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 .
Status of the Claims
Claims 1-20 are currently pending and under examination.
Priority
The present application claims priority to U.S. Provisional Patent Application No. 63/369,100, filed on July 22, 2022.
Claim Objections
Claim 11 is objected to because it is missing a period at the end of the claim. Claims should end with a period; see MPEP 608.01(i). Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-6 and 8-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the treatment of SARS-COV-2 infection comprising administering an effective amount of mycolactone, does not reasonably provide enablement for the treatment or prevention of other microbial infections. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention is drawn to the use of mycolactone to treat or prevent microbial infections. Claims 1-6 and 8-13 are drawn generally to a method of treating an infection in a subject, comprising administering a composition containing mycolactone to the subject. Claims 14-20 are drawn generally to a method of preventing an infection in a subject, comprising administering a composition containing mycolactone to the subject. Claims 1 and 14 are drawn to treating or preventing any microbial infection. Claims 2 and 15 are drawn to treating or preventing a viral infection. Claims 3 and 16 are drawn to treating or preventing infection from an enveloped virus. Claims 4 and 17 are drawn to treating or preventing infection from an RNA virus. Claims 5 and 18 are drawn to treating or preventing a coronavirus infection. Claims 6 and 19 are drawn to treating or preventing infection from SARS-CoV-2, SARS-CoV-1, MERSCoV, HCoV-229E, HCoV-OC43, HCoV-NL63, or HCoV-HKUl. Claim 20 is drawn to preventing a SARS-CoV-2 infection. Claim 8 is drawn to treating a flavivirus infection. Claim 9 is drawn to treating infection from Zika virus, Dengue fever virus, yellow fever virus, Hepatitis C virus, West Nile virus, tick-borne encephalitis virus, Saint Louis encephalitis virus, or GB virus C. Claim 10 is drawn to treating filovirus infections. Claim 11 is drawn to treating an Ebola virus infection. Claim 12 is drawn to treating a bacterial infection. Claim 13 is drawn to treating a fungal infection.
The specification defines “treatment” as administering a compound to ameliorate symptoms of disease. The specification also defines “treatment” to refer to prophylaxis, i.e., treating a patient who is susceptible to a disease or disorder. The specification defines “prevention” as delaying or forestalling the development or progression of a disease.
The relative skill of those in the art is high, generally that of a M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain).
At the time the instant application was filed, the state of the art of treating a bacterial infection as recited in claims 1 and 12 embraces treatment of the following unrelated diseases and/or infections caused by the following bacteria (without limitation, because the claim is open-ended and embraces any infection caused by any bacteria): Acute post-streptococcal glomerulonephritis (APSGN), Acute rheumatic fever, Anthrax, Botulism, Brucellosis, Campylobacter, Cholera, Diarrhea, Diphtheria, Escherichia coli, Gastroenteritis, Haemophilus influenzae type b (hib), Invasive Group A Streptococcal (iGAS) disease, Legionnaires' disease, Leptospirosis, Listeriosis, Melioidosis, Meningitis (all types), Meningococcal disease, Mycobacterium chimaera, Mycoplasma pneumoniae, Pneumococcal disease, Psittacosis, Q fever, Rheumatic heart disease, Salmonella infection (salmonellosis), Shiga toxin-producing e. coli (stec) and haemolytic uraemic syndrome (hus), Shigella infection (shigellosis), Staphylococcus aureus infection, Tetanus, Toxic shock syndrome, Trachoma, Typhoid and paratyphoid fever, Vibrio vulnificus infection, Whooping cough (pertussis), Yersiniosis, etc some of which are extremely unpredictable and difficult to treat, and not enabled by the disclosure. In the instant case, the instant claimed invention is highly unpredictable since one skilled in the art would recognize that in regards to therapeutic effects of the above listed infections/ diseases, whether or not the disease is affected by the inhibition of a certain bacteria would make a difference.
