Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims Rejections 35 USC 112 (A)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
While applicants are enable for the lipid-binding protein-based complex,” CER-001, they are no enable for the scope of this complex.
MPEP § 2137 states that "the written description requirement for a genus must be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
For written description, the analysis (a) considers actual reduction to practice, (b) disclosure of drawing or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed and (d) representative number of examples.
actual reduction to practice/(b) disclosure of drawing or structural chemical formulas:
Applicants have only reduced CER-001 to practice and only recite CER-001 as a
fully described example of a “lipid-binding protein-based complex.” The claimed invention is based on applicants’ finding that subjects treated with a high dose of the lipid binding protein-based complex CER-001 as described in Example 2 showed an unexpectedly rapid improvement in biomarkers of inflammation, leukocytosis, and endothelial dysfunction [see specification 0003]. There is no limiting definition of lipid binding protein-based complex, which has an extremely broad description in the specification as including an apomer, a cargomer, an HDL based complex, or an HDL mimetic based complex, but the specification only states that “in specific embodiments, the lipid binding protein-based complex is CER-0001.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties
The specification states that the exemplary features of lipid binding protein-based complexes are that they “can be used in the methods and compositions of the disclosure” and they fall within the extremely variant description of lipids, as discussed in section 5.1. This secretin primarily describes the method of use for the claimed product in lipid binding, and the types of lipids, but does not adequately discuss the complex or the required structural features of the lipid binding protein-based complex. Without a definition of this complex, no feature, aside from being “peptide-based” are claimed.
While there are various similar embodiments provides in 0053-0062 of the specification, none are reduced to practice, and all of them require similar features to the CER-001 reduced to practice, such as 2-4 ApoA-I equivalents, 2 molecules of charged phospholipid, 50-80 molecules of lecithin and 20 molecules of sphingolipid. The only example provided and reduced to practice is CER-001, which is a is a negatively-charged lipoprotein particle that contains human recombinant apoA-I, the natural HDL protein, and two natural phospholipids: sphingomyelin (Sph) and dipalmitoylphosphatidylglycerol (DPPG), which is much more specific than any lipid binding protein based complex falling within the scope of what is claimed (Abionyx, https://www.abionyx.com/en/our-assets/cer-001, last visited 09/30/2026).
While the prior art recognized various HDL mimetics (See WO2021/209823 from ISR entire document; Kruger et al., abstract), the claims and the application do not specify what complexes have the specific activity to be used in the claimed method.
As such, the claimed complex does not contain sufficient identifying characteristics to be considered relevant structural features linked to function, and there is no supporting data provided for any examples outside of CER-001, and no supporting information regarding support from what is known in the art regarding how this “peptide-based” feature relates to the required functionality of lipid binding, or any of the required functions in the more complex methods of treatment functionality.
(d) Representative number of examples
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)("[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.").
One example of CER-001 reduced to practice and several similar embodiments does not cover the entirety of the broad embodiments discussed for the HDL mimetic, which span para. 047-049, and include many different classes of lipid binding protein formulations and their many variations, which have many different properties and this section primarily describe and the lipids to which the claimed protein-based complexes can bind to, but not the actual complex to be administered or the required functional portion the is responsible for the claimed functions.
Given this lack of description in the specification, the application fails to describe the claimed invention in such a full, clear, and concise and exact terms that a skilled artisan would recognize that applicants were in possession of the genus of claimed invention.
Claim Rejections 35 USC 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 19, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections 35 USC 102(A)(1)
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-5, 18-22, 28, 52 and 54 are rejected under 35 U.S.C. 102(A)(1) as being anticipated by Tanaka et al. (Biomedicines 2022, 10, 754. Published on 03/03/2022).
Tanka teaches that High Density Lipoproteins, such as rHDL particles has have multiple endothelioprotective properties, and that upon SARS-CoV-2 infection, a subject’s HDL-cholesterol (HDL-C) concentration is markedly reduced, and functionality of HDL particles are severely impaired. These reference teaches a multi-omic investigation of administration of recombinant HDL (rHDL) particles in a severe COVID 19 patient found that plasma ApoA1 was increased and HDL-C was decreased after each recombinant HDL injection, suggesting that these particles were functional in terms of reverse cholesterol transport (Abstract). Additionally, ApoA1 was more abundant after injections, whereas most of the pro-inflammatory proteins identified were less abundant, showing that recombinant HDL infusion is feasible and a potential therapeutic strategy to be explored in COVID-19 patients (abstract).
