the art to substitute the synthetic HDL of Morin et al. with the synthetic HDL of Keyserling et al. (i.e. CER-001).
One of ordinary skill in the art would have had a reasonable expectation of success because Morin et al. teach using synthetic HDL as a therapy for sepsis.
With respect to claims 54-57, 83-87, 90-93 and 101-105, the MPEP 2144.05 A states that “[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. “[W]here 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The 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.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum dosage and time interval between dosages by normal optimization procedures known in the pharmaceutical art.
With respect to claims 68 and 94, Morin et al. teach that the sepsis is associated with a gram-negative bacterial infection (page 2, right column, last para; Table 1; page 5, left column, 2nd para).
With respect to claims 70-71, 82, 96-97 and 100, Morin et al. teach systemic administration (i.e. IP and IV injection) (Table 1). It is noted that, regardless of the location of the sepsis (e.g. in the urogenital tract, in the abdominal cavity, etc.), the skilled artisan would have been motivated to administer the synthetic HDL of Keyserling et al. (i.e. CER-001) because Morin et al. teach using synthetic HDL as a therapy for sepsis associated with a gram-negative bacterial infection.
With respect to claims 88 and 106, given the teachings of Morin et al. and Keyserling et al., it would have been obvious to treat sepsis by administering CER-001 in individuals who never received, are receiving or had received, a standard care therapy for sepsis.
With respect to claim 89, as evidenced by Tardif et al., CER-001 corresponds to the instantly claimed ApoA-I in lipoprotein complexes (page 3279, left column 4th para).
With respect to claims 98-99, Keyserling et al. teach that CER-001 is a synthetic HDL comprising recombinant ApoA-I (which comprises amino acids 25-267 of SEQ ID NO: 2) (abstract).
Response to Arguments
Applicant’s arguments filed on 1/22/2026 have been fully considered but they are not persuasive.
Applicant argues that “[U]nderlying the rejection is an assumption that all "synthetic HDL" such as CSL-111 described in Morin (which comprises ApoA-I and the neutral lipid soybean phosphatidylcholine) and CER-001 (comprises ApoA-I, the neutral lipid sphingomyelin, and the negatively charged lipid DPPG) are interchangeable. Such an assumption is unsupported by evidence in the art. See, e.g., Kalayci et al., 2022 Curr Atherosclero Rep. 24(7):585-597,2 noting in the Abstract that "CER-001 reduce[s] lecithincholesterol acyltransferase (LCAT) activity, potentially impairing the function of HDL in reverse cholesterol transport," while "[i]n contrast to these agents [ApoA-I Milano and CER-001], CSL112, a particle formulated using human plasma apoA-I and phosphatidylcholine, increases LCAT activity and does not lead to the malfunction of endogenous apoA-I." Thus, MPEP 2144.06 does not support the rejection. Second, the Office Action cites Keyserling for its disclosure relating to CER-001, but does not account for later publications relating to CER-001 that would have dissuaded the skilled person from selecting CER-001 as a therapeutic for the treatment of sepsis. Specifically, Keyserling suggests that CER-001 is "a potential therapy for patients with atherosclerotic disease" (Keyserling, abstract) but a subsequent study found no benefit of CER-001 on atherosclerosis. See, Zheng et al., 2020, Atherosclerosis 311:13-19.3 At the time of Applicant's filing, there was simply no indication in the art that CER-001 would be of any use for treating sepsis, and nothing in the cited references that would have motivated the skilled person to even try to use CER-001 in treating sepsis, especially given the observed lack of efficacy for CER- 001 in atherosclerosis, the indication for which CER-001 was initially developed. Third, the use of CER-001 as claimed meets a long-felt but unsolved need, specifically provision of treatments for sepsis. As noted in the background section of the subject application, sepsis is life-threatening due to inadequate treatment options. Morin was published in 2015 and reviews studies going back to the 1990s, and yet no synthetic HDL has been approved for the treatment of sepsis in all of this time. If the skilled person would have been motivated to use a synthetic HDL and in particular CER-001 to treat sepsis, and with a reasonable expectation of success, why was there no progress for so long? To Applicant's knowledge, Applicant is the first to show positive results in human subjects having sepsis (the human subjects mentioned in Morin were healthy subjects administered CSL111, the predecessor of CSL112).
Applicant’s arguments are not persuasive.
First of all, it is noted that the reference of Zheng et al. was published on August 29, 2020 (after the filing of the instant application). Therefore, applicant’s arguments regarding the teachings of Zheng et al. are moot.
Second, although Morin et al. do not specifically teach using CER-001,Keyserling et al. teach that CER-001 is a synthetic HDL comprising recombinant ApoA-I (abstract).
Therefore, since it is obvious to substitute equivalents known for the same purpose, it would have been obvious to one of ordinary skill in the art to substitute the synthetic HDL of Morin et al. with the synthetic HDL of Keyserling et al. (i.e. CER-001) (see MPEP 2144.06).
The skilled artisan would have had a reasonable expectation of success because Morin et al. teach using synthetic HDL as a therapy for sepsis.
For the reasons stated above the rejection is maintained.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658