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 .
The Examiner of your application in the USPTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Art Unit 1671, Examiner Nianxiang (Nick) Zou.
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Apr. 24, 2026. Claims 1, 4, 6-12, 15-16, 29-31 and 40-44 are pending and currently examined.
Election/Restrictions
In response to Applicant’s request, it is formally stated that the Office action mailed on Jul. 2, 2025 has been vacated in favor of the Office action mailed on Mar. 11, 2026. Applicant’s response filed on Nov. 10, 2025 to the Office action mailed on Jul. 2, 2025 is disregarded.
Applicant's election without traverse in the reply filed on Apr. 24, 2026 is acknowledged. The following species have been elected:
1) inflammatory disease,
2) infectious disease mediated by respiratory viruses recited in claim 10,
3) COVID19 recited in claim 41,
4) malondialdehyde-modified proteins recited in claim 15,
5) SEQ ID NOs: 1-6 recited in claim 16,
6) Additional agent (a): an inhibitor/antagonist of the Angiotensin-II-type 1 receptor (ATIR); Additional agent (b): a compound inhibiting/antagonizing/neutralizing ligands of receptor of advanced glycation endproducts (RAGE); additional agent (c): Granulocyte-macrophage colony-stimulating factor (GM-CSF),
7) umifenovir recited in claim 43, and
8) an antibody that binds to IL-6 recited in claim 44.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1, 4, 6-12, 15-16, 29-31 and 40-44 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The base claim 1 recites:
“A method of treating or preventing a disorder or disease associated with/related to/caused by a natural IgM/IgA antibody deficiency (NAD) in a subject, comprising administration of a composition comprising an effective amount of at least one human or humanized natural IgM and/or IgA antibody recognizing said oxidized phospholipids and/or oxidation-specific epitopes,
wherein said disorder or disease is selected from at least one of the group consisting of a natural antibody deficient infectious disease, inflammatory disease, neurodegenerative disease, metabolic disease, autoimmune disease, and cardiovascular disease,
wherein each said human natural IgM and/or IgA antibody is from a subgroup of the total IgM and/or IgA repertoire of at least one source, said subgroup essentially consisting of antibodies recognizing oxidized phospholipids and/or oxidation-specific epitopes, and
wherein said composition contains more than about 35% said human or humanized natural IgM and/or IgA antibody recognizing oxidized phospholipids and/or oxidation-specific epitopes.”
Claim 1 is not clear in at least the following aspects.
A. Claim 1 appears to require that the subject to be treated by the claimed invention be with “a disorder or disease associated with/related to/caused by a natural IgM/IgA antibody deficiency (NAD).” However, even though the phrase “a disorder or disease associated with/related to/caused by a natural IgM/IgA antibody deficiency (NAD)” is mentioned throughout the disclosure, neither the specification or claims clearly and exclusively define how this limitation should be interpreted.
E.g., claim 1 specifies that the “disorder or disease is selected from at least one of the group consisting of a natural antibody deficient infectious disease, inflammatory disease, neurodegenerative disease, metabolic disease, autoimmune disease, and cardiovascular disease”, but neither the specification nor the claim specify how to determine if a “disorder or disease” as recited is natural antibody deficient. The specification provides a few examples based on SARS-CoV-2 infections, but does not provide evidence that patients with SARS-CoV-2 infection must be natural antibody deficient, or how SARS-CoV-2 infections, at any stage, are “associated with/related to/caused by a natural IgM/IgA antibody deficiency (NAD)”, as specified in claim 1.
In other words, it is not clear how to determine if a disorder or disease that needs to be treated by the administration of the claimed composition is “associated with/related to/caused by a natural IgM/IgA antibody deficiency (NAD)”, or is a “natural antibody deficient” disorder or disease.
B. Claim 1 recites “said oxidized phospholipids and/or oxidation-specific epitopes”. This limitation does not have antecedent basis.
C. Claim 1 recites “wherein said composition contains more than about 35% said human or humanized natural IgM and/or IgA antibody recognizing oxidized phospholipids and/or oxidation-specific epitopes.” Here, the word “about” renders the claim unclear because it is not clear what value is considered as encompassed by “about 35%” and what is not.
Additionally, it is not clear how the % value should be calculated. E.g., it is not clear if the percentage value is calculated against the entire amount of the claimed composition or any active ingredient. Paragraphs [0066]-[0067] of the instant specification describe about contents in percentage values for “human or humanized natural IgM and/or IgA antibody recognizing oxidized phospholipids and/or oxidation-specific epitopes”. See below:
[0066] Preferably, the term "pure" or "essentially consisting of' means that a composition comprising said human or humanized natural IgM and/or IgA antibody of the present invention contains more than 30% antibodies recognizing oxidized phospholipids and/or oxidation-specific epitopes of the total IgM and/or IgA antibodies in said composition, preferably more than 35%, 40%, 50%, 60%, 70%, 80%, 90%, 99% or 100%.
