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 .
Claim Status
Applicants’ amendments and arguments and affidavit filed 3/30/26 are acknowledged. Any objection or rejection from the 10/7/25 office action that is not addressed below is withdrawn based on the amendments.
Claims 2-6, 16-30, 32-60 and 62-72 have been cancelled.
Claims 1, 7-15, 31, 61 and 73 are being examined.
Priority
The priority information is found in the filing receipt dated 3/21/24.
Claim Rejections - 35 USC § 112
This 112 rejection is a new rejection necessitated by amendment specifically the amendment of claim 1 to recite ‘by intravenous infusion’.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 11 is rejected 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.
Claim 1 as amended refers to administering the rHDL ‘by intravenous infusion’. Claim 11 recites ‘rHDL formulation is intravenously (IV) infused’. Thus, claim 11 is not further limiting because it recites information that is already required in claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
Claims were previously rejected under 35 USC 103 based on the references cited below. Since the claims have been amended, an updated rejection appears below.
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, 7-15, 31, 61 and 73 is/are rejected under 35 U.S.C. 103 as being unpatentable over either CSL Behring (reference A27 of IDS 3/15/24; ‘CSL Behring’) or Clinical Trials Entry (Clinical trials entry for NCT02108262 retrieved from https://clinicaltrials.gov/ct2/history/NCT02108262?V_38=View on 7/30/20, 34 pages; ‘Clinical Trials’; reference A13 of IDS 3/15/24) in view of Tricoci et al. (cite A83 of IDS 3/15/24; ‘Tricoci’) in view of Vucica et al. (US 2014/0221272; ‘Vucica’; cited with IDS 3/15/24) in view of Stevens (cite A76 of IDS 3/15/24; ‘Stevens’).
The IDS citation lists the publication date of CSL Behring as April 2014. Further, Clinical Trials refers to the same study and relates to the version of November 9 2015.
The IDS citation lists the publication date of Tricoci as 2015. The pubmed entry (Pubmed entry for Tricoci et al. retrieved from https://pubmed.ncbi.nlm.nih.gov/26307570/ on 8/5/20, 3 pages; cite A84 of IDS 3/15/24) states that the article was published online August 20 2015.
CSL Behring teach subjects with acute myocardial infarction in the last week (page 6). CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
Neither CSL Behring or Clinical Trials teach the specific amount of claim 12, further comprising additional agents as in claim 61, sodium cholate as in claim 31 or patients with moderate renal impairment (compare connecting paragraph on pages 18-19 of the instant specification).
Tricoci teach CSL112 formulations and administrations thereof (page 1). Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph). Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph).
Vucica teach Apo A-1 compositions with phosphatidylcholine and sodium cholate (section 0003). Vucica teach the inclusion of sucrose (section 0004) but recognizes that high sugar concentrations can cause or exacerbate renal problems (sections 0004-0008). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034). Vucica teach various concentration of the apolipoprotein (section 0023). Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Vucica recognizes rHDL formulations for various applications (section 0038). Vucica teach various concentrations and amounts of the apolipoprotein (sections 0023 and 0040) and specifically recite 6g (section 0040). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034 and claim 76). Vucica teach phosphatidylcholine as a lipid (sections 0003, 0027, 0034-0035 and claim 74). Vucica teach a molar ratio of apolipoprotein to lipid of 1:50 (section 0019).Vucica recognize stabilizers specifically at 4.6 to 4.8% (w/w) (section 0010) where the stabilizer is sucrose (sections 0014 and 0034 and claims 51 and 56). Vucica teach a pH range of 6 to 8 (section 0029).
Stevens teach that accurate estimation of glomerular filtration rate is important for the detection of chronic kidney disease (page 486). Stevens teach that levels of eGFR can be categorized into ranges for staging the severity including 30-59 ml/min/1.73m2 (page 487 2nd column 3rd paragraph). Stevens teach that GFR estimates based on serum creatine will remain the mainstay of clinical assessment of kidney function for the foreseeable future (pages 490-492 connecting paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of CSL Behring/Clinical Trials because they specifically suggest administering to subjects with acute myocardial infarction. Since Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5) one would have been motivated to administer such agents based on the nature of the problem to be solved. Since CSL Behring/Clinical Trials specifically teach compositions comprising CSL112 one would have been motivated to use the specific components (including sodium cholate) and concentrations taught by Vucica because Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Since Tricoci specifically administers to those with moderate renal insufficiency and teach that there was no pattern of adverse effects with moderate renal insufficiency one would have been motivated to administer to subjects with moderate renal insufficiency. Since Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph) one would have been motivated to administer to such patients. Since Vucica recognizes rHDL formulations for various applications (section 0038) one would have been motivated to administer for such applications. Since Stevens teach ways to assay the severity of kidney problems one would have been motivated to assess the patients as taught by Stevens. One would have had a reasonable expectation of success since Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph). Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph). Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2).