Similarly, the state of the prior art is that viral therapy remains highly unpredictable. The state of the art establishes that mycolactone is useful for treating. However, there are many types of virus:
Adenoviruses. The adenoviruses are divided into four genera: Mastadenovirus: Bovine adenovirus A, Bovine adenovirus B, Bovine adenovirus C, Canine adenovirus, Equine adenovirus A, Equine adenovirus B, Human adenovirus A, Human adenovirus B, Human adenovirus C, Human adenovirus D, Human adenovirus E, Human adenovirus F, Murine adenovirus A, Ovine adenovirus A, Ovine adenovirus B, Porcine adenovirus A, Porcine adenovirus B, Porcine adenovirus C, and Tree shrew adenovirus; Aviadenovirus: Fowl adenovirus A, Fowl adenovirus B, Fowl adenovirus C, Fowl adenovirus D, Fowl adenovirus E, and Goose adenovirus; Atadenovirus: Bovine adenovirus D, Duck adenovirus A, Ovine adenovirus D, and Possum adenovirus; and Siadenovirus: Frog adenovirus, Turkey adenovirus A.
In addition, there are further adenovirus serotypes. Thus, while there are 6 species of human adenovirus (Human adenovirus A-F), there are 51 immunologically distinct human adenovirus serotypes that can cause human infections ranging from respiratory disease, to conjunctivitis to gastroenteritis and possibly, obesity.
Hepadnaviruses. The hepadnaviruses consist of Ground squirrel hepatitis virus, Hepatitis B virus, Woodchuck hepatitis virus, Woolly monkey hepatitis B virus, Duck hepatitis B virus and Heron hepatitis B virus.
Flavivirus. The human Flavivirus (Positive Stranded ssRNA Virus) are a diverse lot, including the Pestiviruses (such as Classical swine fever (CSF) and Bovine viral diarrhoea / Mucosal disease (BVD/MD) ), Hepatitis C, Yellow fever virus, Gadgets Gully virus, Kadam virus, Kyasanur Forest disease virus, Langat virus, Omsk hemorrhagic fever virus, Powassan virus, Royal Farm virus, Tick-borne encephalitis virus, Meaban virus, Tyuleniy virus, Aroa virus, Dengue virus, Kedougou virus, Cacipacore virus, Koutango virus, Japanese encephalitis virus, Murray Valley encephalitis virus, St. Louis encephalitis virus, Usutu virus, West Nile virus, Kunjin virus, Ntaya virus, Uganda S virus, Apoi virus, Montana myotis leukoencephalitis virus, and many, many more.
Retroviruses. The retroviruses (ssRNA RT-Viruses) fall into seven different genuses. The first is Alpharetrovirus. These include the Avian leukosis virus (ALV) (which comes in two strains), Rous sarcoma virus (RSV), which has 3 strains, Avian carcinoma Mill Hill virus 2, Avian myeloblastosis virus, Avian myelocytomatosis virus 29, Avian sarcoma virus CT10, Fujinami sarcoma virus, UR2 sarcoma virus (also known as University of Rochester virus 2 and Avian sarcoma virus UR-2), and the Y73 sarcoma virus. The second genus is the Betaretrovirus. This include the Langur virus (LNGV), Mason-Pfizer monkey virus (which comes in 3 strains), Mouse mammary tumor virus, Ovine pulmonary adenocarcinoma virus, Jaagsiekte sheep retrovirus, and the Squirrel monkey retrovirus. The third genus is the Gammaretrovirus. This includes the Feline leukemia virus, Gibbon ape leukemia virus, Guinea pig type C oncovirus, Murine leukemia virus (which exists in at least 6 strains and isolates), Porcine type C oncovirus, Finkel-Biskis-Jinkins murine sarcoma, Gardner-Arnstein feline sarcoma virus, Hardy-Zuckerman feline sarcoma virus, Harvey murine sarcoma virus, Kirsten murine sarcoma virus, Moloney murine sarcoma virus, Snyder-Theilen feline sarcoma virus, Woolly monkey sarcoma virus, Viper retrovirus, Chick syncytial virus, Reticuloendotheliosis virus, and the Trager duck spleen necrosis virus. The fourth genus is the Deltaretrovirus. This includes the Bovine leukemia virus, Primate T-lymphotropic virus 1, Human T-lymphotropic virus 1 (HTLV-1), Simian T-lymphotropic virus 1 (STLV-1), Primate T-lymphotropic virus 2 (PTLV-2), Human T-lymphotropic virus 2 (HTLV-2), Simian T-lymphotropic virus 2 (STLV-2), and the Primate T-lymphotropic virus-3. The fifth genus is the Epsilonretrovirus. These include the Walleye dermal sarcoma virus, Walleye epidermal hyperplasia virus type 1, Walleye epidermal hyperplasia virus type 2, Perch hyperplasia virus, and the Snakehead retrovirus. The sixth Genus is the Lentivirus. This includes Bovine immunodeficiency virus, Equine infectious anemia virus, Feline immunodeficiency virus, Feline immunodeficiency virus (Oma), Puma lentivirus, Caprine arthritis encephalitis virus, Visna/maedi virus (which comes in 3 strains), Human immunodeficiency virus 1 (HIV-1, which comes is many strains), HIV-2, HIV-3, and Simian immunodeficiency virus (SIV) which comes in many strains, including African green monkey, chimpanzee SIV, mandrill SIV and others. The seventh genus is the Spumavirus. This includes Bovine foamy virus, Chimpanzee foamy virus, Feline foamy virus, Simian foamy virus 1 and Simian foamy virus 3.
