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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11 May 2026 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 11 May 2026.
CLAIMS UNDER EXAMINATION
Claims 1, 4-7, 9-10, 14-18 and 21-23 are pending and have been examined on their merits.
PRIORITY
Foreign Priority document EP17195324.3 filed on 06 October 2017 is acknowledged.
REJECTIONS
Claim Rejections - 35 USC § 112
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, 4-7, 9-10, 14-17 and 21 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 claims contain 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 is directed to a method for treating cancer in a subject in need thereof. The claim encompasses any type of cancer. The claim requires administering an endolysin specific for S. aureus to treat cancer in a patient. The claim does not require the patient be infected with S. aureus. The specification provides support for treating cancer in a subject with an S. aureus infection (see page 2, lines 6-7). The specification teaches “any type of cancer where oncogenic bacteria are associated with pathogenesis or oncogenesis of the cancer” (see page 3, lines 36-40).
Claim 1 encompasses T cell-leukemia. T-cell leukemia/lymphoma is a rare malignancy associated with the human retrovirus human T-cell lymphotropic virus type 1 (emphasis added; Graham et al. Adult T-cell leukemia/lymphoma. Proc (Bayl Univ Med Cent). 2014 Jul;27(3):235-8). While the specification provides support for treating cancer in a subject with S. aureus, it does not provide support for treating cancer in a subject without an S. aureus infection including those caused by retrovirus. Claims 7 and 16-17 encompass any mucosa associated cancer, including melanoma. It is well known that melanoma arises from melanocytes. The specification does not provide support for treating all mucosa cancers where S. aureus is not associated with said caner.
Claim 21 is directed to a method to take away the selective advantage of malignant T-cells to proliferate in a subject in need thereof suffering from cancer. The claim encompasses any type of cancer with malignant T cells. The claim requires administering an endolysin specific for S. aureus to treat cancer in a patient. The claim does not require the patient be infected with S. aureus. The specification provides support for treating cancer in a subject with an S. aureus infection (see page 2, lines 6-7). The specification teaches “any type of caner where oncogenic bacteria are associated with pathogenesis or oncogenesis of the cancer” (see page 3, lines 36-40).
T-cell leukemia/lymphoma is a rare malignancy associated with the human retrovirus human T-cell lymphotropic virus type 1 (Graham et al. Adult T-cell leukemia/lymphoma. Proc (Bayl Univ Med Cent). 2014 Jul;27(3):235-8). While the specification provides support for treating cancer in a subject with S. aureus, it does not provide support for treating cancer in a subject without an S. aureus infection.
A consideration of the four corners of the specification does not reflect that applicants have actually invented the claimed invention, since the specification lacks adequate written description for treating all cancers encompassed by the claims. Dependent claims 4-7, 9-10 and 14-17 are included in this rejection because they encompass cancer not associated with S. aureus infection.
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 5 and 22-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 recites the endolysin is selected from the group consisting of the endolysins “depicted as set forth in SEQ ID NO:19 to SEQ ID NO:74”. It is unclear what Applicant means by “depicted as”. It is unclear what percent sequence identity the Applicant intends to claim. The metes and bounds of the claim are unclear. Appropriate correction is required.
Claim 22 recites “CTCL T-cells”. “CTCL” is an abbreviation for “cutaneous T-cell lymphoma”. It is unclear if the claim is referring to specific T cells in a patient with cutaneous T-cell lymphoma. The metes and bounds of the claim are unclear. Appropriate correction is required.
Claim 23 recites “CTCL T-cell-specific CD8 cytotoxic T cells”. The claim language is unclear. “CTCL” is an abbreviation for “cutaneous T-cell lymphoma”. It is unclear if the claim is referring to specific CD8 T cells in a patient with cutaneous T-cell lymphoma. It is unclear what the Applicant means by “T-cell-specific CD8 cytotoxic T cells”. The metes and bounds of the claim are unclear. Appropriate correction is required.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 4-7, 9-10, 16-18 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Willerslev-Olsen et al. (previously cited; Bacterial Toxins Fuel Disease Progression in Cutaneous T-Cell Lymphoma. Toxins (Basel). 2013 Aug; 5(8): 1402–1421) in view of Loessner et al. (previously cited; Polypeptide mixes with antibacterial activity. US20150118189A1) as evidenced by Berube et al. (Staphylococcus aureus α-Toxin: Nearly a Century of Intrigue. Toxins 2013, 5, 1140-1166) and Rahman et al. (previously cited; Endolysin, a Promising Solution against Antimicrobial Resistance. Antibiotics 2021, 10, 1277 pages 123).