In relation to the subjects as recited in claim 1, CSL Behring teach subjects with acute myocardial infarction in the last week (page 6). Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Since Tricoci specifically administers to those with moderate renal insufficiency and teach that there was no pattern of adverse effects with moderate renal insufficiency one would have been motivated to administer to subjects with moderate renal insufficiency.
In relation to the formulation recited in claim 1, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph). Tricoci teach CSL112 comprises ApoA-1, phosphatidylcholine and sucrose and a specific ratio of phosphatidylcholine to apoA-I in CSL112 (page 2 last paragraph of column 1). Vucica teach Apo A-1 compositions with phosphatidylcholine and sodium cholate (section 0003). Vucica teach various concentrations and amounts of the apolipoprotein (sections 0023 and 0040) and specifically recite 6g (section 0040). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034 and claim 76). Vucica teach phosphatidylcholine as a lipid (sections 0003, 0027, 0034-0035 and claim 74). Vucica teach a molar ratio of apolipoprotein to lipid of 1:50 (section 0019).Vucica recognize stabilizers specifically at 4.6 to 4.8% (w/w) (section 0010) where the stabilizer is sucrose (sections 0014 and 0034 and claims 51 and 56). Vucica teach a pH range of 6 to 8 (section 0029).
In relation to the administration of claim 1, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
In relation to the increasing CEC in claim 1 line 1, Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2).
In relation to claims 7-8, Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2). The references teach the same agent as claimed so such agent would function as claimed (MPEP 2112.01 II).
In relations to claims 9-10, CSL Behring teach subjects with acute myocardial infarction in the last week (page 6) and Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8) so one would have been motivated to administer over such time frame.
In relation to claim 11, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
In relation to claims 11-12, Vucica teach various concentration of the apolipoprotein (section 0023).
In relation to claims 13-15 and 73, such claims do not require any additional administrations. The references teach the same agent as claimed so such agent would function as claimed. Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph). Tricoci teach that the majority of subjects has creatinine increase of 1 to 1.5x baseline (Table 4).
In relation to the formulations recited in claim 31, Vucica teach the inclusion of sodium cholate at specific amounts (claim 76).
In relation to claim 61, Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5).
Response to Arguments - 103
Applicant's arguments and affidavit filed 3/30/26 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants argue via a declaration that the FDA raised concerns about the safety of CSL112, MPEP 2107.03 recognizes that “The Office must confine its review of patent applications to the statutory requirements of the patent law. Other agencies of the government have been assigned the responsibility of ensuring conformance to standards established by statute for the advertisement, use, sale or distribution of drugs. The FDA pursues a two-prong test to provide approval for testing. Under that test, a sponsor must show that the investigation does not pose an unreasonable and significant risk of illness or injury and that there is an acceptable rationale for the study. As a review matter, there must be a rationale for believing that the compound could be effective. If the use reviewed by the FDA is not set forth in the specification, FDA review may not satisfy 35 U. S. C. 101. However, if the reviewed use is one set forth in the specification, Office personnel must be extremely hesitant to challenge utility. In such a situation, experts at the FDA have assessed the rationale for the drug or research study upon which an asserted utility is based and found it satisfactory. Thus, in challenging utility, Office personnel must be able to carry their burden that there is no sound rationale for the asserted utility even though experts designated by Congress to decide the issue have come to an opposite conclusion. "FDA approval, however, is not a prerequisite for finding a compound useful within the meaning of the patent laws." In re Brana, 51 F.3d 1560, 34 USPQ2d 1436 (Fed. Cir. 1995) (citing Scott v. Finney, 34 F.3d 1058, 1063, 32 USPQ2d 1115, 1120 (Fed. Cir. 1994)).”
Further, MPEP 2164.08 recites “See also United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1370, 2023 USPQ2d 862 (Fed. Cir. 2023) (the court found that the claims directed to administration of treprostinil to treat all five types of pulmonary hypertension, which were construed to not require safety and efficacy, were adequately enabled by the specification which described administration, concentrations and dosages as well as an open label study despite potential safety concerns associated with one type of pulmonary hypotension. The record included evidence that "a skilled artisan would understand that the claimed administration of treprostinil would vasodilate the pulmonary vasculature, improve hemodynamics, and in this way for a single dose, treat a patient’s elevated pulmonary blood pressure independent of the type (i.e., group) of pulmonary hypertension patient.").”.
In the instant case, claim 1 does not even recite treatment, merely administering. Claim 1 does refer to increasing cholesterol efflux. Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2).
