Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claim Status
Claims 1-20 are currently pending. There are no currently new, amended or canceled claims. Claims 1-20 will be examined on the merits herein.
Priority
The application 19/085,932 filed on September 21, 2023 claims priority from Provisional 63/409,491 of PCT/US2023/074756 filed on September 23, 2022.
Information Disclosure Statement (IDS)
Accordingly, the information disclosure statement is being considered by the examiner.
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.
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 2-9 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.
Claim 2 recites “wherein the peptide contains a serine (S) amino acid residue at least at positions 47 and 77 of the amino acid sequence”. The recitation is interpretated as serine amino acid residues can be in other positions of the sequence. However, it is uncertain what is the position of the other serine amino acid residues in the sequence. Therefore, claim 2 is indefinite.
Claim 5 recites the “a method of eliciting an immune response in a subject”. However, the claim fails to define “a subject”. Even though, the specification discloses the subject is a mammal or a human (human patient), the term “a subject” is indefinite because there is no boundary for the term “a subject” in the claim. Therefore, claim 5 is indefinite.
Claims 6-7 recite “the subject”. However, the claims fail to define “the subject”. Claims 6, 7 recites “a fungal disease” and “a symptom thereof”. However, it is unclear which fungal disease and symptom thereof can be treated or protected by the method. Therefore, the claims are indefinite.
Claim 7 also recites “an isolated or purified antibody or an antigen-binding fragment or an isolated antiserum comprising an antibody, or an antigen-binding fragment thereof, that specifically binds an immunogenic peptide of claim 1”. However, the claim fails to define the particular antibody. Therefore, the claim is indefinite.
Claims 8-17 are rejected as they depend from rejected claim 7, yet fail to resolve the issues of particularly point out and distinctly claim the subject matter.
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 10, 12-17 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. This is a written description rejection.
The instant claims are drawn to the a method of treating or protecting a subject against disease, or a symptom thereof associated with or caused by a fungal infection, wherein the disease, or a symptom thereof, is selected from pulmonary disease, asthma, severe asthma, refractory asthma, Chronic Obstructive Pulmonary Disease (COPD), chronic bronchitis, pneumonia, Pneumocystis pneumonia, bronchiectasis, aspergillosis, Invasive Pulmonary Aspergillosis (IPA), vaginitis, urinary tract infections (UTIs), organ transplant, tissue transplant, immunodeficiency disease, HIV, AIDS, HIV/AIDS, congenital disease, autoimmune disease, rheumatoid arthritis, psoriasis, inflammation-related disesase, diabetes, Type 1 diabetes, or Type 2 diabetes, the method wherein the Aspergillus-associated disease is aspergillosis or Invasive Pulmonary Aspergillosis (IPA) and/or symptoms thereof, the method wherein the subject is immunocompromised or immunosuppressed. The method wherein the immunocompromised or immunosuppressed subject is a pre-transplant subject or a post-transplant subject. The method wherein the immunocompromised or immunosuppressed subject is being treated for cancer, an immunodeficiency disease, a congenital disease, or an autoimmune disease. The method wherein the immunocompromised or immunosuppressed subject is being treated for HIV, AIDS, HIV/AIDS, rheumatoid arthritis, or psoriasis. The method wherein the subject is a human.
The claims encompass diseases, and symptoms thereof associated with or said to be caused by a fungal infection, however the specification does not teach the treatment of all forms/types of diseases, and symptoms said to be treatable by the applicant’s method. Also, the specification does not teach that any subject can be protected against disease, or a symptom thereof associated with or caused by a fungal infection by the applicant’s method. The applicability of the method to all types of diseases, and symptoms and subjects asserted in the claims mentioned above is unknown and/or not readily reproducible by the artesian.