Willerslev-Olsen teaches bacterial infections constitute a major clinical problem caused by compromised skin barrier and a progressive immunodeficiency in patients with cutaneous T-cell lymphoma (CTCL). The majority of patients with advanced disease die from infections with bacteria, including Staphylococcus aureus (Abstract). Staphylococcus aureus is a major source of morbidity in CTCL causing chronic or recurrent skin infections and life-threatening systemic infections such as sepsis, pneumonia and intra-abdominal infections (see page 1408, last paragraph). The art teaches elimination of S. aureus infection with antibiotics was associated with a rapid clinical improvement: in some patients treatment resulted in complete clinical response with no residual skin involvement by CTCL (see page 1412, second paragraph).
The art also teaches the following:
Bacterial toxins such as staphylococcal enterotoxins (SE) have long been suspected to be involved in the pathogenesis in CTCL (Abstract). S. aureus is renowned for its ability to produce staphylococcal enterotoxins (SE) (also known as superantigens). Superantigens are characterized by their ability to activate T lymphocytes (page 1408, last paragraph). As evidenced by Berube et al., Staphylococcus aureus secretes α-toxin (see Abstract, first sentence of page 1141). Therefore the patient with S. aureus taught by the art produces an alpha toxin which inherently has the characteristics recited in claim 1.
Willerslev-Olsen teaches administration of antibiotics able to treat S. aureus (an oncogenic bacterium) infection in patients with CTCL. The art does not teach administration of an endolysin specific for S. aureus.
Loessner teaches a composition used as an antimicrobial agent (Abstract). The art teaches a medical composition for the treatment of a condition related to Staphylococcus ([0136]). The art teaches a composition for treating an infectious disease caused by the species S. aureus. The infectious disease is preferably a skin infection ([0136]).
Loessner teaches the invention relates to a polypeptide which exhibits a lytic activity of at least 30, 40, 50, 60, 70, 80,90, 100, 150 or 200% or more of a lytic activity of S. aureus bacteriophage d2638a endolysin (Ply2638 endolysin identified by SEQID NO: 2) encoded by SEQID NO: 1 (see [0010]). The polypeptide comprises an endolysin ([0107]). As evidenced by Rahman et al., endolysins are a class of antibiotics (see page 2, second paragraph, lines 4-5).
It would have been obvious to try treating CTCL in a patient by administering an endolysin specific for Staphylococcus aureus. One would have been motivated to do so since Willerslev-Olsen teaches CTCL can be improved by treating S. aureus with antibiotic and Loessner teaches an endolysin (an antibiotic) can be used to treat the same bacteria. One would have had a reasonable expectation of success since Loessner teaches the compositions can be used to treat skin infections by S. aureus. One would have expected similar results since both references teach treating skin infections caused by Staphylococcus aureus using antibiotics. Because administration of endolysin is rendered obvious, it would be expected to treat cancer as claimed absent evidence the contrary. Willerslev-Olsen is directed to a cancer patient with S. aureus. As evidenced by Berube (supra), alpha toxin is a protein inherently secreted by S. aureus (supra). Therefore the alpha toxin would have the characteristics recited in claim 1. Therefore claim 1 is rendered obvious.
Loessner teaches the polypeptide is chimeric and heterologous ([0106]). Claim 4 is included in this rejection.
Loessner teaches the following ([0086]):
Also preferred is a combination according to the present invention, wherein a first polypeptide according to the present invention has at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 60, a second polypeptide according to the present invention as at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 72 and a third polypeptide according to the present invention has at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 54.
Therefore the art teaches a composition comprising SEQ ID NO: 72.
SEQ ID 72 cited in Table 2 for artificial construct HXaM23-LST_M23-LST_CWT-NM3 reads on the endolysin SEQ ID 72 of the instant invention (see Table 1).
