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 without traverse of Group 1, Claims 1-14, further electing SEQ ID NO: 1 in table 3 and melanoma in the reply filed on 1/5/2026 is acknowledged.
On 2/2/2026 the examiner telephoned M. Moynihan to clarify the election because SEQ ID NO: 1 in table 3 is not disclosed as related to melanoma. Mr. Moynihan clarified that SEQ ID NO: 241 was intended.
Instant SEQ ID NO: 241 is disclosed in Table 3 as an identifying sequence for Paracoccus marcusii. This same sequence is also disclosed in SEQ ID NO: 325 of Tables 4, 4.1 and 6. Therefore, SEQ ID NO: 325 is rejoined to the election as it is the same sequence as SEQ ID NO: 241.
Following this, claims 2 and 12 and 15-19 are withdrawn from prosecution, and claims 3, 6, and 10-11 and 14 are examined insofar as they require at least analyzing the abundance of the elected bacteria Paracoccus marcusii and for the cancer is melanoma, consonant with the election. Prior to any allowance the claims will be required to be amended to reflect the election.
Improper Markush
Claims 3, 6, 10-11 and 13-14 are rejected on the 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). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of different bacteria is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the multitude of different bacteria do not share a common single structural similarity. They are not art recognized equivalents because the prior art does not recognize them as functioning in the instantly claimed methods.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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 1 and 3-11 and 13-14 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 1 and 3-9 require administering an immunotherapy “on the basis of the abundance of said at least one bacteria” but the metes and bounds of this phrase are unclear. The instruction to deliver immunotherapy “on the basis” of bacterial abundance is not a term of art and it is unclear from the claims what it means to deliver the therapy “on the basis” of the abundance. It is unclear how the abundance is related to the administering.
Claims 10-11 and 13-14 recite “an abundance of said bacteria above a predetermined level” but the claims no not define the predetermined level or how the predetermined level is derived or obtained or what is from. This renders the claims indefinite because the metes and bounds of the claim cannot be determined as what value or values indicate cancer is undefined.
Claims 3, 6, 7, 10-14 are rejected because they recite tables. References to Tables in claims are not allowed unless necessary. By referring to a Table, the claims are made incomplete. MPEP 2173.05(s) states “Where possible, claims are to be complete in themselves.” Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.”
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1 and 3-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claim(s) recite(s) “analyzing for the abundance of at least one bacteria” which is sufficiently broad so as to encompass reviewing previously obtained data reporting the abundance of bacteria. This is a mental process that could occur in the mind. Further the claims recite administering treatment “on the basis of the abundance of said at least one bacteria” which sets forth an instruction to think about or consider the abundance of the bacteria when administering treatment, which is also a mental process abstract idea.
This judicial exception is not integrated into a practical application because although he claims recite “administering to the subject a therapeutically effective amount of an immunotherapy” this treatment is required to be given no matter the outcome of the analyzing or the thought about the abundance. No matter the results of the analyzing and thinking the same treatment, an “effective amount of an immunotherapy” is given. Therefore, the administering does not apply the judicial exception. The “analyzing” step, even if it is considered as a physical process step, is a data gathering step that does not apply or use the judicial exception in any way, and is therefore also does not integrate the judicial exception.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because methods of treating cancer with immunotherapy were widely known and well-established, routine and conventional at the time of the invention. The examiner takes Official notice to this fact. The “analyzing” step, even if it is considered as a physical process step, is a data gathering step that does not apply or use the judicial exception in any way, and is therefore also does not integrate the judicial exception. The step is recited at such a high level of generality that it is considered pre-solution data gathering. Furthermore, obtaining the microbiome profile of tumors was routine before the invention: see US 2018/0223338 (head and neck cancer), US 2018/0258495 (colon cancer), and Poore et al., discussed herein. The broadly claimed extra-solution activity does not transform the judicial exceptions into significantly more.
Claims 10, 11, 13-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a natural correlation without significantly more.
The method claim(s) recite(s) “analyzing the abundance of a bacteria” which is sufficiently broad so as to encompass reviewing previously obtained data reporting the abundance of bacteria. This is a mental process that could occur in the mind. Further the claims recite “bacteria above a predetermined level” which sets forth a comparison which is also a mental process abstract idea. Further the claims recite that the abundance of bacteria is indicative of cancer which is a statement of a natural phenomenon.