In the specifications, the applicant disclaims Figures 1-3 and provides results regarding experimental data obtained by using mouse model. The specifications teaches that “FIG. 1 illustrates a graph showing that the PF.KEX2b immunogen generated an antibody response and the production of antibodies as measured by antibody titer in plasma of animals (mice) that had received the PF-KEX2b immunogen. The results present the mean plasma anti-PF.KEX2b-specific immunoglobulin G (IgG antibody) reciprocal endpoint titer (RET), as determined by enzyme-linked immunosorbent assay (ELISA), following three immunizations of the mice with either 10 pg (represented by "x" markings on graph) or 20 pg10 (represted by solid black circles on graph) of the PF.KEX2b immunogen and alum (ALHYDROGEL®; InvivoGen, San Diego, CA) adjuvant. Time points of immunization of the animals are indicated by arrows on the graph. "Wpv": weeks post-vaccination”.
The specification also teaches that “FIGS. 2A and 2B present a study design diagram and a graph showing survival curves related to a fungal challenge study of invasive pulmonary aspergillosis in an immunosuppression mouse model. FIG. 2A presents the design of the fungal challenge study in animals. FIG. 2B shows a survival curve of animals immunized with the PF.KEX2b peptide immunogen (represented by "x" markings on graph), compared to sham-immunized control animals. The PF.KEX2b-immunized animals were significantly protected from developing aspergillosis disease following immunosuppression (elicited using tacrolimus and hydrocortisone), compared to the sham-immunized controls (*p=0.0323, by Mantel-Cox test). The results demonstrated that immunosuppressed animals immunized with the PF.KEX2b peptide immunogen in conjunction with an adjuvant (ALHYDROGEL®) had a significant reduction in mortality related to Aspergillus fungal infection compared to sham- immunized control animals (p=0.0323). FIGS. 3A and 3B show Coomassie stained gels and western blot analyses of PF- KEX2a peptide (i.e., Pan-fungal peptide 2; see, e.g., US Pub. No. 2022/0184190, the contents of which are incorporated by reference herein) and the PF-KEX2b peptide described herein. FIG. 3A: PF-KEX2a protein quality analysis prior to use in immunization/vaccination of animals and following prolonged storage at -80C. Following overnight dialysis of the PF- KEX2a peptide in PBS, the dialyzed protein was frozen in several aliquots for in vivo use at later timepoints”. “The quality of the protein was assessed by Coomassie staining following gel electrophoresis and PF-KEX2a immunoblot analysis immediately following dialysis (left panel) and PF-KEX2b immunoblot analysis (right panel) following dialysis and storage at -80°C”.
However, there is also uncertainty regarding to the use of the method for the fungal disease associated with or caused by any disease mentioned above. Thus, one of skill in the art would not readily recognize the use of the method to treat or protect a subject against all types of diseases and symptoms associated with/or caused by the fungal infections claimed by the applicant if there is a lack of written description of method and use of the genus (types/forms of diseases and symptoms) in the claims. The written description requirement is not fulfilled by the applicant.
In order to comply with the written description requirement, the applicant must fully disclosure all types of diseases or symptoms thereof associated with or caused by a fungal infection claimed to be treatable and/or not developed by the applicant’s invention regarding the protocol of use of the method for all forms/types of diseases and symptoms associated with or caused by fungus infections in specifications.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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 Applicants were in possession of the claimed genus.
