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 .
The response filed 2-18-2026 has been entered into the record.
Status of Claims
Claims 17-33 and 36-39 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election without traverse of Group I, P. stercorea and androgen deprivation therapy in the reply filed on 2-18-2026 is acknowledged.
Claims 17-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2-18-2026.
Claims 20-33 and 35-39 are under examination.
Information Disclosure Statement
The information disclosure statement filed 2-16-2024 has been considered. An initialed copy is enclosed.
Specification
The disclosure is objected to because of the following informalities:
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. Appropriate correction is required.
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 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(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.
Claims 20-33 and 36-39 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: 1) scope or breadth of the claims; 2) nature of the invention; 3) relative level of skill possessed by one of ordinary skill in the art; 4) state of, or the amount of knowledge in, the prior art; 5) level or degree of predictability, or a lack thereof, in the art; 6) amount of guidance or direction provided by the inventor; 7) presence or absence of working examples; and 8) quantity of experimentation required to make and use the claimed invention based upon the content of the supporting disclosure. When the above factors are weighed, it is the Office’s position that one skilled in the art could not practice the invention without undue experimentation.
While all of the factors have been considered, only those deemed necessary to establish a prima facie case are set forth below.
Scope or breadth of the claims
The instant claims are broadly drawn to methods of preventing, treating and/or inhibiting the development of prostate cancer or castration-resistant prostate cancer comprising administering a probiotic or postbiotic mixture comprising at least one bacterial strain selected from the genus Prevotella sp. to the subject. Dependent claims further comprise administration of other bacteria, antibiotics and drugs for androgen deprivation therapy.
Knowledge of the prior art
The prior art does not acknowledge that administration of Prevotella sp. or Prevotella sterocorea probiotics, postbiotics alone or in combination with antibiotics and androgen deprivation therapy are useful in the preventing/inhibiting of the development of prostate cancer or preventing/inhibiting the development of castration-resistant prostate cancer in any animal model where prevention/inhibition of development of cancer can be readily ascertained.
Guidance provided by inventor/working examples
The teachings of the specification are drawn to studies of the effect of Prevotella sterocorea prebiotics and postbiotics on the growth of androgen-insensitive prostate cancer cells in an animal model (castrated mice having tumors formed from prostate cancer cells). The experiment in Figure 4H provides for the administration in an animal model of castration-resistant prostate cancer, where administration treats the cancer by inhibition of tumor growth. It is clear that the prebiotic does not prevent or inhibit cancer. No other Prevotella sp were tested.
Level or degree of predictability
The prevention/inhibition of the development of cancer (e.g. inhibiting its development) is a long-sought goal in medicine. Treatment of established cancer is currently the only available modality. At the present time there is no therapeutic means to prevent/inhibit the development of cancer using any medicament/probiotic or postbiotic. The specification does not teach prevention of inhibition of the development of prostate cancer, all therapeutic regimens are given post development of tumors in the castration-resistant prostate cancer animal models provided. The art does not teach that prostate cancer is caused by bacteria such that antibiotics are useful in the inhibition of the development thereof. The art teaches that in dysbiosis, a systemic inflammatory state may be induced, predisposing remote anatomical sites to disease, including cancer. Due to the complexity of the potential interconnectedness between prostate cancer and the microbiome it is vital to further explore and understand the relationships that are involved (Porter et al (Prostate Cancer and Prostatic Diseases, 10.1038:s41391, 2018) see abstract). Porter et al teach that “at this point the exact relationship between bacteria present in the prostate and various disease states is unknown” (column 1, last page of text, second paragraph). Additionally, prostatic inflammation is a suggested risk factor for prostate cancer development and infections by pathogenic microorganisms are a hypothesized source of this inflammation. Several bacterial species are known to infect the prostate and cause bacterial prostatitis. Studies to determine whether prostatitis is a risk factor for prostate cancer development have reached conflicting results (see page 2, column 1, third paragraph). As such, there is no unifying accepted mechanism of the development of prostate cancer, including bacterial infection of the prostate or prostate inflammation as the cause.
