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 .
Election/Restrictions
Applicant's election with traverse of Group I and clindamycin in the reply filed on 3/19/2026 is acknowledged. The traversal is on the ground(s) that multiple groups can be searched and examined together without undue burden and that considerable time and expense will be saved if all claims are considered at this time. This is not found persuasive for the following reasons:
Time and expense are not considerations in the propriety of a restriction requirement. Nor is the examiner convinced that examining multiple inventions will save the government any time or expense. Burden was previously addressed in the restriction requirement and applicant has not presented any reason to alter this determination.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-8, 10-20, and 28 are pending. Claims 10-11, 14-15, 18-19, and 28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Claims 1-8, 12-13, 16-17, and 20 are currently under examination.
Information Disclosure Statement
The information disclosure statement filed on 7/3/2023 has been considered. A signed copy is enclosed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2, 8, 12-13, 16-17, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 10,203,329. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The instant claims are drawn to methods of treating cancer comprising administering a therapeutically effective amount of one or more agents which are bactericidal, bacteriostatic and/or inhibit growth or activity of bacteria in a bacterial biofilm in the subject's gastrointestinal tract, wherein the bacterial biofilm comprises at least one bacterial type from Bacteroides and at least one bacterial type from Enterobacteriaceae; thereby treating the subject.
The claims of US Patent 10,203,329 are drawn to methods of treating colorectal cancer in a subject comprising detecting a bacterial biofilm that comprises Bacteroides and administering an antimicrobial or probiotic agent to a subject that reduces the size or density of the biofilm, thereby treating the cancer. The agent can be clindamycin. Therefore, the patented claims anticipate the instant claims.
Claims 1-2, 8, 12-13, 16-17, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11346840. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The instant claims are drawn to methods of treating cancer comprising administering a therapeutically effective amount of one or more agents which are bactericidal, bacteriostatic and/or inhibit growth or activity of bacteria in a bacterial biofilm in the subject's gastrointestinal tract, wherein the bacterial biofilm comprises at least one bacterial type from Bacteroides and at least one bacterial type from Enterobacteriaceae; thereby treating the subject.
The patented claims are drawn to methods of treating colorectal cancer in a subject comprising detecting a bacterial biofilm that comprises Bacteroides and administering an antimicrobial or probiotic agent to a subject that reduces the size or density of the biofilm, thereby treating the cancer. The agent can be clindamycin. Therefore, the patented claims anticipate the instant claims.
Claims 1-8, 12-13, 16-17, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11730774. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The instant claims are drawn to methods of treating cancer comprising administering a therapeutically effective amount of one or more agents which are bactericidal, bacteriostatic and/or inhibit growth or activity of bacteria in a bacterial biofilm in the subject's gastrointestinal tract, wherein the bacterial biofilm comprises at least one bacterial type from Bacteroides and at least one bacterial type from Enterobacteriaceae; thereby treating the subject.
The claims of US Patent 11730774 are drawn to methods of treating colorectal cancer in a subject comprising detecting a bacterial biofilm that comprises Bacteroides and administering an antimicrobial or probiotic agent to a subject that reduces the size or density of the biofilm, thereby treating the cancer. The agent can be clindamycin. Therefore, the patented claims anticipate the instant claims.
Improper Markush Group
Claims 2 and 12-13 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The claims encompass an extremely broad group of agents which are bactericidal, bacteriostatic and/or inhibit growth or activity of bacteria in a bacterial biofilm in the subject's gastrointestinal tract. These agents are vastly different in their chemical structures and effects. The species clearly do not share any structural features. While they do have a common use, that use does not flow from any shared structural feature. In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. §134 and 37 CFR 41.31(a)(1) (emphasis provided).
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-8, 12-13, 16-17, and 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 treatment of colorectal cancer in a subject with said cancer by administering an antibiotic that inhibits bacterial biofilms in the subject’s gastrointestinal tract, does not reasonably provide enablement for the full breadth of the claims as drawn. 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). But although the analysis and conclusion of a lack of enablement are based on these factors and the evidence as a whole, it is not necessary to discuss each factor in the enablement rejection. See MPEP § 2164.04.
The nature of the invention is a method of treating cancer or a neoplastic condition in a subject by administering a therapeutically effective amount of one or more agents which are bactericidal, bacteriostatic and/or inhibit growth or activity of bacteria in a bacterial biofilm in the subject's gastrointestinal tract, wherein the bacterial biofilm comprises at least one bacterial type from Bacteroides and at least one bacterial type from Enterobacteriaceae; thereby treating the subject.
The invention is exceedingly broad. The specification defines “treatment” to include prophylaxis. Therefore, not only must the administration be capable of curing, healing, alleviating, relieving, altering, remedying, ameliorating, improving or affecting the disease or disorder, or symptoms of the disease or disorder, but it must also be capable of preventing the cancer in the first place.