Thus, the method recited in claims 10, 12-17 must be able to treat and/or protect any the fungal disease associated with or caused by any disease mentioned above recited in claims. It is apparent that there is no written description in the specification showing that the method comprising the administration of claimed polypeptides(s) of claims 1-2 is capable of treating or protecting each of the fungal diseases claimed in the invention. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim. In the specification, there is no clear disclosure of each fungal diseases associated with or caused by have been treated or controlled using the method claimed in the invention. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
The only mention of protection against a disease or symptom associated with or caused by a fungal disease is regarding to “the PF.KEX2b-immunized animals that were significantly protected from developing aspergillosis disease following immunosuppression (elicited using tacrolimus and hydrocortisone” (see specifications); thus, the skilled artesian cannot envision the detailed method of treating or protecting any of the diseases associated with or caused fungus infections. Mohd et al. (Mohd Sazlly Lim S, Sinnollareddy M, Sime FB. Challenges in Antifungal Therapy in Diabetes Mellitus. J Clin Med. 2020 Sep 6;9(9):2878. doi: 10.3390/jcm9092878) teaches that diabetic patients have an increased propensity to Candida sp. infections due to disease-related immunosuppression and various other physiological alterations. The incidence of candidiasis has increased in number over the years and is linked to significant morbidity and mortality in critically ill and immunosuppressed patients. Treatment of infection in diabetic patients may be complicated due to the various disease-related changes to the pharmacokinetics and pharmacodynamics (PK/PD) of a drug, including antifungal agents. Application of PK/PD principles may be a sensible option to optimise antifungal dosing regimens in this group of patients. Further studies on PK/PD of antifungals in patients with diabetes mellitus are needed as current data is limited or unavailable. High mortality rates have been reported for patients with Candida sp. infection, particularly in those with Candida sp. bloodstream infection. Barchiesi et al. for example, reported a mortality rate of 28–45% in patients with candidaemia. Similarly, in an earlier study of candidaemia in immunocompromised patients, the mortality rates associated with C. krusei and C. albicans were 49% and 28%, respectively. Therefore, adequate treatment is of tremendous importance in this group of patients. However, treatment of infection in a diabetic patient is not as straight forward as those without diabetes mellitus.
Further, Gamaletsou et al. (Gamaletsou MN, Rammaert B, Bueno MA, Sipsas NV, Moriyama B, Kontoyiannis DP, Roilides E, Zeller V, Taj-Aldeen SJ, Henry M, Petraitis V, Denning DW, Lortholary O, Walsh TJ; International Osteoarticular Mycoses Consortium. Aspergillus arthritis: analysis of clinical manifestations, diagnosis, and treatment of 31 reported cases. Med Mycol. 2017 Apr 1;55(3):246-254. doi:10.1093/mmy/myw077) teaches that Aspergillus arthritis and the more commonly encountered Candida arthritis are frequently caused by hematogenous dissemination to the joints. Notably, some immunocompromised patients did not have an apparent pulmonary or extra-osseous focus, suggesting that isolated Aspergillus arthritis may arise de novo in immunosuppressed hosts without prior antifungal therapy. In comparison to Candida arthritis, Aspergillus arthritis may be more frequently associated with direct inoculation in immunocompetent patients possibly as the result of an environmental contamination during trauma or surgery. This pathogenesis is shared by non-Aspergillus mould osteoarticular infections, where direct inoculation occurred in 54.5% of cases. In contrast, such cases of direct inoculation in Candida arthritis are unusual. Most cases of Aspergillus and Candida arthritis arise de novo before the initiation of antifungal therapy. However, approximately one-third of cases of Candida arthritis emerges as breakthrough infection while receiving antifungal therapy. “Overall survival was 65%. Aspergillus arthritis mainly develops as a de novo infection involving knees and intervertebral disks in immunocompromised patients with localizing symptoms. Contiguous osteomyelitis is frequently observed. Diagnosis is established by synovial fluid culture. Aspergillus arthritis is therapeutically challenging with most patients undergoing surgery and protracted antifungal therapy”.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc., 107 F.3d 1565, 1572, 41 USPQ2dl961,1966 (1997); In re Gosteli, 872 F.2dl008,1012,10 USPQ2dl614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d.
Therefore, neither the art nor the specification provide a representative number of diseases and or symptoms associated with or caused by fungal infections that can be treated or not developed by the invention.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
In order to comply with the written description requirement, the applicant needs provide with the methods claimed to all the diseases and symptoms thereof, and subjects in specifications.
Therefore, claims 10, 12-17 are rejected for failing to comply with the written description requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Norris1 et al. (US 9914917 B1: hereafter Norris1; PTO-892) in view of Norris2 et al. (WO 2020154510 A1; hereafter Norris2; PTO-892).