Therefore claim 5 is included in this rejection.
Willerslev-Olsen is directed to humans and Loessner teaches administration to humans ([0140]). Therefore claim 6 is included in this rejection.
As evidenced by the instant specification, CTCL is a mucosa associated cancer ([0018]). Therefore claim 7 is included in this rejection.
Loessner teaches pharmaceutical acceptable carrier ([0130]). Said carrier is broadly interpreted to be an excipient. Therefore claim 9 is included in this rejection.
Loessner teaches a mixture of endolysins that treat S. aureus. The art teaches the following ([0086]):
Also preferred is a combination according to the present invention, wherein a first polypeptide according to the present invention has at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 60, a second polypeptide according to the present invention as at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 72 and a third polypeptide according to the present invention has at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 54.
The first polypeptide is broadly interpreted to read on a second anti-cancer medicament. Therefore claim 10 is included in this rejection.
As evidenced by the instant specification, CTCL is a mucosa associated cancer ([0018]). Therefore claims 16-18 are included in this rejection.
Regarding claim 21: The teachings of the Willerslev-Olsen are reiterated.
Willerslev-Olsen teaches administration of antibiotics able to treat S. aureus (an oncogenic bacterium) infection in patients with CTCL. The art does not teach administration of an endolysin specific for S. aureus.
The teachings of Loessner are reiterated.
It would have been to administer an endolysin specific for S. aureus to treat a patient with CTCL. Willerslev-Olsen teaches CTCL can be improved by treating S. aureus with an antibiotic and Loessner teaches an endolysin (an antibiotic) can be used to treat the same bacteria. The skilled artisan would administer an endolysin with lytic activity against S. aureus to treat a condition caused by S. aureus. One would have had a reasonable expectation of success since Loessner teaches the compositions can be used to treat skin infections by S. aureus. One would have expected similar results since both references treat skin infections caused by S. aureus using antibiotics.
Because administering an endolysin specific to S. aureus is rendered obvious, it would be expected to take away the selective advantage of malignant T cells to proliferate as recited in preamble of the claim. Therefore claim 21 is rendered obvious.
Regarding independent claim 22: The teachings of Willerslev-Olsen are reiterated. The art teaches patients with CTCL. The patients have malignant T cells. Willerslev-Olsen teaches administration of antibiotics able to treat S. aureus (an oncogenic bacterium) infection in patients with CTCL. The art does not teach administration of an endolysin specific for S. aureus.
The teachings of Loessner are reiterated.
It would have been to administer an endolysin specific for S. aureus to a patient with CTCL. Willerslev-Olsen teaches CTCL can be improved by treating S. aureus with an antibiotic and Loessner teaches an endolysin (an antibiotic) can be used to treat the same bacteria. The skilled artisan would administer an endolysin with lytic activity against S. aureus to treat a condition caused by S. aureus. One would have had a reasonable expectation of success since Loessner teaches the compositions can be used to treat skin infections by S. aureus. One would have expected similar results since both references treat skin infections caused by S. aureus using antibiotics. Because administering an endolysin specific for S. aureus is rendered obvious, it would be expected to take away the selective advantage of CTCL T cells to proliferate as recited in step b) of the claim. Therefore claim 22 is rendered obvious.
Regarding independent claim 23: The teachings of Willerslev-Olsen are reiterated. The art teaches patients with CTCL. The patients have malignant T cells. Willerslev-Olsen teaches administration of antibiotics able to treat S. aureus (an oncogenic bacterium) infection in patients with CTCL. The art does not teach administration of an endolysin specific for S. aureus.
The teachings of Loessner are reiterated.
It would have been to administer an endolysin specific for S. aureus to a patient with CTCL. Willerslev-Olsen teaches CTCL can be improved by treating S. aureus with an antibiotic and Loessner teaches an endolysin (an antibiotic) can be used to treat the same bacteria. The skilled artisan would administer an endolysin with lytic activity against S. aureus to treat a condition caused by S. aureus. One would have had a reasonable expectation of success since Loessner teaches the compositions can be used to treat skin infections by S. aureus. One would have expected similar results since both references treat skin infections caused by S. aureus using antibiotics. Because administering an endolysin specific for S. aureus is rendered obvious, it would be expected to restore the cytotoxic activity of CTCL T-cell-specific CD8 cytotoxic T-cells as recited in step b) of the claim. Therefore claim 23 is rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 04 May 2026 are acknowledged.