United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1370, 2023 USPQ2d 862 (Fed. Cir. 2023) specifically recites:
“Absent incorporation of safety and efficacy requirements in the claims, Liquidia’s argument concerning the safety and efficacy of treating Group 2 PH patients is not before us. Questions of safety and efficacy in patent law have long fallen under the purview of the FDA. In re Brana,
51 F.3d 1560, 1567 (Fed. Cir. 1995) (noting that “the requirements under the law for obtaining a patent” are different from “the requirements for obtaining government approval to market a particular drug for human consumption”); Scott v. Finney, 34 F.3d 1058, 1063 (Fed. Cir. 1994)
(“Testing for the full safety and effectiveness . . . is more properly left to the [FDA]. Title 35 does not demand that such human testing occur within the confines of Patent and Trademark Office (PTO) proceedings.”); In re Anthony, 414 F.2d 1383, 1395 (CCPA 1969) (“Congress has given the responsibility to the FDA, not to the Patent Office, to determine in the first instance whether drugs are sufficiently safe for use that they can be introduced in the commercial market . . . .”). We decline to insert the FDA’s responsibilities into claims by importing requirements where they do not recite such limitations.”, and further recites
“Again, because safety and efficacy are not recited in the claims, we need not deal with Liquidia’s arguments. Disease- specific treatment requirements are matters for the FDA and medical practitioners. They are best suited to make these determinations because practitioners are informed by the findings of the regulatory agency to avoid treatment of patients who will not properly respond. And every claim to a method of treatment of an ailment has refinements. That is, for any given method of treatment claim, there may be a subset of patients who would not benefit from or should not take the claimed treatment.”
Although applicants argue including via the declaration that one of the references alone does not teach a subject with moderate renal impairment, the instant rejection is a multiple reference 103 rejection. As such, any single reference does not necessarily anticipate the claims. Further, the exclusion of a particular patient from a clinical trial is not necessarily a teaching away because there can be many reasons for excluding a particular patient from a clinical trial. In the instant case, Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Since Tricoci specifically administers to those with moderate renal insufficiency and teach that there was no pattern of adverse effects with moderate renal insufficiency one would have been motivated to administer to subjects with moderate renal insufficiency.
Although applicants argue including via a declaration about safety and efficacy based on Vucica, here as in United Therapeutics Corp. v Liquidia Techs., Inc “We decline to insert the FDA’s responsibilities into claims by importing requirements where they do not recite such limitations”. Claim 1 does not even recite treatment, merely administering. Claim 1 does refer to increasing cholesterol efflux. Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2).
Although applicants argue including via a declaration about safety and efficacy based on Tricoci, here as in United Therapeutics Corp. v Liquidia Techs., Inc “We decline to insert the FDA’s responsibilities into claims by importing requirements where they do not recite such limitations”. Claim 1 does not even recite treatment, merely administering. Claim 1 does refer to increasing cholesterol efflux. Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2).
Although applicants argue about the teachings of Tricoci and that the desire to treat a patient population does not amount to a suggestion or expectation that a given treatment would be safe and effective, Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2). Tricoci states that adverse effects were nonserious and mild (‘Methods and Results’ on page 1). Vucica teach that formulations show good stability and low renal toxicity (section 0010). MPEP 2143.02 recognizes that obviousness does not require absolute predictability. Further, MPEP 2107.03 IV recognizes that “Before a drug can enter human clinical trials, the sponsor, often the applicant, must provide a convincing rationale to those especially skilled in the art (e.g., the Food and Drug Administration (FDA)) that the investigation may be successful. Such a rationale would provide a basis for the sponsor’s expectation that the investigation may be successful. In order to determine a protocol for phase I testing, the first phase of clinical investigation, some credible rationale of how the drug might be effective or could be effective would be necessary. Thus, as a general rule, if an applicant has initiated human clinical trials for a therapeutic product or process, Office personnel should presume that the applicant has established that the subject matter of that trial is reasonably predictive of having the asserted therapeutic utility.” In the instant case, CSL Behring expressly teach that 1267 participants are enrolled (page 3) for the phase 2b study (page 1). Clinical Trials entry also teach enrollment of 1200 (anticipated) (page 5) for the phase 2b study (page 1). Vucica teach Apo A-1 compositions with phosphatidylcholine and sodium cholate (section 0003). Vucica teach the inclusion of sucrose (section 0004) but recognizes that high sugar concentrations can cause or exacerbate renal problems (sections 0004-0008). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034). Vucica recognize stabilizers specifically at 4.6 to 4.8% (w/w) (section 0010) where the stabilizer is sucrose (sections 0014 and 0034 and claims 51 and 56). Vucica teach that such formulations show good stability and low renal toxicity (section 0010).