‘917 teaches “a vector comprising a polynucleotide encoding a peptide consisting of the amino acid sequence DDDGKTVDGP SSLVLRALIN GVNNGRNGLG SIYVFASGNG GIYEDNCNFD GYANSVFTITIGGIDK HGKRLKYSEA CSSQLAVTYAG GSA (SEQ ID NO: 1)”, which is pertinent to claim 1, 19. See for example, claim 1.
‘917 teaches polypeptide of SEQ ID NO:1. The SEQ ID NO:1 of Norris matches 92.8% of SEQ ID NO:1, which is pertinent to claim 1, 19. See for example, claim 1. See Figure below.
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‘917 teaches “a method for immunizing a mammal, including a human being, against a pathogenic fungus such as Pneumocystis, comprising administering to the mammal an effective amount of a vaccine a nucleic acid, a polypeptide, a vector, or a cell as described. A further embodiment comprises a pharmaceutical composition that comprises an immunologically reactive amount of at least one member selected from the group consisting of: a) the mini-Kexin polypeptide, or an immunogenic portion thereof; (b) a polypeptide whose amino acid sequence has an identity of at least 70%, 75%, 80%, 85%, 90%, or 95% to anyone of said polypeptides in Cal; and is immunogenic; (c) a fusion polypeptide comprising at least one polypeptide according to (a) or (b) and at least one fusion partner; d) a nucleic acid that encodes a polypeptide according to Cal, (b) or (c); (e) a nucleic acid whose sequence is complementary to the sequence of a nucleic acid according to (d); (f) a nucleic acid sequence having a length of at least 10 nucleotides, or at least 20 nucleotides, that hybridizes under stringent conditions with a nucleic acid according to (d) or (e); and (g) a non-pathogenic micro-organism that has incorporated therein (e.g. placed in a plasmid or chromosome) a nucleic acid sequence according to (d), (e), or (f) in a manner to permit expression of the encoded polypeptide”, which is pertinent to claim 1-2, 5-6, 19. See for example, column 7; lines 43-65, column 7; lines 67, column 8; lines 1-23.
‘917 teaches “preferred minimum percentage of sequence identity is at least 80%, such as at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, and at least 99.5%”, which is pertinent to claims 1-2, 19.
‘917 teaches “Variants.” “A common feature of the polypeptides of the invention is their capability to induce an immunological response. It is understood that a variant of mini-Kexin produced by substitution, insertion, addition or deletion may also be immunogenic as determined by any of the assays described herein”, which is pertinent to claim 1-2, 19. See for example, column 9; lines 44-54.
‘917 teaches that “each polypeptide may thus be characterized by specific amino acids and be encoded by specific nucleic acid sequences. It will be understood that such sequences include analogues and variants produced by recombinant or synthetic methods wherein such polypeptide sequences have been modified by substitution, insertion, addition or deletion of one or more amino acid residues in the recombinant polypeptide and are still immunogenic. Substitutions are preferably conservative”, which is pertinent to claims 1-3, 19, 20. See for example, column 8; lines 29-51.
‘917 teaches A “substantially pure polypeptide fragment” means a polypeptide preparation that contains at most 5% by weight of other polypeptide material (lower percentages of other polypeptide material are preferred, e.g. at most 4%, at most 3%, at most 2%, at most 1%, and at most ½%). It is preferred that the substantially pure polypeptide is at least 96% pure, i.e. that the specified polypeptide constitutes at least 96% by weight of total polypeptide material present in the preparation, and higher percentages are preferred, such as at least 97%, at least 98%, at least 99%, at least 99.25%, at least 99.5%, and at least 99.75%. It is especially preferred that the polypeptide fragment is in “essentially pure form”, i.e. that the polypeptide fragment is essentially free of any other antigen with which it is natively associated, i.e. essentially free of any other antigen from the same fungus. This can be accomplished by preparing the polypeptide fragment by means of recombinant methods in a non-fungal host cell, or by synthesizing the polypeptide fragment by the well-known methods of solid or liquid phase peptide synthesis, e.g. by the method described by Merrifield or variations thereof, which is pertinent to claim 3, 20. See for example, column 8, lines 52-66, column 9, lines 1-5.