[0067] In other preferred embodiments, the term "pure" means that a composition comprising said human or humanized natural IgM and/or IgA antibody of the present invention contains between 30% and 100% antibodies recognizing oxidized phospholipids and/or oxidation-specific epitopes of the total IgM and/or IgA antibodies in said composition, preferably between 35% and 100%, between 40% and 100%, between 50% and 100%, between 60% and 100%, between 70% and 100%, between 80% and 100%, between 90% and 100% or between 99% and 100%.
These teachings provide an approach for calculation of a percentage value for the IgM and/or IgA antibody recognizing oxidized phospholipids and/or oxidation-specific epitopes, which appears to be done against the overall IgM/IgA amount in the composition.
To facilitate examination, claim 1 is interpreted based on the definition that any disorder or disease is considered as being “associated with/related to/caused by a natural IgM/IgA antibody deficiency (NAD)” and being “natural antibody deficient”, if a treatment as claimed is administered to the subject with the disorder or disease with a positive therapeutic result (based on the assumption that the claimed natural IgM/IgA antibody supplements to the subject’s immune system in the treatment of the disorder or disease). The claimed percentage value, i.e., more than about 35%, is interpreted as representing the ratio between the IgM and/or IgA antibodies recognizing oxidized phospholipids and/or oxidation-specific epitopes and the overall IgM/IgA antibodies in the claimed composition.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Claim 4 recites “wherein said source is at least one healthy individual and said subgroup of IgM and/or IgA antibodies is derived from IgM and/or IgA enriched plasma pools from said at least one healthy individual, said subgroup essentially consisting of antibodies recognizing oxidized phospholipids and/or oxidation-specific epitopes.” Here, the terms “said source”, “said subgroup of IgM and/or IgA antibodies”, and “said at least one healthy individual” do not have antecedent basis.
Claim Rejections - 35 USC § 112(a) (Written Description)
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.
Claims 1, 4, 6-12, 15-16, 29-31 and 40-44 are rejected under 35 U.S.C. 112(a) 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, at the time the application was filed, had possession of the claimed invention.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings. See MPEP 2163. I.
The claims are drawn to a method of treating or preventing disorder or disease associated with/related to/caused by a natural IgM/IgA antibody deficiency (NAD) in a subject, comprising administering a composition comprising an effective amount of at least one human or humanized natural IgM and/or IgA antibody recognizing said oxidized phospholipids and/or oxidation-specific epitopes. The disorder/disease to be treated or prevented encompass a number of highly different diseases. The specification teaches study results obtained by using commercially available IgM/IgG-enriched pooled human plasma product, Pentaglobin (which is expected to contain a high ratio of IgM recognizing OSEs), and monoclonal antibodies recognizing oxidation-specific epitopes (OSEs) in the treatment of SARS-CoV-2 infection. The specification does not provide evidence that administration of such IgM/IgA can prevent any disorder or disease as claimed.
It is known in the art that naturally occurring innate IgM antibody in human (and mouse) contains antibody molecules recognizing host’s self OSEs as well as other autoantigens potentially associated with a number of disorders/diseases caused by over reaction of innate immunities, and that such properties have been shown to be helpful in treatment of certain diseases associated with innate immune response. See discussions in the art rejections below. No evidence is found that naturally occurring innate IgM/IgA enriched in IgM or humanized antibodies recognizing OSEs are effective in preventing a disorder/disease, or at least in preventing the large variety of disorders/diseases, as claimed.
The Specification does not give sufficient guidance on how such naturally occurring IgM/IgA antibodies with OSE-recognizing activities can be used to prevent the claimed disorders/diseases. Specification does not show evidence that such an IgM/IgA composition has worked in a process at the full scope according to the claims.
Accordingly, the specification does not provide written description support that the Applicant is in possession of the invention in the full scope as claimed.
Claim Rejections - 35 USC § 112 (Scope of Enablement)
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.
Claims 1, 4, 6-12, 15-16, 29-31 and 40-44 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a method of treating a disorder or disease associated with/related to/caused by a natural IgM/IgA antibody deficiency (NAD) in a subject, does not reasonably provide enablement for a method of preventing a disorder or disease as claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)).
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965).