Argument 1: The Applicant argues it has been demonstrated for the first time that the S. aureus alpha-toxin inhibits proliferation of non-malignant T- cells, but not malignant T-cells.
Response to Argument 1: Claim 1 is directed to a method of treating cancer. The arguments are directed to a scientific explanation of the differential effect of S. aureus alpha-toxin on malignant and non-malignant T cells. While claim 1 requires administering an endolysin specific for S. aureus, the subject is not required to have an S. aureus infection or a cancer with malignant T cells. Therefore the argument is not persuasive. Even arguendo the claim did require a cancer in a subject with S. aureus infection, S. aureus inherently secretes alpha toxin (see evidentiary reference). The art is directed to a patient with S. aureus. Therefore it would inherently produce alpha toxin with the claimed characteristics.
Argument 2: The arguments state it was demonstrated for the first time that S. aureus alpha-toxin inhibits cytotoxic activity of CTCL-specific cytotoxic CD8 T cells.
Response to Argument 2: Claim 1 is not directed to CTCL. Regarding claims 22-23: The arguments are directed to a scientific explanation of the effect of S. aureus alpha-toxin on malignant and non-malignant T cells. The claims are directed to a method of treating cancer. Willerslev-Olsen teaches a patient with CTCL. The art teaches S. aureus. As disclosed in the evidentiary reference, S. aureus inherently produces and secretes alpha toxin. Therefore said alpha toxin would be expected to have the characteristics argued by the Applicant.
Argument 3: The Applicant argues the prior art does not teach S. aureus alpha toxin inhibits proliferation of non-malignant T cells, but not malignant T cells. The Applicant argues the prior art does not provide evidence that administration of an endolysin specific for S. aureus effectively treats cancer.
Response to Argument 3: The Applicant’s argument is directed to a scientific explanation effect of S. aureus alpha-toxin on malignant and non-malignant T cells. Claim 1 recites a method of treating cancer. Willerslev-Olsen is directed to CTCL with S. aureus infection (an oncogenic bacteria). As evidenced by Berube, S. aureus inherently produces and secretes alpha toxin. Because S. aureus inherently secretes alpha toxin, the alpha toxin would have the effect argued by the Applicant.
The Loessner reference teaches an endolysin specific for S. aureus (an oncogenic bacteria). The art teaches skin infections caused by S. aureus can be treated with said endolysin.
It would have been to administer an endolysin specific for S. aureus to a patient with CTCL. Willerslev-Olsen teaches CTCL can be improved by treating S. aureus with an antibiotic and Loessner teaches an endolysin (an antibiotic) can be used to treat the same bacteria. The skilled artisan would administer an endolysin with lytic activity against S. aureus to treat a condition caused by S. aureus. One would have had a reasonable expectation of success since Loessner teaches the compositions can be used to treat skin infections by S. aureus. One would have expected similar results since both references treat skin infections caused by S. aureus using antibiotics. Because administering an endolysin specific for S. aureus is rendered obvious, it would be expected to effectively treat as claimed absent evidence to the contrary.
Claims 1, 4-7, 9-10, 14-18 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Nguyen et al. (previously cited; Cutaneous T -cell lymphoma and Staphylococcus aureus colonization. 2008 American Academy of Dermatology 949-952) in view of Loessner et al. as evidenced by Berube et al.
Nguyen teaches Cutaneous T-cell lymphoma (CTCL) is the most common lymphoma of the skin. Infection is a common complication of this disease and is the leading cause of death. The most common pathogen of cutaneous infections and bacteremias in CTCL patients is Staphylococcus aureus (SA). As evidenced by Berube et al., Staphylococcus aureus secretes α-toxin (see Abstract, first sentence of page 1141). Therefore the S. aureus taught by the art produces an alpha toxin that inherently has the characteristics recited in claim 1.
Infection may be in part due to an impaired skin barrier as well as a decrease in the repertoire of normal circulating T cells and immunosuppression. See Background section. Nguyen teaches treating SA colonization and cutaneous infections may help reduce the severity of CTCL (see page 952, left column, first paragraph). It is noted Nguyen teaches MRSA can be found in CTCL patients (Table II).