Not only are colorectal cancers encompassed, but the claims also encompass a disease, condition, trait, genotype or phenotype characterized by unregulated cell growth or replication as is known in the art; including, for example, leukemias, e.g., acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia, AIDS related cancers such as Kaposi's sarcoma; breast cancers; bone cancers such as Osteosarcoma, Chondrosarcomas, Ewing's sarcoma, Fibrosarcomas, Giant cell tumors, Adamantinomas, and Chordomas; Brain cancers such as Meningiomas, Glioblastomas, Lower-Grade Astrocytomas, Oligodendrocytomas, Pituitary Tumors, Schwannomas, and Metastatic brain cancers; cancers of the head and neck including various lymphomas such as mantle cell lymphoma, non-Hodgkins lymphoma, adenoma, squamous cell carcinoma, laryngeal carcinoma, gallbladder and bile duct cancers, cancers of the retina such as retinoblastoma, cancers of the esophagus, gastric cancers, multiple myeloma, ovarian cancer, uterine cancer, thyroid cancer, testicular cancer, endometrial cancer, melanoma, lung cancer, bladder cancer, prostate cancer, lung cancer (including non-small cell lung carcinoma), pancreatic cancer, sarcomas, Wilms' tumor, cervical cancer, head and neck cancer, skin cancers, nasopharyngeal carcinoma, liposarcoma, epithelial carcinoma, renal cell carcinoma, gallbladder adeno carcinoma, parotid adenocarcinoma, endometrial sarcoma, multidrug resistant cancers; and proliferative diseases and conditions, such as neovascularization associated with tumor angiogenesis, macular degeneration (e.g., wet/dry AMD), corneal neovascularization, diabetic retinopathy, neovascular glaucoma, myopic degeneration and other proliferative diseases and conditions such as restenosis and polycystic kidney disease, and other cancer or proliferative disease, condition, trait, genotype or phenotype that can respond to the modulation of its environment (e.g., treating the environment with an antibiotic effective against a bacterial bioform), alone or in combination with other therapies. It is noted that the term “cancer” thus includes conditions that are unrelated to what is generally known in the art as cancer, such as macular degeneration (e.g., wet/dry AMD), corneal neovascularization, diabetic retinopathy, neovascular glaucoma, myopic degeneration and other proliferative diseases and conditions such as restenosis and polycystic kidney disease. Cancer is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands.
Furthermore, the genus of agents that supposedly treat and prevent all of these cancers is enormous. Every agent that is bacteriostatic, bactericidal, or can inhibit growth or activity of bacteria in a biofilm in the subject’s gastrointestinal tract. Claim 2 specifically recites organic and inorganic molecules as well as natural or synthetic compounds. This literally encompasses every molecule on earth. Even amongst more specific groups, the number of agents is vast and includes hugely different compounds, as well as very large groups of different bacteria. Therefore, the claims encompass administering any antibacterial molecule in such a way that any cancer in any animal is treated or prevented, so long as the animal has a bacterial biofilm that comprises a strain of Bacteroides and Enterobacteriacae.
Malignant tumors are known in the art to be complex communities of oncogenically transforming cells that are associated with non-neoplastic cells and sometimes microbes like bacteria. It is known in the art that biofilms, particularly with Bacteroides and Enterobacteriacae, are associated with colorectal cancer. Therefore, it is plausible that reducing these using agents that are known to reduce the biofilms could be used to treat colorectal cancer. There is no art suggesting that any other form of cancer or that diseases such as diabetic retinopathy are related to biofilms in the gastrointestinal tract or that one could treat or prevent these conditions using an antibacterial agent or probiotic or any of the agents recited in claim 2.
Applicant’s examples are directed to showing a relationship between colorectal cancer and biofilms. There are no examples whatsoever that show treatment or prevention of any disease.
In the context of the provided definition, the Office finds that Applicant does not have evidence demonstrating that an antimicrobial agent or a probiotic agent can completely protect a person from neoplasia to develop or recur. Undue testing would have to be performed to establish that an antimicrobial agent or a probiotic agent can successfully inhibit a neoplastic condition since the effects of either agent are unpredictable and require thorough investigation.
Furthermore, the method is directed to treating “a neoplastic condition’, which is defined as “a disease state of human or an animal in which there are cells and/or tissues which proliferate abnormally” like cancers, sarcomas, tumors, leukemias, and lymphomas (page 6, Specification). These various types of neoplastic conditions are associated with different types of genetic changes and are known to affect different kinds of tissue. It should be noted that Applicant only characterized colorectal tumors and their association with microbial biofilms. No assay was conducted on other types of tissue. Thus, one with ordinary skill in the art would not have been able to predict if the experimental results can be extended to treatment of other neoplastic conditions.