Prevotella species are present in diverse animal species, and the genus has greater than 50 members and is likely to continue to expand as more environments are explored (see Amat et al (Microorganisms 8:1584 pages 1-22, 2020; see page 5 of 22, Table 1). Each of the different species have different characteristics and sometimes dual roles. Lu et al (Frontiers in Oncology, 16:1855577, August 2026 (pages 1-18)) teaches that Prevotella has a functional duality in gastrointestinal tumorigenesis and specific strains have been associated with either pro-tumorigenic or anti-tumorigenic depending upon the context. Lu et al demonstrates how much remains to be understood about the genus and a comprehensive synthesis of its strain-specific and context-dependent roles remains lacking (see page 01, abstract). It is still very difficult to fully decipher the role of any microorganism in a complex community such as the gut microbiota (see Cani, Gut 67:1716-1725, 2018; page 1720, column 2)/ Additionally, Lu et al teach that different proof of concept studies can reach different conclusions, with Prevotella copri being a typical case (see paragraphs bridging pages 1720-1721). In one case, administration provides for exacerbation of disease. In other animal models’ expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis and may play a role in pathogenesis (see (Scher et al, eLife 2:e01202, 2013 pages 1-20; see abstract in particular). The art teaches that the indirect effects of the microbiome on tumorigenesis are not well understood and could include modulation of antitumor responses and effects on host metabolism (see page 641, Markowski et al, European Urology 75:637-646, 2019). The art shows that no particular in vivo effect can be generalized from one specific species to the genus and that tumorigenesis is not understood. There is no evidence that any species can be used either as a probiotic or postbiotic to prevent or inhibit prostate cancer or castration-resistant prostate cancer. Finally, there is no evidence that any other Prevotella species would be effective to treat castration-resistant prostate cancer as encompassed by the claims.
Quantity of experimentation
The quantity of experimentation is extensive and unpredictable as demonstrated by sometimes opposing results depending upon animal model used as proof-of-concept. No other Prevotella species have been tested and a single species, Prevotella stercorea would not be recognized as representative of the genus as the genus has remarkable diversity of function.
In reaching a conclusion of undue experimentation, the following factors have been considered: quantity of experimentation necessary, amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the stat of the prior art, relative skill of those in the art, the predictability or unpredictability of the art and the breadth of the claims (In re Wands (CAFC) 8 USPQ2d 1400). However, in applications directed to inventions in arts but where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most
chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because it is not obvious from the disclosure of one species of Prevotella (Prevotella stercorea) for the treatment of castration-resistant prostate cancer, what other species in the genus will work and whether or not any one in the genus can prevent or inhibit the development of prostate cancer or castration-resistant prostate cancer as claimed.
In light of all the foregoing factors, the evidence as a whole suggests that the specification, in light of the level of knowledge in the art, does not enable one of ordinary skill to make or use the invention over the full scope of the instant claims without undue experimentation. Consequently, the claims are prima facie non-enabled as claimed.
Claim 35 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claims are drawn to a method of inhibiting the development of prostate cancer is a subject comprising administering a therapeutically effective amount of a pharmaceutic composition comprising vancomycin, ampicillin, neomycin and/or metronidazole. This claim language indicates that prostate cancer is not present in the subject but inhibits its development.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: 1) scope or breadth of the claims; 2) nature of the invention; 3) relative level of skill possessed by one of ordinary skill in the art; 4) state of, or the amount of knowledge in, the prior art; 5) level or degree of predictability, or a lack thereof, in the art; 6) amount of guidance or direction provided by the inventor; 7) presence or absence of working examples; and 8) quantity of experimentation required to make and use the claimed invention based upon the content of the supporting disclosure. When the above factors are weighed, it is the Office’s position that one skilled in the art could not practice the invention without undue experimentation.
While all of the factors have been considered, only those deemed necessary to establish a prima facie case are set forth below.
Scope or breadth of the claims
The instant claims are broadly drawn to inhibiting the development of prostate cancer by administering therapeutically effective amount of a pharmaceutic composition comprising vancomycin, ampicillin, neomycin and/or metronidazole.
Knowledge of the prior art
The prior art does not acknowledge that antibiotics and antifungals are useful in the inhibiting of the development in subjects not having prostate cancer.
Guidance provided by inventor/working examples
The specification teaches in Figure 20, that an undefined combination of broad spectrum antibiotics treats castration resistant prostate cancer, it does not inhibit its development. The inhibitory effect of any one of the claimed antibiotics alone or in combination is not disclosed by the specification. The specification does not provide any data that indicates that any one of the antibiotics alone or in combination inhibits the development of prostate cancer.
Level or degree of predictability
The prevention of cancer (e.g. inhibiting its development) is a long-sought goal in medicine. At the present time there is no therapeutic means to prevent/inhibit the development of cancer. The specification does not teach inhibition of the development of cancer, all therapeutic regimens are given post development of tumors in the animal models provided. The art does not teach that prostate cancer is caused by bacteria such that antibiotics are useful in the inhibition of the development thereof. The art teaches that in dysbiosis, a systemic inflammatory state may be induced, predisposing remote anatomical sites to disease, including cancer. Due to the complexity of the potential interconnectedness between prostate cancer and the microbiome it is vital to further explore and understand the relationships that are involved (Porter et al (Prostate Cancer and Prostatic Diseases, 10.1038:s41391, 2018) see abstract). Porter et al teach that “at this point the exact relationship between bacteria present in the prostate and various disease states is unknown” (column 1, last page of text, second paragraph). Additionally, prostatic inflammation is a suggested risk factor for prostate cancer development and infections by pathogenic microorganisms are a hypothesized source of this inflammation. Several bacterial species are known to infect the prostate and cause bacterial prostatitis. Studies to determine whether prostatitis is a risk factor for prostate cancer development have reached conflicting results (see page 2, column 1, third paragraph). As such, there is no unifying accepted mechanism of the development of prostate cancer, including bacterial infection of the prostate or prostate inflammation as the cause.