While the art teaches treating S. aureus infection may help reduce the severity of CTCL, the art does not teach administration of an endolysin specific for S. aureus.
The teachings of Loessner are reiterated.
It would have been obvious to try treating CTCL with an endolysin specific for Staphylococcus aureus. One would have been motivated to do so since Nguyen teaches CTCL can be improved by treating Staphylococcus aureus and Loessner teaches an endolysin can be used to treat the same bacteria. One would have had a reasonable expectation of success since Loessner teaches the compositions can be used to treat skin infections by S. aureus. One would have expected similar results since both references teach treating skin infections caused by Staphylococcus aureus.
Nguyen is directed to a cancer patient with S. aureus. As evidenced by Berube (supra), alpha toxin is a protein inherently secreted by S. aureus (supra). Therefore the alpha toxin would have the characteristics recited in claim 1. Therefore claim 1 is rendered obvious.
Loessner teaches the following ([0086]):
Also preferred is a combination according to the present invention, wherein a first polypeptide according to the present invention has at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 60, a second polypeptide according to the present invention as at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 72 and a third polypeptide according to the present invention has at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 54.
Therefor the art teaches a composition comprising SEQ ID NO: 72.
SEQ ID 72 cited in Table 2 for artificial construct HXaM23-LST_M23-LST_CWT-NM3 reads on SEQ ID 72 of the instant invention (see Table 1).
Therefore claims 4-5 are included in this rejection.
Loessner teaches the endolysin can be administered to humans ([0140]). Therefore claim 6 is included in this rejection.
As evidenced by the instant specification, CTCL is a mucosa associated cancer ([0018]). Therefore claim 7 is included in this rejection.
Loessner teaches pharmaceutical acceptable carrier ([0130]). Said carrier is broadly interpreted to be an excipient. Therefore claim 9 is included in this rejection.
Loessner teaches a mixture of endolysins that treat S. aureus. The art teaches the following ([0086]):
Also preferred is a combination according to the present invention, wherein a first polypeptide according to the present invention has at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 60, a second polypeptide according to the present invention as at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 72 and a third polypeptide according to the present invention has at least 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 100% identity with SEQ ID NO: 54.
The first polypeptide is broadly interpreted to read on a second anti-cancer medicament. Therefore claim 10 is included in this rejection.
It would have been obvious to try treating an antibiotic resistant S. aureus since Nguyen teaches MRSA (hence, a methicillin resistant S. aureus) can be found in CTCL patients. Therefore claim 14 is included in this rejection. MRSA reads on claim 15.
As evidenced by the instant specification, CTCL is a mucosa associated cancer ([0018]). Therefore claims 16-18 are included in this rejection.
It would have been obvious to treat a CTCL patient by administering an endolysin specific for S. aureus. Nguyen teaches CTCL can be improved by treating S. aureus and Loessner teaches an endolysin can be used to treat the same bacteria. The skilled artisan would administer an endolysin with lytic activity against S. aureus to treat a condition caused by S. aureus. One would have had a reasonable expectation of success since Loessner teaches the compositions can be used to treat skin infections by S. aureus. One would have expected similar results since both references teach treating skin infections caused by Staphylococcus aureus. Because the administering an endolysin specific for S. aureus, it would be expected to take away the selective advantage of malignant T cells to proliferate as recited in preamble of the claim. Therefore claim 21 is rendered obvious.
Regarding independent claim 22: The teachings of Nguyen are reiterated. The art teaches patients with CTCL. The patients have malignant T cells. Nguyen teaches CTCL can be improved by treating S. aureus (an oncogenic bacterium). The art does not teach administration of an endolysin specific for S. aureus.
The teachings of Loessner are reiterated.
It would have been to administer an endolysin specific for S. aureus to a patient with CTCL. Nguyen teaches CTCL can be improved by treating S. aureus and Loessner teaches an endolysin can be used to treat the same bacteria. The skilled artisan would administer an endolysin with lytic activity against S. aureus to treat a condition caused by S. aureus. One would have had a reasonable expectation of success since Loessner teaches the compositions can be used to treat skin infections by S. aureus. One would have expected similar results since both references treat skin infections caused by S. aureus. Because administering an endolysin specific for S. aureus is rendered obvious, it would be expected to take away the selective advantage of CTCL T cells to proliferate as recited in step b) of the claim. Therefore claim 22 is rendered obvious.