According to MPEP § 2164.02, “For a claimed genus, representative examples together with a statement applicable to the genus as a whole will ordinarily be sufficient if one skilled in the art (in view of level of skill, state of the art and the information in the specification) would expect the claimed genus could be used in that manner without undue experimentation”. Due to the unpredictability of the invention and insufficient amount of working examples, claiming the treatment of all kinds of neoplastic condition is not enabling because, following the guidance presented therein, one cannot practice the claimed method without performing substantial experimentation to prove that other types of neoplastic condition on other tissues would necessarily be associated with bacterial biofilm.
The claims are therefore not enabled for the full breadth of the claims.
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 and 12-13 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 pre-AIA the applicant regards as the invention.
Claim 2 is indefinite because the Markush group contains antibiotics, antibacterial agents, antibodies, and cytokines each twice. Further, it is not clear what is encompassed by “cellular factor”. In addition, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Also, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitations antibacterial agents, small molecule inhibitors, organic or inorganic molecules, and natural or synthetic compounds, and the claim also recites antibiotics and small molecule inhibitors of toxins which are narrower statements of the range/limitation. With regard to organic or inorganic molecules and natural or synthetic compounds, everything on the list is a narrower statement of the limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Finally, claim 2 is dependent on itself.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. The claim requires the ETBF to encode or express a Bacteroides fragilis toxin (bft). However, all ETBF express this toxin. Therefore, the claim does not further limit the parent claim. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-2, 12-13, 16-17, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sears et al (WO2015/038731; IDS filed 7/3/2023).
The instant claims are drawn to methods of treating cancer comprising administering a therapeutically effective amount of one or more agents which are bactericidal, bacteriostatic and/or inhibit growth or activity of bacteria in a bacterial biofilm in the subject's gastrointestinal tract, wherein the bacterial biofilm comprises at least one bacterial type from Bacteroides and at least one bacterial type from Enterobacteriaceae; thereby treating the subject.
Sears et al disclose treatment of colon cancer by administration of antibiotics or probiotics that eliminate biofilms from the colon mucosa (see page 2, lines 18-21). The biofilm can comprise Bacteroides and Enterobacteriaceae, in a polymicrobial biofilm (see page 3, lines 3-5 and page 20, lines 27-32). The antibiotics to be administered include clindamycin (see page 3, lines 23-25).
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.
Claims 1-8, 12-13, 16-17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Sears et al (WO2015/038731; IDS filed 7/3/2023) in view of Viljoen et al (PLOS One, 10(3) e0119462, 2015, pages 1-21; IDS filed 7/3/2023).
The instant claims are drawn to methods of treating cancer comprising administering a therapeutically effective amount of one or more agents which are bactericidal, bacteriostatic and/or inhibit growth or activity of bacteria in a bacterial biofilm in the subject's gastrointestinal tract, wherein the bacterial biofilm comprises at least one bacterial type from Bacteroides and at least one bacterial type from Enterobacteriaceae; thereby treating the subject.
Sears et al disclose treatment of colon cancer by administration of antibiotics or probiotics that eliminate biofilms from the colon mucosa (see page 2, lines 18-21). The biofilm can comprise Bacteroides and Enterobacteriaceae, in a polymicrobial biofilm (see page 3, lines 3-5 and page 20, lines 27-32). The antibiotics to be administered include clindamycin (see page 3, lines 23-25).
Sears et al differs from the instant invention in that while they disclose treatment of colon cancer by administration of probiotics and antibiotics in order to eliminate biofilms containing Bacteroides and Enterobacteriacae, they do not specifically disclose that the biofilm should contain ETBF or E coli comprising pks genes and encoding or expressing colibactin.
It is noted that the pks gene island contains the colibactin genotoxin.
Viljoen et al disclose an association between Fusobacterium, ETBF, and pks+ E coli and colorectal cancer.
It would have been obvious to one of ordinary skill in the art, at the time of invention, to use the method of Sears et al on patients whose biofilms comprise ETBF or E coli comprising pks genes (which includes colibactin) because Sears et al discloses their treatment for use on all patients with biofilms in their gastrointestinal tract. This necessarily includes any Bacteroides, ETBF, pks+ E. coli, either singly or co-colonized in biofilms. Further, it would have been obvious to do so in light of Viljoen because these particular bacteria have been shown to be associated with colorectal cancer. One would have had a reasonable expectation of success because reducing the bacterial biofilms (comprising many types of bacteria) was disclosed as being useful for treating colorectal cancer.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian J Gangle whose telephone number is (571)272-1181. The examiner can normally be reached M-F, 9-6:30.
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/BRIAN GANGLE/Primary Examiner, Art Unit 1645
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