Although applicants argue including via a declaration that the FDA raised concerns about the safety of CSL112 and suggested more tests, MPEP 2107.03 recognizes that “The Office must confine its review of patent applications to the statutory requirements of the patent law. Other agencies of the government have been assigned the responsibility of ensuring conformance to standards established by statute for the advertisement, use, sale or distribution of drugs. The FDA pursues a two-prong test to provide approval for testing. Under that test, a sponsor must show that the investigation does not pose an unreasonable and significant risk of illness or injury and that there is an acceptable rationale for the study.”. MPEP 2143.02 recognizes that obviousness does not conclusive proof of efficacy.
Although applicants argue including via a declaration about the teachings of Gibson, it is first noted that Gibson is not prior art. Gibson refers to CSL112 as being safe and not associated with either hepatotoxicity or renal toxicity (page 82 first complete paragraph). Further, the statement related to a ‘lack of dedicated randomized trials’ in and of itself does not discredit the rejection. MPEP 2144 IV recognizes that the motivation does not have to be same as the inventor’s motivation. There is no requirement that the skilled artisan is limited to clinical trials designed to identify any safety issues.
Further, MPEP 716.01(c) states that with respect to testimony that the examiner must consider: “the nature of the matter sought to be established, the strength of any opposing evidence, the interest of the expert in the outcome of the case, and the presence or absence of factual support for the expert’s opinion”. In the instant case it appears that the nature of the matter sought is to overcome the 103 rejection. With respect to the strength of the opposing evidence, the teachings of references are discussed in detail above. Further, the different standards for FDA requirements are set forth in detail above. With respect to interest of the expert, the affidavit is signed by someone who works for the applicant and who presumably has a vested interest in the outcome of the case. With respect to the presence or absence of factual support, applicants primarily rely on FDA standards and safety concerns. However, claim 1 does not relate to safety nor is claim 1 being examined by FDA standards.
In summary the declaration under 37 CFR 1.132 filed 3/30/26 is insufficient to overcome the rejection of claims as set forth above because: MPEP 2143.02 recognizes that obviousness does not require absolute predictability. Tricoci recognizes that patients with mild renal insufficiency as being included in the administration group (pages 2-3 connecting paragraph) and that there was no pattern of adverse effects with mild or moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Vucica teach that such formulations show good stability and low renal toxicity (section 0010). In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Double Patenting
Claims were previously rejected under double patenting. Since the claims have been amended, updated rejections appear below.
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, 7-15, 31, 61 and 73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 8,999,920 (920; cited with IDS 3/15/24) in view of CSL Behring (reference A27 of IDS 3/15/24; ‘CSL Behring’) or Clinical Trials Entry (Clinical trials entry for NCT02108262 retrieved from https://clinicaltrials.gov/ct2/history/NCT02108262?V_38=View on 7/30/20, 34 pages; ‘Clinical Trials’; reference A13 of IDS 3/15/24) in view of Tricoci et al. (cite A83 of IDS 3/15/24; ‘Tricoci’) in view of Vucica et al. (US 2014/0221272; ‘Vucica’; as cited with IDS 3/15/24) in view of Stevens (cite A76 of IDS 3/15/24; ‘Stevens’).
920 recites treating myocardial infarction (claim 11) by administering a composition comprising an apolipoprotein (claims 1-10).
920 does not specifically teach treating within 7 days of an acute MI event as in claim 1 nor does 920 specifically teach treating those with moderate renal impairment.
The IDS citation lists the publication date of CSL Behring as April 2014. Further, Clinical Trials refers to the same study and relates to the version of November 9 2015.
The IDS citation lists the publication date of Tricoci as 2015. The pubmed entry (Pubmed entry for Tricoci et al. retrieved from https://pubmed.ncbi.nlm.nih.gov/26307570/ on 8/5/20, 3 pages; cite 84 of IDS 3/15/24) states that the article was published online August 20 2015.
CSL Behring teach subjects with acute myocardial infarction in the last week (page 6). CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
Tricoci teach CSL112 formulations and administrations thereof (page 1). Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph). Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph).
Vucica teach Apo A-1 compositions with phosphatidylcholine and sodium cholate (section 0003). Vucica teach the inclusion of sucrose (section 0004) but recognizes that high sugar concentrations can cause or exacerbate renal problems (sections 0004-0008). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034). Vucica teach various concentration of the apolipoprotein (section 0023). Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Vucica recognizes rHDL formulations for various applications (section 0038). Vucica teach various concentrations and amounts of the apolipoprotein (sections 0023 and 0040) and specifically recite 6g (section 0040). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034 and claim 76). Vucica teach phosphatidylcholine as a lipid (sections 0003, 0027, 0034-0035 and claim 74). Vucica teach a molar ratio of apolipoprotein to lipid of 1:50 (section 0019).Vucica recognize stabilizers specifically at 4.6 to 4.8% (w/w) (section 0010) where the stabilizer is sucrose (sections 0014 and 0034 and claims 51 and 56). Vucica teach a pH range of 6 to 8 (section 0029).