Filovirus. The Filoviridae (Negative Stranded ssRNA) consists of the Marburg virus (which has 6 different strains), and the Ebola virus (which has 4 different strains).
Papovirus. The papillomaviruses are divided in to 16 genera: Alphapapillomavirus (Human papillomavirus 2, Human papillomavirus 6, Human papillomavirus 7, Human papillomavirus 10, Human papillomavirus 16, Human papillomavirus 18, Human papillomavirus 26, Human papillomavirus 32, Human papillomavirus 34, Human papillomavirus 53, Human papillomavirus 54, Human papillomavirus 61, Human papillomavirus 71, Human papillomavirus cand90, Rhesus monkey papillomavirus 1); Betapapillomavirus (Human papillomavirus 5, Human papillomavirus 9, Human papillomavirus 49, Human papillomavirus cand92, Human papillomavirus cand96); Gammapapillomavirus (Human papillomavirus 4, Human papillomavirus 48, Human papillomavirus 50, Human papillomavirus 60, Human papillomavirus 88); Deltapapillomavirus (Bovine papillomavirus 1, Deer papillomavirus, European elk papillomavirus, Ovine papillomavirus 1); Epsilonpapillomavirus (Bovine papillomavirus 5); Zetapapillomavirus (Equine papillomavirus 1); Etapapillomavirus (Fringilla coelebs papillomavirus); Thetapapillomavirus (Psittacus erithacus timneh papillomavirus); Iotapapillomavirus (Mastomys natalensis papillomavirus); Kappapapillomavirus (Cottontail rabbit papillomavirus, Rabbit oral papillomavirus); Lambdapapillomavirus (Canine oral papillomavirus, (Feline papillomavirus); Mupapillomavirus (Human papillomavirus 1, Human papillomavirus 63); Nupapillomavirus (Human papillomavirus 41); Xipapillomavirus(Bovine papillomavirus 3); Omicronpapillomavirus (Phocoena spinipinnis papillomavirus); and Pipapillomavirus (Hamster oral papillomavirus).
The Coronaviruses (positive-sense single-stranded) are sorted into three groups. Group 1: Canine coronavirus, Feline coronavirus, Feline infectious peritonitis virus, Human coronavirus 229E, Porcine epidemic diarrhea virus,Transmissible gastroenteritis virus, and Human Coronavirus NL63. Group 2: Bovine coronavirus, Canine respiratory coronavirus, Human coronavirus OC43, Human enteric coronavirus, Mouse hepatitis virus, Murine hepatitis virus, Puffinosis coronavirus, Porcine hemagglutinating encephalomyelitis virus, Rat coronavirus, Sialodacryoadenitis virus, and Severe Acute Respiratory Syndrome Coronavirus (SARS). Group 3 Avian infectious bronchitis virus, Rabbit coronavirus, Infectious bronchitis virus, and Turkey coronavirus (Bluecomb disease virus).