Analysis of the claimed invention is presented in the 112 written description rejection above, addressing nature of the invention, state of the prior art, working examples, and guidance in the specification. See discussions above.
Taking together all the considerations, there is insufficient disclosure for an average researcher in the field to reasonably predict that a composition as claimed would have the property of preventing the wide variety of disorders/diseases as claimed.
Accordingly, when all the aforementioned factors are considered in total, it would require undue experimentation for one skilled in the art to practice the full scope of claimed invention as defined by instant claims.
Claim Rejections - 35 USC § 102
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.
Claims 1, 4, 7-10, 12, 15 and 40 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Borleffs et al. (Eur J Clin Microbiol Infect Dis. 1993;12(10): 772-5), as evidenced by Binder (Adv Exp Med Biol. 2012:750:2-13).
The base claim 1 is described and interpreted in the 112(b) rejection above.
Borleffs teaches a study on treatment of two hypogammaglobulinemic patients with persistent Campylobacter jejuni infections in spite of IgG substitution and antibiotic therapy. Since serum bactericidal activity (SBA) depends on IgM, these patients were each treated with six doses of an IgM-containing immunoglobulin preparation (Pentaglobin) at three-week intervals. During IgG therapy SBA was not seen in either patient. However, one hour following administration of the IgM preparation SBA increased to 90 %. Just before the next dose SBA was still at the 30-70 % level. Both patients tolerated the therapy very well and there were no culture-confirmed relapses of Campylobacter jejuni infection. The IgM preparation may therefore be a useful alternative to conventional IgG in the treatment of hypogammaglobulinemic patients with persistent Campylobacter jejuni infection. See Abstract.
Borleffs teaches that, in view of the morbidity caused by these recurrent Campylobacter jejuni infections, a decision was made to give experimental treatment with an IgM-containing preparation (Pentaglobin, Biotest Pharma, Germany), and that the patients were administered 350 mg/kg body weight (i.e. 500 ml) of the preparation intravenously at three-week intervals. See page 773, left column, para 2. Borleffs teaches that in both patients a positive effect was clearly seen in both quantitative and qualitative laboratory parameters, and that IgM-containing immunoglobulins may be an important adjunct in substitution therapy of patients with hypogammaglobulinemia with recurrent bacterial infections. See page 775, left column.
Accordingly, Borleffs teaches a method for treating a disorder/disease (here, hypogammaglobulinemia and recurrent bacterial infections) in a subject, comprising administration of a composition, Pentaglubin, which comprises IgM and IgA.
Based on the teachings of the instant specification, Pentaglobin® is a commercially available IVIG specifically enriched in IgM and IgA. Active ingredients of Pentaglobin® are human plasma proteins (50 mg/ml), of which at least 95% are immunoglobulins with immunoglobulin G (IgG) 38 mg (76%), immunoglobulin M (IgM) 6 mg (12%), and immunoglobulin A (IgA) 6 mg (12%). See [0113] of instant specification. The instant specification teaches that the human or humanized natural IgM and/or IgA antibody recognizing oxidized phospholipids and/or oxidation-specific epitopes can be derived from Pentaglobin®. See [0118]. These teachings indicate that Pentaglobin, used in the study of Borleffs, is enriched in natural IgM and IgA and contains antibodies recognizing oxidized phospholipids and/or oxidation-specific epitopes.
Binder reviews about naturally occurring IgM antibodies to oxidation-specific epitopes. It teaches that naturally occurring antibodies (NAbs) have specificity for both microbial and self antigens, which allows them to act in the first line defense against invading pathogens, as well as in tissue homeostasis by mediating the clearance of cellular debris. Binder teaches that oxidation-specific epitopes are dominant targets of naturally occurring IgM antibodies. See Abstract. Binder teaches that multiple lines of evidence show that oxidation-epitopes are major targets of IgM NAbs in mice and humans and that antigen absorption studies with plasma of reconstituted mice showed that as much as 30% of all plasma IgM had specificity for various oxidation-epitopes. See page 6, para 1. Binder teaches that IgM antibodies in human umbilical cord blood bind the surface of apoptotic cells and approximately 50% of this binding could be competed by soluble MDA-BSA, suggesting that the binding of IgM NAbs is to a large extent mediated by the recognition of MDA-epitopes (a type of oxidation-specific epitopes (OSE)). See page 7, para 1. Binder further teaches that the observation that more than 30% of all naturally occurring IgM antibodies are directed against oxidation-epitopes, suggests that a major part of the protective effect is mediated by this specific subset of NAbs, because products of lipid peroxidation are key mediators of the atherosclerotic disease process. See page 9, para 1. Accordingly, teachings of Binder indicate that more than 30% of all naturally occurring IgM antibodies are directed against oxidation-specific epitopes.