Stevens teach that accurate estimation of glomerular filtration rate is important for the detection of chronic kidney disease (page 486). Stevens teach that levels of eGFR can be categorized into ranges for staging the severity including 30-59 ml/min/1.73m2 (page 487 2nd column 3rd paragraph). Stevens teach that GFR estimates based on serum creatine will remain the mainstay of clinical assessment of kidney function for the foreseeable future (pages 490-492 connecting paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 920 because it specifically suggest administering to subjects with acute myocardial infarction. Since Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5) one would have been motivated to administer such agents based on the nature of the problem to be solved. Since CSL Behring/Clinical Trials specifically teach compositions comprising CSL112 one would have been motivated to use the specific components (including sodium cholate) and concentrations taught by Vucica because Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Since Tricoci specifically administers to those with moderate renal insufficiency and teach that there was no pattern of adverse effects with moderate renal insufficiency one would have been motivated to administer to subjects with moderate renal insufficiency. Since Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph) one would have been motivated to administer to such patients. Since Vucica recognizes rHDL formulations for various applications (section 0038) one would have been motivated to administer for such applications. Since Stevens teach ways to assay the severity of kidney problems one would have been motivated to assess the patients as taught by Stevens. One would have had a reasonable expectation of success since Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Tricoci recognizes that patients with mild renal insufficiency as being including in the administration group (pages 2-3 connecting paragraph) and that there was no pattern of adverse effects with mild or moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph). Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph). Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2).
In relation to the subjects as recited in claim 1, CSL Behring teach subjects with acute myocardial infarction in the last week (page 6). Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Stevens teach that accurate estimation of glomerular filtration rate is important for the detection of chronic kidney disease (page 486). Stevens teach that levels of eGFR can be categorized into ranges for staging the severity including 30-59 ml/min/1.73m2 (page 487 2nd column 3rd paragraph). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Since Tricoci specifically administers to those with moderate renal insufficiency and teach that there was no pattern of adverse effects with moderate renal insufficiency one would have been motivated to administer to subjects with moderate renal insufficiency.
In relation to the formulation recited in claim 1, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph). Tricoci teach CSL112 comprises ApoA-1, phosphatidylcholine and sucrose and a specific ratio of phosphatidylcholine to apoA-I in CSL112 (page 2 last paragraph of column 1). Vucica teach Apo A-1 compositions with phosphatidylcholine and sodium cholate (section 0003). Vucica teach various concentrations and amounts of the apolipoprotein (sections 0023 and 0040) and specifically recite 6g (section 0040). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034 and claim 76). Vucica teach phosphatidylcholine as a lipid (sections 0003, 0027, 0034-0035 and claim 74). Vucica teach a molar ratio of apolipoprotein to lipid of 1:50 (section 0019).Vucica recognize stabilizers specifically at 4.6 to 4.8% (w/w) (section 0010) where the stabilizer is sucrose (sections 0014 and 0034 and claims 51 and 56). Vucica teach a pH range of 6 to 8 (section 0029).
In relation to the administration of claim 1, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
In relation to the increasing CEC in claim 1 line 1, Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2).
In relation to claims 7-8, Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2). The references teach the same agent as claimed so such agent would function as claimed (MPEP 2112.01 II).
In relations to claims 9-10, CSL Behring teach subjects with acute myocardial infarction in the last week (page 6) and Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8) so one would have been motivated to administer over such time frame.
In relation to claim 11, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
In relation to claims 11-12, Vucica teach various concentration of the apolipoprotein (section 0023).
In relation to claims 13-15 and 73, such claims do not require any additional administrations. The references teach the same agent as claimed so such agent would function as claimed. Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph).
In relation to the formulations recited in claim 31, Vucica teach the inclusion of sodium cholate at specific amounts (claim 76).
In relation to claim 61, Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5).
Claims 1, 7-15, 31, 61 and 73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,058,747 (747; cited with IDS 3/15/14) in view of CSL Behring (reference A27 of IDS 3/15/24; ‘CSL Behring’) or Clinical Trials Entry (Clinical trials entry for NCT02108262 retrieved from https://clinicaltrials.gov/ct2/history/NCT02108262?V_38=View on 7/30/20, 34 pages; ‘Clinical Trials’; reference A13 of IDS 3/15/24) in view of Tricoci et al. (cite A83 of IDS 3/15/24; ‘Tricoci’) in view of Vucica et al. (US 2014/0221272; ‘Vucica’; as cited with IDS 3/15/24) in view of Stevens (cite A76 of IDS 3/15/24; ‘Stevens’).