‘917 teaches “a method of inducing an immune response in a subject, the method comprising administering to the subject an effective amount of a composition comprising a vector comprising a polynucleotide encoding a peptide consisting of the amino acid sequence DDDGKTVDGP SSLVLRALIN GVNNGRNGLG SIYVFASGNG GIYEDNCNFD GYANSVFTITIGGIDK HGKRLKYSEA CSSQLAVTYAG GSA (SEQ ID NO: 1) and a pharmaceutically acceptable excipient”, which is pertinent to claims 1, 4-6, 19-20. See for example, claim 4.
‘917 teaches “proteins derived from Kexin, nucleic acids encoding those proteins, and the use of the proteins or nucleic acids as vaccines, for example, as vaccines against Pneumocystis jirovecii or other Pneumocystis subspecies (spp.)”, which is pertinent to claims 4-5, 19-20. See for example, see column 1; lines 41-45.
‘917 teaches that “Pneumocystis is a genus of fungi that is found in the respiratory tracts of many mammals and humans Pneumocystis infection is easily defended by a healthy immune system. The symptoms of PCP infection include pneumonia, fever, and respiratory symptoms such as dry cough, chest pain and dyspnea”. PCP infection will occur in approximately 15%-28% of individuals with AIDS in a given year. Within the population of HIV/A1DS patients with PCP, the mortality rate is between 10%-20%. “A vaccine is disclosed that promotes CD4+ T cell-independent host defense mechanisms to defend against infection by fungi such as Pneumocystis subspecies (spp.). The vaccine may be used to prevent or to treat fungal infections. The novel vaccine can provide protective immunity, even for immunocompromised individuals such as HIV patients having reduced levels of CD4+ T cells”, which is pertinent to claim 6, 13-17, 19-20. See for example, See abstract.
‘917 teaches that “Organ transplant recipients are also at risk for Pneumocystis (PCP) infection. Transplant recipients take regimens of anti-rejection drugs that function by suppressing the immune system. The overall incidence of PCP in solid organ transplant recipients not taking PCP prophylaxis is about 5%, with the highest incidence following liver, heart, and lung transplants”, which is pertinent to claim 13-14, 17.
‘917 teaches “The method of claim 4, wherein the immune response is sufficient to prevent or treat a disease caused by Pneumocystis infection in the subject”, which is pertinent to claims 6, 13-20. See for example, See claim 5, 13-17.
‘917 teaches “passive transfer experiments into scid mice using control serum, serum from Kexin/CD40L vaccinated mice, and serum from vaccinated mice that had been pre-adsorbed against recombinant Kexin. The mice were then challenged with Pneumocystis (2×IOS cysts) intratracheally. Mice were sacrificed at day 28, and PC burden in the lung was assessed by real-time PCR. Transfer of 300 μl of serum from Kexin/CD40L-vaccinated mice resulted in significantly reduced Pneumocystis burden as compared to control serum. Adsorption of serum against recombinant Kexin significantly attenuated the protection of the transferred serum”, which is pertinent to claims 6--11. See for example, Example 9, column 14; lines 49-61.
However, ‘917 does not teach the Aspergillus-associated disease is aspergillosis or Invasive Pulmonary Aspergillosis (IPA) and/or symptoms thereof as claim 12.
‘917 does not teach explicitly teach a vaccine comprising an effective amount of PF-KEX2b peptide of SEQ ID NO: 2 or a polynucleotide encoding PF-KEX2b as claim 18.
‘510 teaches “the method of claim 11, wherein the pulmonary disease or pulmonary dysfunction is aspergillosis or Invasive Pulmonary Aspergillosis (IPA), which is pertinent to claim 12. See for example, claim 13.