Based on the teachings of Binder and given the teachings in the instant Specification, it is reasonable to expect that the Pentaglobin, a commercial IgM/IgA enrich plasma product used in the study of Borleffs, contains more than about 35% human natural IgM and/or IgA antibody recognizing oxidized phospholipids and/or oxidation-specific epitopes, with the percentage value interpreted as described in the 112(b) rejection above.
The Office does not have the facilities and resources to provide the factual evidence needed in order to establish that the Pentaglobin taught in Borleffs does not contain more than about 35% of human or humanized natural IgM and/or IgA antibody recognizing oxidized phospholipids and/or oxidation-specific epitopes. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed composition is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Regarding claim 4, the commercially available Pentaglobin contains IgM/IgA enriched plasma pools from multiple healthy human individuals.
Regarding claims 7-8, 15 and 40, since the Pentaglobin used in Borleffs is not distinguishable from the one relied upon in the instant invention, it is considered to have the same properties, such as containing human natural IgM and/or IgA antibody capable of inhibiting the cell-to-cell spread of a virus from an infected cell to an adjacent non-infected cell (claim 7), having an anti-inflammatory activity (claims 8 and 40), and recognizing the claimed epitopes (claim 15).
Regarding claims 9-10, bacterium Campylobacter jejuni infection is associated with inflammation responses.
Regarding claim 12, the limitation “at least one pharmaceutically acceptable excipient” reads on many components in Pentaglobin, such as water and salts.
Therefore, based on the interpretation of the claims in the 112(b) rejection above, Borleffs anticipates claims 1, 4, 7-10, 12, 15, 29 and 40.
Claims 1, 4, 7-12, 15, 29 and 40-42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ho et al. (Int J Tuberc Lung Dis. 2004 Oct; 8(10):1173-9), as evidenced by Binder (Adv Exp Med Biol. 2012:750:2-13).
This rejection addresses the elected species of respiratory virus infection, more specifically, coronavirus infection, for the disorder/disease to be treated by the claimed method.
Ho teaches a study to determine the clinical efficacy of Pentaglobin, an IgM-enriched immunoglobulin preparation, on 12 severe SARS patients who continued to deteriorate despite corticosteroid and ribavirin therapy. Ho teaches that there was significant improvement in radiographic scores, when compared with day 1, on days 5, 6 and 7 (P < 0.05) after commencement of pentaglobin treatment; that there was significant improvement in oxygen requirement, when compared with day 1, on days 6 and 7 (P < 0.05) after commencement of pentaglobin treatment. Ho teaches that there were no reported adverse events attributable to pentaglobin administration; that ten patients made an uneventful recovery after treatment; and that one elderly man died from cardiorespiratory arrest despite clinical and radiological improvement, and another patient is making good progress. Ho concludes that Pentaglobin is safe and probably effective in the treatment of steroid-resistant SARS, and that a double-blind placebo-controlled study should therefore be considered. See Abstract.
Ho teaches that intravenous immunoglobulins (IVIg) have been shown to be beneficial in the treatment of many autoimmune and inflammatory conditions, that in vitro data suggest that cytokine modulation might be responsible for the therapeutic efficacy of IVIg. Ho teaches that Pemaglobin is a commercially available Mg specifically enriched for immunoglobulin (Ig) M, that the higher concentration of IgM might theoretically enhance its immunomodulatory effect, and that the authors therefore administered pentaglobin to a cohort of SARS patients who did not show favourable response to treatment with pulse methylprednisolone therapy. See para spanning pages 1173-1174.
Accordingly, Ho teaches a method for treating a SARS-CoV infection in patients who do not respond well to steroid treatment, comprising administering to the patients an IgM/IgA enriched plasma product, Pentaglobin, and observed promising positive results.
According to the discussion in the 102 rejection over Borleffs above, Pentaglobin is expected to be indistinguishable from the composition as claimed.
Additional rationales for rejection of dependent claims 4, 7-10, 12, 15 and 40 are the same as described in the 102 rejection over Borleffs above.
Therefore, based on the interpretation of the claims in the 112(b) rejection above, Ho anticipated claims 1, 4, 7-12, 15, 29 and 40-42.
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 of this title, 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.
Claims 6, 30-31 and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Ho et al. (Int J Tuberc Lung Dis. 2004 Oct; 8(10):1173-9), as evidenced by Binder (Adv Exp Med Biol. 2012:750:2-13), as applied above, in view of Zhou et al. (bioRxiv 2020.02.12.945576; posted February 20, 2020) and/or Blaising et al. (Antiviral Research 107 (2014) 84–94).