This judicial exception is not integrated into a practical application because although the claims recite “treating the cancer with an anti-cancer agent” this recitation is sufficient broad that it is not enough to be considered a particular treatment. It is so broad that it amounts to a direction of “apply” the judicial exception in a generic way. See MPEP 2106.04(d)(2). The claims do not apply or use the judicial exception in any other way. The “analyzing” step, even if it is considered as a physical process step, is a data gathering step that does not apply or use the judicial exception in any way, and is therefore also does not integrate the judicial exception.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because although the claims recite “treating the cancer with an anti-cancer agent” this recitation is sufficient broad that it is not enough to be considered a particular treatment. It is so broad that it amounts to a direction of “apply” the judicial exception in a generic way. Furthermore, methods of treating cancer were widely known and well-established, routine and conventional at the time of the invention. The examiner takes Official notice to this fact. The “analyzing” step, even if it is considered as a physical process step, is a data gathering step that does not apply or use the judicial exception in any way, and is therefore also does not integrate the judicial exception. The step is recited at such a high level of generality that it is considered pre-solution data gathering. Furthermore, obtaining the microbiome profile of tumors was routine before the invention: see US 2018/0223338 (head and neck cancer), US 2018/0258495 (colon cancer), and Poore et al., discussed herein.
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.
Claim(s) 1, 4, 5, and 8 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Poore (WO 2020/093040; filed 4 November 2019), as evidenced by Hugo et al. (2016, Cell 165, 35–44).
Poore teaches a method that includes analyzing for the abundance of at least one bacteria in the tumor microbiome of the subject and administering to the subject a therapeutically effective amount of an immunotherapy treatment on the basis of said at least one bacterium, thereby treating the cancer in the subject. See claim 1, 10, 22, 25, 33, 37, 42, 57, 58, 70, 71.
In particular, the reference teaches a method of predicting which subject will or will not respond to immunotherapy, particularly a PD-1 blockade (e.g. nivolumab, pembrolizumab), and further treating the disease based on the microbial features (¶0018 and 19). The reference teaches carrying out the analysis solely using nucleic acids of non-human origin from human tissue biopsy (¶0007). The reference teaches wherein the non-human sequences are microbial (¶0028).
The reference teaches that whole transcriptomic data microbial reads prior to receiving anti-PD-1 immunotherapy (¶0040, ¶00111). The reference teaches that the intratumoral RNA was used to distinguish patients who had a complete response versus those who had progressive disease, as well as to distinguish patients with complete response from partial response. See also figures 4A-4D. The dataset from Hugo et al. is inherently from patients having metastatic melanoma.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 10-11, 13-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Poore.
Poore teaches a method to diagnose and treat cancer (see title). Poore teaches a method of diagnosing disease, wherein the disease is melanoma (¶14). Poore teaches ROC and PR curves for melanoma, see ¶58, 62, 63, as well as associated figures 22, 26, and 27.
Poore does not specifically teach analyzing the abundance of a bacteria of the genus Paracoccus in a melanoma sample.
However, the reference teaches Paracoccus as among the bacteria that are microbial features that were detected in tumor genome samples (¶125, p. 83).
It would have been obvious to have assayed melanoma samples for Paracoccus genus bacteria, following the teachings of Poore that the melanoma tumor microbiome can be used to detect the presence of melanoma, and the list given in the table of Poore including Paracoccus. Following the teachings of Poore it would have been obvious to have determined the abundance (even if it were zero) of each of the bacteria listed in the table in order to identify the members of the bacterial composition of tumors, including melanoma, as taught by Poore. Instant claim 10 requires analyzing the abundance of a bacteria “of at least one…genus”. Here, “Paracoccus” is treated as an elected genus since the elected SEQ ID NO is for Paracoccus marcusii. The claims do not require detecting the bacteria as present in the tumor, merely analyzing for it. The “wherein” clause in part (a) states an inherent relationship between abundance and cancer, but does not require any further active step that distinguishes from the analyzing suggested by the reference.
Further, the claim requires treating the cancer with an anti-cancer agent. It would have been obvious to have analyzed a melanoma tumor for the abundance of Paracoccus, following the teachings of Poore et al. and then to treat the tumor by any conventional means as a way to prevent progression of the disease. Regarding claims 13-14, it would have been obvious to have analyzed the abundance of bacteria in both metastatic and non-metastatic tumor patients because Poore teaches that the microbiome can be used to diagnose and treat melanoma, and it was widely known at the time of the invention that both types of melanoma existed. The examiner takes Official notice to this fact.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Poore, as evidenced by Hugo in view of Lheure et al. (Acta Derm Venereol 2019; 99: 107–108).