Quantity of experimentation
The skilled artisan would have to determine an appropriate animal model to study the development of prostate cancer to test to see if any one of the claimed antibiotics alone or in combination provide for inhibition of development (e.g. inhibition of initiation of cancer). The optimal model for developing improved methods of preventing, detecting and treating human prostate cancer is not known. The optimal model for such studies is not clear and the correlation of results in animal models with human patients with be the test of utility of the animal models (see Ittmann et al, Cancer Res, 73(9):2718-2736, 2013) see page 19, last paragraph). The as-filed specification does not teach the use of animal models having spontaneous generation of prostate cancer and as such, no apparent studies have been performed. The specification lacks guidance on the inhibition of development of prostate cancer. The skilled artisan would be performing studies on unknown animal models having an unknown an unestablished correlation with initiation of prostate cancer (e.g. development of prostate cancer). Even if one was selected, the skilled artisan would have to test each of the antibiotics alone or in various combinations to see if development/initiation is inhibited. The courts have held that the disclosure is insufficient when testing is necessary to determine the actual use or possible lack of use (In re Kirk and Petrow 153 USPQ 48 (CCPA 1967).
In light of the foregoing factors, the evidence as a whole suggests that the specification, in light of the level of knowledge in the art, does not enable one of ordinary skill to make or use the invention over the full scope of the instant claims without undue experimentation. Consequently, the claims are prima facie non-enabled.
Claim 30, 36, 37 and 38 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
As to claims 30 and 38, the claims are indefinite in the use of the acronym LHRH as it is unclear what this represents. While acronyms are permitted in the claims, they first must be preceded by what material/structure that they represent.
As to claim 37, the claim is prima facie indefinite because it depends on canceled claim 34.
As to claim 36, the claim is indefinite because claim 20 already administers a probiotic mixture and as such it is unclear what probiotic mixture is being further administered.
Claim 21, 23, 28, 29, 31, 32 and 36 are rejected under 35 U.S.C. 112(d), 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. As to claim 21, the claim recites a combination that falls outside the scope of claim 20. As such, it does not properly further limit the independent claim. As to claim 23, this claim is a combination or alternatively recited strains that falls outside the scope of claim 20, as it would exclude the bacterial strain of claim 20. As to claim 28, this claim refers to claim 20 as a probiotic mixture. Claim 20 is not drawn to a probiotic mixture and as such, this claim does not properly limit the scope of claim 20. The claim should be drafted as “The method of claim 20, further comprising administering a drug for androgen deprivation therapy to the subject”. The same issue exists in claim 29, the claim as it refers to the postbiotic mixture according to claim 25 is improper, since claim 25 is not drawn to a postbiotic mixture. Claims 31 and 32 are rejected for the same reasons as claims 28 and 29 respectively. The 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 20 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Copeland (US 2016/0220646).
Copeland teaches the treatment of cancer and prostate cancer specifically using a composition comprising oxygen scavenging membrane fragments with anaerobic bacterium such as Prevotella melaninogenica alone or in combination with other anaerobic bacteria including Bificobacterium adolenscentis (see page 16, claims 1, 8, 11 and 13). As such, Copeland teaches the claimed invention.
Claims 20, 22, 24, 25, 26, and 36 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Bellone et al (WO2020/109620, June 4, 2020),
Bellone et al that teach to the use of the bacterial strain Prevotella melaninogenica in the treatment and prevention of cancer or diabetes (see abstract). This includes derivatives such as lysates, metabolites and bacterial liquid culture supernatant. (see pages 2-3). Bellone et al teach prostate cancer treatment (see page 4, lines 4). Bellone et al teach the administration of ampicillin, vancomycin, neomycin and metronidazole to NOD mice followed by administration of P. melaninogenica (see page 28, line 24-page 29, line 7).
Although the reference is silent about the prevention/inhibition of the development of prostate cancer or castration-resistant prostate cancer, it does not appear that the claim language or limitations result in a manipulative difference in the method steps when compared to the prior art disclosure. See Bristol-Myers Squibb Company v. Ben Venue Laboratories 58 USPQ2d 1508 (CAFC 2001). {i}t is a general rule that merely discovering and claiming a new benefit of an old process cannot render the process again patentable. In re Woodruff, 16 USPQ2d 1934, 1936 (Fed. Cir. 1990). The mechanism of action does not have a bearing on the patentability of the invention if the invention was already known or obvious. Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 201 USPQ 658 (CCPA 1979). Granting a patent on the discovery of an unknown but inherent function would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art. In re Baxter Travenol Labs, 21 USPQ2d 1281 (Fed. Cir. 1991). See M.P.E.P. 2145.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. 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.
/Patricia Duffy/Primary Examiner, Art Unit 1645
Prosecution Insights