747 recites treating myocardial infarction (claim 20) by administering a composition comprising an apolipoprotein (claims 1-10).
747 does not specifically teach treating within 7 days of an acute MI event as in claim 1 nor does 747 specifically teach treating those with moderate renal impairment.
The IDS citation lists the publication date of CSL Behring as April 2014. Further, Clinical Trials refers to the same study and relates to the version of November 9 2015.
The IDS citation lists the publication date of Tricoci as 2015. The pubmed entry (Pubmed entry for Tricoci et al. retrieved from https://pubmed.ncbi.nlm.nih.gov/26307570/ on 8/5/20, 3 pages; cite 84 of IDS 3/15/24) states that the article was published online August 20 2015.
CSL Behring teach subjects with acute myocardial infarction in the last week (page 6). CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
Tricoci teach CSL112 formulations and administrations thereof (page 1). Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph). Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph).
Vucica teach Apo A-1 compositions with phosphatidylcholine and sodium cholate (section 0003). Vucica teach the inclusion of sucrose (section 0004) but recognizes that high sugar concentrations can cause or exacerbate renal problems (sections 0004-0008). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034). Vucica teach various concentration of the apolipoprotein (section 0023). Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Vucica recognizes rHDL formulations for various applications (section 0038). Vucica teach various concentrations and amounts of the apolipoprotein (sections 0023 and 0040) and specifically recite 6g (section 0040). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034 and claim 76). Vucica teach phosphatidylcholine as a lipid (sections 0003, 0027, 0034-0035 and claim 74). Vucica teach a molar ratio of apolipoprotein to lipid of 1:50 (section 0019). Vucica recognize stabilizers specifically at 4.6 to 4.8% (w/w) (section 0010) where the stabilizer is sucrose (sections 0014 and 0034 and claims 51 and 56). Vucica teach a pH range of 6 to 8 (section 0029).
Stevens teach that accurate estimation of glomerular filtration rate is important for the detection of chronic kidney disease (page 486). Stevens teach that levels of eGFR can be categorized into ranges for staging the severity including 30-59 ml/min/1.73m2 (page 487 2nd column 3rd paragraph). Stevens teach that GFR estimates based on serum creatine will remain the mainstay of clinical assessment of kidney function for the foreseeable future (pages 490-492 connecting paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 747 because it specifically suggest administering to subjects with acute myocardial infarction. Since Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5) one would have been motivated to administer such agents based on the nature of the problem to be solved. Since CSL Behring/Clinical Trials specifically teach compositions comprising CSL112 one would have been motivated to use the specific components (including sodium cholate) and concentrations taught by Vucica because Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Since Tricoci specifically administers to those with moderate renal insufficiency and teach that there was no pattern of adverse effects with moderate renal insufficiency one would have been motivated to administer to subjects with moderate renal insufficiency. Since Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph) one would have been motivated to administer to such patients. Since Vucica recognizes rHDL formulations for various applications (section 0038) one would have been motivated to administer for such applications. Since Stevens teach ways to assay the severity of kidney problems one would have been motivated to assess the patients as taught by Stevens. One would have had a reasonable expectation of success since Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Tricoci recognizes that patients with mild renal insufficiency as being including in the administration group (pages 2-3 connecting paragraph) and that there was no pattern of adverse effects with mild or moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph). Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph). Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2).
In relation to the subjects as recited in claim 1, CSL Behring teach subjects with acute myocardial infarction in the last week (page 6). Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Stevens teach that accurate estimation of glomerular filtration rate is important for the detection of chronic kidney disease (page 486). Stevens teach that levels of eGFR can be categorized into ranges for staging the severity including 30-59 ml/min/1.73m2 (page 487 2nd column 3rd paragraph). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Since Tricoci specifically administers to those with moderate renal insufficiency and teach that there was no pattern of adverse effects with moderate renal insufficiency one would have been motivated to administer to subjects with moderate renal insufficiency.
In relation to the formulation recited in claim 1, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph). Tricoci teach CSL112 comprises ApoA-1, phosphatidylcholine and sucrose and a specific ratio of phosphatidylcholine to apoA-I in CSL112 (page 2 last paragraph of column 1). Vucica teach Apo A-1 compositions with phosphatidylcholine and sodium cholate (section 0003). Vucica teach various concentrations and amounts of the apolipoprotein (sections 0023 and 0040) and specifically recite 6g (section 0040). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034 and claim 76). Vucica teach phosphatidylcholine as a lipid (sections 0003, 0027, 0034-0035 and claim 74). Vucica teach a molar ratio of apolipoprotein to lipid of 1:50 (section 0019). Vucica recognize stabilizers specifically at 4.6 to 4.8% (w/w) (section 0010) where the stabilizer is sucrose (sections 0014 and 0034 and claims 51 and 56). Vucica teach a pH range of 6 to 8 (section 0029).