‘510 teaches methods for treating or preventing infection (e.g., opportunistic infection) by fungal pathogens, as well as treating or preventing pulmonary disease and poor pulmonary function associated with infection by fungal pathogens, which is pertinent to claim 18. See for example Summary, page 1; lines 26-28.
‘510 teaches an immunogenic peptide or a polynucleotide encoding an immunogenic peptide having at least about 95% or greater amino acid sequence identity to SEQ ID NO: 2, which is pertinent to claims 1, 18. See for example, Summary; page 1; lines 29-32.
‘510 teaches SEQ ID NO: 2 (Pan-fungal peptide 2), or fragments thereof. The SEQ ID NO: 2 of ‘510 is 97.8% identical to SEQ ID NO: 2, which is pertinent to claims 1, 18. See Figure below.
‘510 also teaches immunogenic compositions comprising a non-naturally occurring pan-fungal Kex peptide, and methods of using such compositions for the treatment or prevention of infection and/or diseases associated with fungal pathogens (e.g., Pneumocystis, Aspergillus, Candida, or Cryptococcus) in the subject. Also provided are compositions and kits for detecting or quantifying the presence of antibodies directed against a non-naturally occurring pan-fungal Kex peptide in a subject, which is pertinent to claims 7-8. See for example, abstract.
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‘510 teaches SEQ ID NO: 1 (Pan-fungal peptide 1), or fragments thereof. The SEQ ID NO: 1 of ‘510 (Norris1) is 97.8% identical to SEQ ID NO: 1. See Figure below.
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‘510 teaches that “By “Pan-fungal peptide 1”and “Pan-fungal peptide 2” is meant a KEX peptide comprising a sequence having 95, 96, 97, 98, 99, or 100% identity to the amino acid sequence of Pan-fungal peptide 1 and having immunogenic activity. In some embodiments, a Pan-fungal peptide 1 and/ or a Pan-fungal peptide 2 comprise 1, 2, or 3 additional amino acids at the carboxy and/or amino terminus of the peptide, which additional amino acids do not alter the peptide’s ability to stimulate an immune response in a subject, which is relevant to claims 1, 5-20. See for example, page 5; lines 15-31.
It is noted that SEQ ID NO: 1 of US 9914917 B1 is at least 70% identical to SEQ ID NO: 2 of WO 2020154510 A1, which is pertinent to claim 1. See Figure below.
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Therefore, it would have been obvious to one of ordinary skill in the art to modify the teachings of ‘917 and ‘510 and thereby arriving at the invention of claim 1-20, because SEQ ID NO: 1 of ‘917 encodes mini-Kexin protein, which can be used in a method for immunizing a mammal, including a human being, against a pathogenic fungus, such as Pneumocystis as taught by ‘917. Also, 917’ teaches that variants of mini-kexin are required to be at least 70% identical to SEQ ID NO: 1 to be immunologically reactive as taught by ‘917. Indeed, the SEQ ID NO: 1 of ‘917 is at least 70% identical to SEQ ID NO: 2 of ‘510. See alignment above (figure). Thus, it would be very desirable and an advantage to modify the SEQ ID NO: 1 of ‘917 to generate new variants of the mini-Kexin, such as SEQ ID NOs: 1-2 of ‘917 for the treatment and protection and diagnostic of infection and disease associated with different fungal pathogens as taught by 917’ and ‘510, it would been obvious to substitute these known equivalents; MPEP 2144.06.
See MPEP 2144(II): “The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art … that some advantage or expected beneficial result would have been produced by their combination.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.
Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PRICILA HAUK TEODORO whose telephone number is (571)272-2784. The examiner can normally be reached M-F 6:15AM-3:00PM.
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, Heather Calamita can be reached at (571) 272-2876. 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.
/PRICILA NMN HAUK TEODORO/Examiner, Art Unit 1645
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
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