The Picornaviruses (single stranded, positive sense) are divided into 9 genera: 1. Enteroviruses (Bovine enterovirus, Human enterovirus A (21 types, including some coxsackie A viruses), Human enterovirus B (57 types, including assorted enteroviruses, coxsackie B viruses, echoviruses, and swine vesicular disease virus), Human enterovirus C (14 types including some coxsackie A viruses and enteroviruses), Human enterovirus D (2 types), Human enterovirus E Poliovirus (3 types), Porcine enterovirus A Porcine enterovirus B, and Simian enterovirus A(20 types). 2. Rhinoviruses (Human rhinovirus A, Human rhinovirus B). 3. Cardiovirus (Theiler's murine encephalomyellitis virus (TMEV), Vilyuisk human encephalomyelitis virus (VHEV), Theiler-like virus (TLV) of rats, Scaffold virus (SAFV-1 and SAFV-2), Columbia SK virus, Maus Elberfeld virus and Mengovirus). 4. Aphthovirus (Foot-and-mouth disease virus (in 10 forms) and Equine rhinitis A virus) 5. Hepatovirus (Hepatitis A virus, avian encephalomyelitis virus). 6. Parechovirus (Human parechovirus (HPeV) 1, HPeV-2, HPeV-3, HPeV-4, HPeV-5, HPeV-6 and Ljungan virus) 7. Erbovirus (equine rhinitis B virus (ERBV) 1, ERBV-2, ERBV-3) 8. Kobuvirus (Aichi virus, bovine kobuvirus) 9. Teschovirus (porcine teschovirus in 11 serotypes). In addition, there are numerous unassigned viruses that are normally placed with the Picronaviruses, including Acid-stable equine picornaviruses, Avian entero-like virus 2, Avian entero-like virus 3, Avian entero-like virus 4, Avian nephritis virus 3, Barramundi virus-1+, Cockatoo entero-like virus, Duck hepatitis virus 1, Duck hepatitis virus 3, Equine rhinovirus 3, Guineafowl transmissible enteritis virus, Harbour seal picorna-like virus, Sea-bass virus-1+, Sikhote-Alyn virus, Smelt virus-1+, Smelt virus-2+, Syr-Daria Valley fever virus, Taura syndrome virus of marine penaeid shrimp, Turbot virus-1, Turkey entero-like virus, Turkey hepatitis virus, Turkey pseudo enterovirus 1, and Turkey pseudo enterovirus 2.
Poxviruses are very large viruses about the size of small bacteria. They have a complex internal structure - a large double-stranded DNA genome (about 200 kbp in size) is enclosed within a "core" that is flanked by 2 "lateral bodies". The scope of pox viruses is quite extensive, in part because there are 11 genera: 1. Orthopoxvirus: Camelpox virus, Cowpox virus, Ectromelia virus, Monkeypox virus, Raccoonpox virus, Taterapox virus, Vaccinia virus (Vaccinia virus Ankara, Vaccinia virus Copenhagen, Vaccinia virus Tian Tan, Vaccinia virus WR, Buffalopox virus, Rabbitpox virus Utrecht, Cantagalo virus), Variola virus (Variola major virus Bangladesh-1975, Variola major virus India-1967, Variola virus minor Garcia-1966), Volepox virus. 2. Parapoxvirus: Bovine papular stomatitis virus, Orf virus, Parapoxvirus of red deer in New Zealand, Pseudocowpox virus, Squirrel parapoxvirus. 3. Avipoxvirus: Canarypox virus, Fowlpox virus, Juncopox virus, Mynahpox virus, Pigeonpox virus, Psittacinepox virus, Quailpox virus, Sparrowpox virus, Starlingpox virus, Turkeypox virus. 4. Capripoxvirus: Goatpox virus, Lumpy skin disease virus, Sheeppox virus. 5. Leporipoxvirus: Hare fibroma virus, Myxoma virus, Rabbit fibroma virus, Squirrel fibroma virus. 6. Suipoxvirus: Swinepox virus. 7. Molluscipoxvirus: Molluscum contagiosum virus. 8. Yatapoxvirus:Tanapox virus, Yaba monkey tumor virus. 9. Alphaentomopoxvirus: Anomala cuprea entomopoxvirus, Aphodius tasmaniae entomopoxvirus, Demodema boranensis entomopoxvirus, Dermolepida albohirtum entomopoxvirus, Figulus subleavis entomopoxvirus, Geotrupes sylvaticus entomopoxvirus, Melolontha entomopoxvirus, 10. Betaentomopoxvirus: Acrobasis zelleri entomopoxvirus 'L', Amsacta moorei entomopoxvirus 'L', Arphia conspersa entomopoxvirus 'O', Choristoneura biennis entomopoxvirus 'L', Choristoneura conflicta entomopoxvirus 'L', Choristoneura diversuma entomopoxvirus 'L', Choristoneura fumiferana entomopoxvirus ‘L’, Chorizagrotis auxiliars entomopoxvirus 'L’, Heliothis armigera entomopoxvirus ‘L’, Locusta migratoria entomopoxvirus 'O', Oedaleus senigalensis entomopoxvirus 'O', Operophtera brumata entomopoxvirus 'L', Schistocera gregaria entomopoxvirus 'O'. 11. Gammaentomopoxvirus: Aedes aegypti entomopoxvirus, Camptochironomus tentans entomopoxvirus, Chironomus attenuatus entomopoxvirus, Chironomus luridus entomopoxvirus, Chironomus plumosus entomopoxvirus, Goeldichironomus haloprasimus entomopoxvirus. There are many other poxviruses which are not assigned to a particular genus: Diachasmimorpha entomopoxvirus, Skunkpox virus, Uasin Gishu disease virus, Auzduk disease virus, Camel contagious ecthyma virus, Chamois contagious ecthyma virus, Sealpox virus, Crowpox virus, Peacockpox virus, Penguinpox virus, California harbor seal poxvirus, Cotia virus, Dolphin poxvirus, Embu virus, Grey kangaroo poxvirus, Marmosetpox virus, Molluscum-like poxvirus, Mule deer poxvirus, Nile crocodile poxvirus, Quokka poxvirus, Red kangaroo poxvirus, Salanga poxvirus, Spectacled caiman poxvirus, and Yoka poxvirus.