Tanaka teaches that in addition to their reverse cholesterol transport function, HDLs exhibit pleiotropic endothelioprotective properties, including anti-inflammatory, anti-apoptotic, anti-thrombotic, and antioxidant functions (p. 2, para. 1). This reference teaches that HDLs also have the ability to neutralize lipopolysaccharide (LPS) and promote its clearance, giving them anti-infectious effects and during acute inflammatory states, clinical studies have shown that HDL-cholesterol (HDL-C) levels are low (p. 2, para. 1). This reference teaches that the HDL profile of COVID-19 patients is similar to that of patients with bacterial sepsis with a drastic decrease in HDL-C concentration, changes in HDL proteome and size, and impaired protective effects, supporting the therapeutic potential of administering functional HDL particles in COVID-19 patients (p. 2, para. 3). This reference further teaches that pharmaceutical companies have developed apoA1 nanoparticles reconstituted from recombinant ApoA1 or ApoA1 isolated from human plasma in combination with phospholipids (rHDL), including CER-001.
Tanaka teaches that administration of the rHDL therapeutic, CER-001, to an overweight subject having hypothyroidism, and chronic obstructive pulmonary disease, who had severe COVID-19 requiring high-flow oxygen therapy alternating with noninvasive ventilation on admission to mitigate severe hypoxemia (p. 2, section 2.1). This reference teaches that rHDLs were injected intravenously every 12 h for 3 consecutive days and EDTA plasma was collected before (H0, H12) and 3 h after rHDL injection (H3 and H15) (spanning p. 2-3, sec. 2.1). This reference further teaches that the patient’s respiratory function was relatively stable during CER-001 treatment with high-flow oxygen therapy and noninvasive ventilation P. 3, 2.1).
Claim Interpretation
Claim 1 is drawn to a method of treating symptoms associated with leukocytosis, not to a method of treating leukocytosis itself. Dependent claim 4 further supports this interpretation by allowing the subject to be at risk for leukocytosis due to inflammation, an infection, a white blood cell count disorder, physical stress, emotional stress, medication or an allergic reaction. As such, being at risk for anything that may eventually cause leukocytosis, including infection, physical or emotion stress, medication, etc., will necessarily include the entire population of subjects to which the lipid binding protein based complex is administered, as all subjects are at risk for a potential causes of leukocytosis and its associated symptoms.
When it comes to the dependent claims 5-9, the subject must “have” one of the underlying diseases that is causing the symptoms of leukocytosis, even if the subject does not have leukocytosis, as this is a very fluid condition that simply means a high leukocyte count. These conditions (infection, diabetes, etc.) may be entirely unrelated to the leukocytosis associated symptom, as they depend from claim 1.
As such, administering CER-001 to a subject having any symptom of leukocytosis meets claims 1 and 4, and Tanaka teaches that the subject has a COVID-19 infection with symptoms (trouble breathing) associated with leukocytosis, which meets this limitation regardless of whether the subject currently has leukocytosis. Claim 2 is met because the subject was having trouble breathing as the symptom. Claim 3 is met because the subject had stable respiration during the rHDL administration, which meets the very broad definition of “ameliorating” a symptom associated with leukocytosis because there is no level of leukocytosis required, no required dose, no specific symptom or underlying condition in the claims that is required, and no clear measurement for efficacy or a definition of amelioration. Claim 4 is met because the subject has an infection and meets the broad patient class of “at risk” for symptoms of leukocytosis. Claim 5 is met because the subject has a COVID-19 infection.
Claims 18-22 are met because the definition of a subject “at risk” for carditis does not mean that the subject must have carditis, only that the subject may get it in the future, which is satisfied by the administration step. Claim 19 is met because the subject must have an infection, including COVID-19, thus Tanaka meets the limitations of this claim. Claim 28 is met because CER-001 contains ApoA-1 with other lipids. Claims 20-22 are also met because there is no actual dosage provided to any subject may have carditis prevented by the administration of the dosage of Tanaka, which was .80 and .85 g/L injections 3 time per day. Similarly, claim 54 is met because there is no dosage claimed, and any dosage is a prophylactic treatment in subject at risk for carditis or at risk for cause of it, such as infection. Claim 52 is met because the CER-001 was administered every 12 hours (twice/day). Claim 54 is met because the active method step of administering the same composition to the same patient class is met. The future effect of the WBC count is inherent to a method of administering the complex to a subject having a symptom, where the shortness of breath as a symptom is present in the subject.