In relation to the administration of claim 1, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
In relation to the increasing CEC in claim 1 line 1, Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2).
In relation to claims 7-8, Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2). The references teach the same agent as claimed so such agent would function as claimed (MPEP 2112.01 II).
In relations to claims 9-10, CSL Behring teach subjects with acute myocardial infarction in the last week (page 6) and Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8) so one would have been motivated to administer over such time frame.
In relation to claim 11, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
In relation to claims 11-12, Vucica teach various concentration of the apolipoprotein (section 0023).
In relation to claims 13-15 and 73, such claims do not require any additional administrations. The references teach the same agent as claimed so such agent would function as claimed. Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph).
In relation to the formulations recited in claim 31, Vucica teach the inclusion of sodium cholate at specific amounts (claim 76).
In relation to claim 61, Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5).
Claims 1, 7-15, 31, 61 and 73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,723,953 (953) in view of CSL Behring (reference A27 of IDS 3/15/24; ‘CSL Behring’) or Clinical Trials Entry (Clinical trials entry for NCT02108262 retrieved from https://clinicaltrials.gov/ct2/history/NCT02108262?V_38=View on 7/30/20, 34 pages; ‘Clinical Trials’; reference A13 of IDS 3/15/24) in view of Tricoci et al. (cite A83 of IDS 3/15/24; ‘Tricoci’) in view of Vucica et al. (US 2014/0221272; ‘Vucica’; as cited with IDS 3/15/24) in view of Stevens (cite A76 of IDS 3/15/24; ‘Stevens’).
953 recites treating myocardial infarction (claim 2) by administering a composition comprising an apolipoprotein (claim 1).
953 does not specifically teach treating within 7 days of an acute MI event as in claim 1 nor does 953 specifically teach treating those with moderate renal impairment.
The IDS citation lists the publication date of CSL Behring as April 2014. Further, Clinical Trials refers to the same study and relates to the version of November 9 2015.
The IDS citation lists the publication date of Tricoci as 2015. The pubmed entry (Pubmed entry for Tricoci et al. retrieved from https://pubmed.ncbi.nlm.nih.gov/26307570/ on 8/5/20, 3 pages; cite 84 of IDS 3/15/24) states that the article was published online August 20 2015.
CSL Behring teach subjects with acute myocardial infarction in the last week (page 6). CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
Tricoci teach CSL112 formulations and administrations thereof (page 1). Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph). Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph).
Vucica teach Apo A-1 compositions with phosphatidylcholine and sodium cholate (section 0003). Vucica teach the inclusion of sucrose (section 0004) but recognizes that high sugar concentrations can cause or exacerbate renal problems (sections 0004-0008). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034). Vucica teach various concentration of the apolipoprotein (section 0023). Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Vucica recognizes rHDL formulations for various applications (section 0038). Vucica teach various concentrations and amounts of the apolipoprotein (sections 0023 and 0040) and specifically recite 6g (section 0040). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034 and claim 76). Vucica teach phosphatidylcholine as a lipid (sections 0003, 0027, 0034-0035 and claim 74). Vucica teach a molar ratio of apolipoprotein to lipid of 1:50 (section 0019).Vucica recognize stabilizers specifically at 4.6 to 4.8% (w/w) (section 0010) where the stabilizer is sucrose (sections 0014 and 0034 and claims 51 and 56). Vucica teach a pH range of 6 to 8 (section 0029).
Stevens teach that accurate estimation of glomerular filtration rate is important for the detection of chronic kidney disease (page 486). Stevens teach that levels of eGFR can be categorized into ranges for staging the severity including 30-59 ml/min/1.73m2 (page 487 2nd column 3rd paragraph). Stevens teach that GFR estimates based on serum creatine will remain the mainstay of clinical assessment of kidney function for the foreseeable future (pages 490-492 connecting paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 953 because it specifically suggest administering to subjects with acute myocardial infarction. Since Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5) one would have been motivated to administer such agents based on the nature of the problem to be solved. Since CSL Behring/Clinical Trials specifically teach compositions comprising CSL112 one would have been motivated to use the specific components (including sodium cholate) and concentrations taught by Vucica because Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Since Tricoci specifically administers to those with moderate renal insufficiency and teach that there was no pattern of adverse effects with moderate renal insufficiency one would have been motivated to administer to subjects with moderate renal insufficiency. Since Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph) one would have been motivated to administer to such patients. Since Vucica recognizes rHDL formulations for various applications (section 0038) one would have been motivated to administer for such applications. Since Stevens teach ways to assay the severity of kidney problems one would have been motivated to assess the patients as taught by Stevens. One would have had a reasonable expectation of success since Vucica teach formulations (abstract and example 1) with reduced renal toxicity (abstract) and that the cholesterol efflux increased as the sucrose concentration decreased (example 4). Tricoci recognizes that patients with mild renal insufficiency as being including in the administration group (pages 2-3 connecting paragraph) and that there was no pattern of adverse effects with mild or moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci recognize patients who have had a previous myocardial infarction (Table 1 on page 5) but not within the last 30 days (page 3 last paragraph). Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph). Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2).