Claim 6 specifies that the disorder/disease to be treated is COVID-19 caused by SARS-CoV-2. Claims 30 and 43 specify that administration is in combination with an antiviral compound, and specifically with umifenofir as elected species. Claims 31 and 44 specify that administration is in combination with an immunomodulator, and specifically with antibody against GM-CSF or antibody against IL-6 as elected species.
Relevance of Ho and Binder is set forth in the 102 rejection above. However, even though Ho teaches treatment of SARS-CoV with Pentaglobin, which is indistinguishable from the composition as claimed, it is silent on SARS-CoV-2, specified in claim 6, which is another human coronavirus causing severe respiratory syndromes; Ho is silent on combination of the Pentaglobin with an antiviral compound or immunomodulator.
Zhou teaches that pathogenic human coronavirus infections, such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV), cause high morbidity and mortality. Recently, a severe pneumonia-associated respiratory syndrome caused by a new coronavirus was reported at December 2019 (2019-nCoV) in the city Wuhan, Hubei province, China. Up to 9th of February 2020, at least 37, 251 cases have been reported with 812 fatal cases according to the report from China CDC. However, the immune mechanism that potential orchestrated acute mortality from patients of 2019-nCoV is still unknown. Here the authors show that after the 2019-nCoV infection, CD4+T lymphocytes are rapidly activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF etc. The cytokines environment induces inflammatory CD14+CD16+ monocytes with high expression of IL-6 and accelerates the inflammation. These aberrant and excessive immune cells may enter the pulmonary circulation in huge numbers and play an immune damaging role to causing lung functional disability and quick mortality. The results demonstrate that excessive non-effective host immune responses by pathogenic T cells and inflammatory monocytes may associate with severe lung pathology. Therefore, they suggest that monoclonal antibody that targets the GM-CSF or interleukin 6 receptor may potentially curb immunopathology caused by 2019-nCoV and consequently win more time for virus clearance. See Abstract.
Blaising review about Arbidol (umifenovir) as a broad-spectrum antiviral. Arbidol (ARB) is a Russian-made small indole-derivative molecule, licensed in Russia and China for prophylaxis and treatment of influenza and other respiratory viral infections. It also demonstrates inhibitory activity against other viruses, enveloped or not, responsible for emerging or globally prevalent infectious diseases such as hepatitis B and C, gastroenteritis, hemorrhagic fevers or encephalitis. See Abstract.
Accordingly, teachings of Zhou suggest that immunomodulators, such as monoclonal antibodies against GM-CSF or IL-6 receptor, may potentially be applied in the treatment of 2019-nCoV (SARS-CoV-2) infection (COVID-19), a disease which is comparable with that caused by SARS-CoV. Teachings of Blaising indicate that the antiviral compound Arbidol (umifenovir) is a broad-spectrum antiviral that can be used in treating many highly different viruses, including viruses causing respiratory infections.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to combine the teachings of Ho and Zhou and/or Blaising to arrive at the invention as claimed. For claim 6, one would have been motivated to do so to introduce the Pentaglubin, which has been shown to be effective in treating SARS-CoV infection in the study of Ho, into treatment of SARS-CoV-2, taught in Zhou to evaluate the effect of Pentaglobin in treating COVID-19; and for claims 30-31 and 43-44, one would have been motivated to introduce the immunomodulator treatment taught in Zhou or the antiviral treatment taught in Braising, into the study of Ho to evaluate to effect of combination of Pentaglobin with immunomodulator or antiviral in the treatment of SARS-CoV infection. There would be a reasonable expectation of success that such combination studies can be performed and effective results be observed based on the teachings of the cited prior art.
Relevant References Not Used in Rejections
The following prior art references not relied upon in the current rejections are made of record here:
1) van Leeuwen et al. Passive Immunization with Hypochlorite-oxLDL Specific Antibodies Reduces Plaque Volume in LDL Receptor-Deficient Mice. PLoS ONE 8(7): e68039. doi:10.1371/journal.pone.0068039.
2) Tsimikas et al. (US 2019/0225709 A1, published Jul. 25, 2019).
Teachings of van Leeuwen and Tsimikas associate naturally occurring OSE-recognizing IgM antibodies with certain disease conditions including cardiovascular conditions, liver conditions, etc.. Both references teach the production of monoclonal antibodies recognizing OSEs and propose the application of such OSE-recognizing IgM antibodies in the treatment of diseases in human.
Conclusion
No claims are allowed.
Claim 16 is objected to for depending from a rejected claim.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671
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