Claim(s) 12, 18 and 20-22 are rejected under 35 U.S.C. 102(A)(1) as being anticipated by Kruger et al. (Circulation. 2005;111:3126-3134).
Kruger teaches that D-4F (a known HDL-mimetic) provides antioxidant effects in a diabetic model (abstract). This reference teaches that Sprague-Dawley rats developed diabetes with administration of streptozotocin (STZ), and then the Apolipoprotein A1 mimetic, D-4F was administered via intraperitoneal injection, daily to examine the effects of daily D-4 at 100 g/100 g of body weight on a diabetic rat model (abstract). This reference further teaches the vascular protective effect of D-4F administration by decreasing endothelial cell sloughing and debris, which is a type of vascular endothelial dysfunction, as this reference teaches that many of the significant clinical problems associated with diabetes are traced to vascular damage induced by hyperglycemia from diabetes, which increases the sloughing and fragmentation of endothelial cells typically found with diabetes (p. 3131, Col. 2). This reference teaches that in the animals to which D-F4 was administered, the endothelial cell dysfunction was lessened from that which is typically present in diabetes (p. 131, col. 2).
Claims 12 because this reference teaches treating endothelial dysfunction. Claims 18-22 are met for the same reasons discussed in the above rejection over Tanka, because the subject does not need to have carditis, only to be at risk for it.
Claim(s) 1-5, 7, 18-22, 28, 33, and 52-54 are rejected under 35 U.S.C. 102(A)(1) as being anticipated by Tupin et al. (WO2021/09823A1).
Tupin teaches method of treating acute conditions with lipid binding protein complexes (abstract) This reference teaches that such conditions include risk factors, such as diabetes, and sepsis with CER-001 [0012-0014; 0024-0025]. Specifically, this reference teaches that the method comprises administering a high dose of the lipid binding protein- based complex to a subject in need thereof, optionally wherein the acute condition comprises acute inflammation (Claim 1).
This meets the limitations of instant claims 1-5 and 7 because the reference teaches treating inflammation with CER-001 and other lipid binding protein-based complexes, which is associated with leukocytosis and diabetes, and is a risk factor for WBC count variations. Claims 18-22, 28 and 54 are met as discussed above, as the claimed method is for those ‘at risk,” for these conditions. Claim 33 is met because SEQ ID NO: 2 is identical to SEQ ID NO: 2 of Tupin. Claims 52-53 are met because Tupin teaches administration twice per day (claim 4), and for 5 days, (claim 2). Claim 54 is met, as discussed above, because the same lipid-binding protein-based complex is administered to the same patient population for the same preventative reasons in at risk subjects.
Claim Rejections 35 USC 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-5, 7-10, 18-22 and 28, 33 and 52-54 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tanaka as applied to claims 1-5, 18-22, 28 and 52 above, in view of WO2021/209823 (see ISR).
The difference between the prior art and the instant claims is that the prior art does not teach treating a subject having a WBC disorder or leukocytosis.
However, Tupin teaches also teaches methods of treating various conditions that are associated with abnormal white blood cell counts, such as cytokine release syndrome (CRS). This reference teaches that various acute conditions associated with acute inflammation such as sepsis, acute kidney injury (AKI), and cytokine release syndrome (CRS) are common and potentially life threatening conditions, which can be treated with lipid binding protein-based complexes (e.g., CER-001).
As such, it would have been obvious to treat WBC disorders and leukocytosis in the method of Tupin because a cytokine storm is associated with both white blood cell count and leukocytosis, and both entail abnormal inflammatory responses that would cause the associated inflammatory fluctuation in WBCs. One would be motivated to treat subject having an infection and CRS with a lipid binding protein-based complex because as the subjects would be expected to also have WBC abnormalities due to the overlapping and fluid nature of a subject having over 11x10 per liter WBC, which is the naturally occurring upper limit of the normal WBC (See CDC DHHS Publication No. (PHS) 82-1670, 1982; https://www.cdc.gov/nchs/data/series/sr_11/sr11_220.pdf last visited 09/30/26).
As such, there is a reasonable expectation of success that subject having abnormal WBC can be treated for symptoms and conditions associated with s subject having leukocytosis or a white blood cell count disorder, which renders obvious claims 8-10.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANETTE M LIEB whose telephone number is (571)270-3490. The examiner can normally be reached M-F 10-7.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654