The paramyxoviruses (single stranded, negative sense) are divided into 7 genera: 1. Rubulavirus: Human parainfluenza virus 2, Human parainfluenza virus 4 (includes several different strains), Mapuera virus, Mumps virus, Porcine rubulavirus, Simian virus 5, Simian virus 41. 2. Avulavirus: Avian paramyxovirus 2, Avian paramyxovirus 3, Avian paramyxovirus 4, Avian paramyxovirus 5, Avian paramyxovirus 6, Avian paramyxovirus 7, Avian paramyxovirus 8, Avian paramyxovirus 9, Newcastle disease virus. 3. Respirovirus: Bovine parainfluenza virus 3, Human parainfluenza virus 1, Human parainfluenza virus 3, Sendai virus, Simian virus 10. 4. Henipavirus: Hendra virus, Nipah virus. 5. Morbillivirus: Canine distemper virus, Cetacean morbillivirus virus, Measles virus, Peste-des-petits-ruminants virus, Phocine distemper virus, Rinderpest virus. 6. Pneumovirus: Bovine respiratory syncytial virus, Human respiratory syncytial virus, Murine pneumonia virus. 7. Metapneumovirus: Avian metapneumovirus, Human metapneumovirus. There are also some unassigned viruses in this family: Tupaia paramyxovirus, Fer-de-Lance virus, Menangle virus, Nariva virus and Tioman virus.
Even a viral agent against a family such as the Arenaviridae or the Bunyaviridae is unknown; these viruses are simply too diverse. Because of the great diversity of these viruses, which arises in part due to the wide range of mammals and birds that these infect, for a compound to work generally against these is contrary to present medical knowledge. Indeed, there is presently no agent which is effective against even a modest range of pox viruses. Currently, the only marketed antiviral that has inhibitory effects on any poxvirus is Cidofovir, which, however, as of yet has not been established as effective for the treatment of any pox disease. The vast majority of both DNA and RNA viruses have no effective antiviral treatment. Schickli et al. (“Challenges in developing a pediatric RSV vaccine”) state “There is currently no approved RSV vaccine, and the goal of preventing RSV-associated illness in the general population remains unmet.”
Thus, the art of developing and testing drugs, particularly for use in treating any viral or bacterial infection, is extremely unpredictable.
2. The breadth of the claims
Claims 1-7 and 13-20 are very broad in terms of the type of diseases being treated: all types of microbial infections are claimed to be prevented or treated with mycolactone.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides examples for treating SARS-CoV-2 in vitro by blocking the Sec61 translocon, thereby blocking virus production. However, the specification does not provide any data that shows that mycolactone is useful for treating any viral infection nor any microbial infection more broadly. In particular, the specification is silent to the treatment of bacterial and fungal infections. Moreover, the specification does not provide any data that shows that mycolactone is useful for preventing any viral infection.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that mycolactone could be predictably used as prevention or treatment for all microbial infections other than SARS-CoV-2 virus.
Determining if a particular compound will treat any particular disease state would require formulation into a dosage form, and subjecting into clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the inventions of claims 1-6 and 8-20 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
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.