The teachings of Poore as they pertain to claim 1 are given previously in this Office action and are fully incorporated here.
Poore does not teach a method wherein the cancer is a non-metastasized tumor.
Gellrich et al. teach treating non-metastatic melanoma patients with anti-PD1 immunotherapy (abstract and throughout).
It would have been prima facie obvious to have modified the method taught by Poore in view of Hugo so as to have assayed and treated non-metastatic melanoma patients because Gellrich et al. teach that anti-PD1 therapy was also successful at treating non-metastatic melanoma.
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, 3-11 and 13-15 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.
Instant claims 1 and those that depend from it are sufficiently broad so as to encompass treating any type of cancer on the basis of the abundance of as few as one bacteria, with melanoma and Paracoccus marcusii being elected for proescution. The claims are so broad that they encompass treating any cancer with any possible immunotherapy on the basis of the abundance of any bacteria in the tumor microbiome.
Regarding treating cancer “on the basis” of bacterial abundance, the disclosure teaches that to look at intra-tumor microbial signature that is correlated with response to immunotherapy, metastatic melanoma tumors that responded to immune checkpoint inhibitors (ICI) versus those that did not respond were compared (p. 82). Bacteria that were different between responders and non-responders were identified. The specification teaches that the 77 patients were stratified using the 46 different prevalent bacteria, and that patients with a prolonged progression free survival had a favorable tumor-microbiome signature.
The specification teaches that the differentially prevalent bacteria were identified that had a p<0.2, which suggests that at least some of the bacteria disclosed in Table 4 were not different at a statistically significant level. There is no written description of which bacteria were statistically different in one bacteria relative to another (See Thisted for a discussion of the meaning of a p-value).
Poore also teaches that a microbiome signature can be used to distinguish immunotherapy responders from non-responders for melanoma (see discussion previously in this Office action).
Determining microbial intratumoral signatures which can be used as a basis for treating cancer with immunotherapy is an unpredictable technology, as is evidenced at least by the instant specification which demonstrates that different cancers have different prevalences and abundance of bacteria. There is no way to predict, based on the disclosure which additional signatures other than the one disclosed could be used as a basis for treating melanoma or any other cancer.
Thus, while the specification demonstrates possession of a bacterial signature considering the intertumoral abundances of the bacteria listed in Table 4 could distinguish metastatic melanoma patients that are ICI responders from non-responders, and could thus be used as a basis for treating a patient with immunotherapy, the specification does not demonstrate possession commensurate in scope with the claims which encompass treating patients with immunotherapy of any type, for any type of cancer, and on the basis of the abundance of only one bacterial species, here P. marcusii, consonant with the election.
Claims 10-11 and 13-14 state that “the abundance of said bacteria above a predetermined level is indicative of the cancer.”
With regard to the elected melanoma and SEQ ID NO: 241, the specification discloses this combination in Table 3. Table 3 summarizes the different bacteria species that are prevalent in specific tumor types (p. 74). The specification teaches that the elected SEQ ID NO: 241, representing P. marcusii is present in 20% of melanoma tumors tested. However, the specification is silent as to what abundance in an individual sample of the P. marcusii is the “predetermined level” that would indicate cancer. Furthermore, the specification provides no evidence that P. marcusii is not simply present in 20% of skin samples or any control tissue.
Furthermore, the claims as written encompass indicating any type of cancer on the basis of the abundance of P. marcusii (SEQ ID NO: 241) in a tumor. The specification demonstrates that bacterial prevalences and abundances differ according to cancer type, and even subtype. There is no description in the specification as to how to use the family, order, genus or species abundance of the elected P. marcusii for the indication of the presence of melanoma or any other cancer, because there is no written description that the family, order, genus or species is present in melanoma at any abundance the distinguishes it from normal tissue or from tumors of other malignant or benign types.
Therefore, having considered all of this, it is concluded that applicant was no in possession of the invention at the time of filing.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US20180223338 teach analysis of the microbiome of tumors from head and neck cancer and teach methods for diagnosis.
US20180258495 teaches analysis of the tumor microbiome for colon cancer.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliet Switzer whose telephone number is (571)272-0753. The examiner can normally be reached Monday to Thursday, 8:00 AM-3:30 PM.
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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