Regarding independent claim 23: The teachings of Nguyen are reiterated. The art teaches patients with CTCL. The patients have malignant T cells. Nguyen teaches CTCL can be improved by treating S. aureus. The art does not teach administration of an endolysin specific for S. aureus.
The teachings of Loessner are reiterated.
It would have been to administer an endolysin specific for S. aureus to a patient with CTCL. Nguyen teaches CTCL can be improved by treating S. aureus and Loessner teaches an endolysin can be used to treat the same bacteria. The skilled artisan would administer an endolysin with lytic activity against S. aureus to treat a condition caused by S. aureus. One would have had a reasonable expectation of success since Loessner teaches the compositions can be used to treat skin infections by S. aureus. One would have expected similar results since both references treat skin infections caused by S. aureus. Because administering an endolysin specific for S. aureus is rendered obvious, it would be expected to restore the cytotoxic activity of CTCL T-cell-specific CD8 cytotoxic T-cells as recited in step b) of the claim. Therefore claim 23 is rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 04 May 2026 are acknowledged.
Argument 1: The Applicant argues it is has been demonstrated for the first time that the S. aureus alpha-toxin inhibits proliferation of non-malignant T- cells, but not malignant T-cells.
Response to Argument 1: Claim 1 is directed to a method of treating cancer. The arguments are directed to a scientific explanation of the differential effect of S. aureus alpha-toxin on malignant and non-malignant T cells. While claim 1 requires administering an endolysin specific for S. aureus, the subject is not required to have an S. aureus infection or a cancer with malignant T cells. Therefore the argument is not persuasive. Even arguendo the claim did require a subject with S. aureus infection, S. aureus inherently secretes alpha toxin (see evidentiary reference). Therefore it would be expected to have the claimed characteristics in a subject with malignant and non-malignant T cells.
Argument 2: The arguments state it was demonstrated for the first time that S. aureus alpha-toxin inhibits cytotoxic activity of CTCL-specific cytotoxic CD8 T cells.
Response to Argument 2: Claim 1 is not directed to CTCL. Regarding claims 22-23: The arguments are directed to a scientific explanation of the effect of S. aureus alpha-toxin on malignant and non-malignant T cells. The claims are directed to a method of treating cancer. Nguyen teaches a patient with CTCL. The art teaches S. aureus. As disclosed in the evidentiary reference, S. aureus inherently produces and secretes alpha toxin. Therefore said alpha toxin would be expected to have the characteristics argued by the Applicant.
Argument 3: The Applicant argues the prior art does not teach S. aureus alpha toxin inhibits proliferation of non-malignant T cells, but not malignant T cells. The Applicant argues the prior art does not provide evidence that administration of an endolysin specific for S. aureus effectively treats cancer.
Response to Argument 3: The Applicant’s argument is directed to a scientific explanation effect of S. aureus alpha-toxin on malignant and non-malignant T cells. Claim 1 recites a method of treating cancer. Nguyen is directed to CTCL with S. aureus infection (an oncogenic bacteria). The art teaches the disease can be improved by treating S. aureus. As evidenced by Berube et al., S. aureus inherently produces and secretes alpha toxin.
The Loessner reference teaches an endolysin specific for S. aureus (an oncogenic bacteria). The art teaches skin infections caused by S. aureus can be treated with said endolysin. It would have been to administer an endolysin specific for S. aureus to a patient with CTCL. Nguyen teaches CTCL can be improved by treating S. and Loessner teaches an endolysin can be used to treat the same bacteria. The skilled artisan would administer an endolysin with lytic activity against S. aureus to treat a condition caused by S. aureus. One would have had a reasonable expectation of success since Loessner teaches the compositions can be used to treat skin infections by S. aureus. One would have expected similar results since both references treat skin infections caused by S. aureus. Because administering an endolysin specific for S. aureus is rendered obvious, it would be expected to treat cancer are claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
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