In relation to the subjects as recited in claim 1, CSL Behring teach subjects with acute myocardial infarction in the last week (page 6). Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8). Vucica teach that the target population for rHDL are often renally impaired (section 0005). Stevens teach that accurate estimation of glomerular filtration rate is important for the detection of chronic kidney disease (page 486). Stevens teach that levels of eGFR can be categorized into ranges for staging the severity including 30-59 ml/min/1.73m2 (page 487 2nd column 3rd paragraph). Tricoci teach that there was no pattern of adverse effects with moderate renal insufficiency as compared to those with normal renal function (page 9 first complete paragraph). Tricoci teach that a creatine clearance (CrCl) of <60 mL/min includes moderate renal disease (page 3 last paragraph). Tricoci reveals that the baseline characteristics included subjects with 42 and 55 mL/min CrCl in the treatment group (Table 1 page 5, baseline CrCl min). Since Tricoci specifically administers to those with moderate renal insufficiency and teach that there was no pattern of adverse effects with moderate renal insufficiency one would have been motivated to administer to subjects with moderate renal insufficiency.
In relation to the formulation recited in claim 1, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph). Tricoci teach CSL112 comprises ApoA-1, phosphatidylcholine and sucrose and a specific ratio of phosphatidylcholine to apoA-I in CSL112 (page 2 last paragraph of column 1). Vucica teach Apo A-1 compositions with phosphatidylcholine and sodium cholate (section 0003). Vucica teach various concentrations and amounts of the apolipoprotein (sections 0023 and 0040) and specifically recite 6g (section 0040). Vucica teach specific formulations with specific amounts of sucrose (section 0010), specific ratios of apolipoprotein to lipid (section 0009), the inclusion of sodium cholate at specific amounts (sections 0021 and 0034 and claim 76). Vucica teach phosphatidylcholine as a lipid (sections 0003, 0027, 0034-0035 and claim 74). Vucica teach a molar ratio of apolipoprotein to lipid of 1:50 (section 0019).Vucica recognize stabilizers specifically at 4.6 to 4.8% (w/w) (section 0010) where the stabilizer is sucrose (sections 0014 and 0034 and claims 51 and 56). Vucica teach a pH range of 6 to 8 (section 0029).
In relation to the administration of claim 1, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
In relation to the increasing CEC in claim 1 line 1, Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2).
In relation to claims 7-8, Tricoci teach CSL112 supports cholesterol efflux (page 2 paragraph connecting columns 1-2). The references teach the same agent as claimed so such agent would function as claimed (MPEP 2112.01 II).
In relations to claims 9-10, CSL Behring teach subjects with acute myocardial infarction in the last week (page 6) and Clinical Trials teach subjects with acute myocardial infarction in the last week (page 8) so one would have been motivated to administer over such time frame.
In relation to claim 11, CSL Behring teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (page 3). Clinical Trials teach that subjects receive CSL112 as an intravenous infusion once weekly for 4 consecutive weeks (pages 5-6 connecting paragraph).
In relation to claims 11-12, Vucica teach various concentration of the apolipoprotein (section 0023).
In relation to claims 13-15 and 73, such claims do not require any additional administrations. The references teach the same agent as claimed so such agent would function as claimed. Tricoci teach that no patient had an increase from baseline ALT (page 9-10 connecting paragraph).
In relation to the formulations recited in claim 31, Vucica teach the inclusion of sodium cholate at specific amounts (claim 76).
In relation to claim 61, Tricoci teach current strategies to treat acute coronary syndromes include antithrombotic agents and statins (page 1 first paragraph after abstract) and teach specific patients taking such medications (Table 1 on page 5).
Response to Arguments – double patenting
Applicant's arguments filed 3/30/36 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants argue that the rationale is parallel to the obviousness analysis, as set forth above the arguments related to that rejection are not found persuasive.
Conclusion
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 RONALD T NIEBAUER whose telephone number is (571)270-3059. The examiner can normally be reached M - F 6:30 - 2:30 EST.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658
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