Claim 11 recites the limitation "The method of claim 10, wherein the flavivirus is Ebola virus" in line 1. There is insufficient antecedent basis for this limitation in the claim because claim 10 recites a filovirus, not a flavivirus. For examination purposes, the claim will be interpreted as reciting “wherein the filovirus is Ebola virus”.
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, 8-9, and 14-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Demangel (“Immunity against Mycobacterium ulcerans: The subversive role of mycolactone”, cited in the IDS dated 02/28/2024).
Regarding these claims, Demangel teaches the use of mycolactone to treat or prevent Zika virus infection in a subject (p. 217, col. 1, para. 4, “Inhibiting Sec61 with mycolactone in Zika virus–infected cells blocked vacuole formation and virus production. It significantly delayed virus propagation and lethality in IFNAR−/− mice (personal communication)”). Delaying virus propagation and lethality counts as preventing the disease as per the instant specification (para. 0031, “Preventing or prevention refers to delaying or forestalling the onset, development, or progression of a microbial condition or disease for a period”).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Eke (“Targeting the Sec61 translocon to inhibit SARS-CoV-2 replication”) in view of Wong (“Inflammation in COVID-19: from pathogenesis to treatment”) and Small et al. (US Patent 6,680,055 B1).
Eke teaches the use of mycolactone to treat SARS-CoV-2 infection in vitro by inhibiting the Sec61 translocon, thereby inhibiting virus production (abstract). Eke does not teach the use of mycolactone to treat SARS-CoV-2 infection in a subject, nor the role of inflammation in SARS-CoV-2 infection or the use of mycolactone to inhibit inflammation.
Wong teaches that inflammation is implicated in the pathogenesis of COVID-19, the disease caused by SARS-CoV-2 infection (pg. 1, col. 2, “One of the key features of COVID-19 is the over-whelming inflammation observed in some patients, especially those who develop severe illness. An exaggerated immune response mediated by an array of cytokines plays a role in the pathogenesis of the disease. Studies have demonstrated that several types of immune cells and inflammatory mediators are involved in the disease process. Hence researchers from all over the world have explored several anti-inflammatory and other pharmacotherapeutic agents to combat the deadly inflammation”). Wong does not teach the use of mycolactone to inhibit inflammation.
Small et al. teaches the use of mycolactone in a subject to inhibit inflammation (col. 12, para. 3, “This example shows that mycolactone and other polyketide macrolides of the present invention are potent anti-inflammatory agents”).
It would have been obvious to one of ordinary skill in the art before the effective filing date to administer mycolactone to a subject to treat SARS-CoV-2 infection because at the time the invention was made, it was known that mycolactone is effective for treating SARS-CoV-2 infection in vitro as clearly taught by Eke. It would have been obvious to modify the teaching of Eke to provide the instantly claimed invention because Wong teaches that inflammation is implicated in COVID-19 infection and Small et al. teaches both that mycolactone inhibits inflammation and is safe to administer in vivo, which would render mycolactone safe and effective for in vivo administration to treat COVID-19 infection. One would have been motivated and had a reasonable expectation of success in doing so given the teaching by Eke that mycolactone treats SARS-CoV-2 in vitro, the teaching by Wong that inflammation is implicated in the pathogenesis of COVID-19, and the teaching by Small that mycolactone suppresses inflammation and is safe to administer in vivo. Thus, claims 1-7 are rejected.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Dhungel et al. (“Responses to chemical cross-talk between the Mycobacterium ulcerans toxin, mycolactone, and Staphylococcus aureus”) teaches the in vitro effects of mycolactone on Staphylococcus aureus growth and metabolism, but does not teach the use of mycolactone to treat S. aureus in a subject.
Pohl et al. (“Sec61 Inhibitor Apratoxin S4 Potently Inhibits SARS-CoV-2 and Exhibits Broad-Spectrum Antiviral Activity”) teaches the use of apratoxin S4 to treat SARS-CoV-2, influenza A, Zika virus, West Nile virus, and Dengue virus in vitro (abstract; also pg. 1268, para. 3, “Apra S4 also showed potent antiviral activity in the low nM range”), using the same mechanism of Sec61 inhibition for which mycolactone is used in the instant disclosure. However, in vivo results and efficacy are not discussed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLIVER D. HEES whose telephone number is (571)272-9840. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, AMY L. CLARK can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/OLIVER D HEES/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628