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 .
Claims 1-20 are pending in this application and are being examined.
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.
Claim 13 is 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.
In claim 13, the claimed range “1010 or lower” is indefinite because the lower limit is not exactly defined and reads on zero. Therefore, the metes and bounds of the claim is not clearly set forth.
Suggestion to obviate the rejection: define the lower limit.
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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 14 is rejected under 35 U.S.C. 112(d) or pre-AIA 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.
In claim 14, lines 1-2, the phrase “wherein the freeze-dried microbial preparation comprises” fails to further limit the subject matter of claim 1 upon which it depends.
Suggestion to obviate the rejection: in claim 14, line 1, after preparation insert –further--.
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 § 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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Youngster et al. (JAMA, 2014, Vol. 312, No. 17, p. 1772-1778, published online on October 11, 2014, which is cited in IDS filed on 11/26/2024) and further in view of Lin et al. (which is cited in IDS filed on 11/26/2024).
Regarding claim 1, Youngster et al. teach method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, said method comprising orally administering to said subject a single dose of a pharmaceutical composition comprising a frozen fecal microbe preparation, wherein said single dose is capable of achieving a CDI clearance rate of at least 80% (oral administration of 15 capsules on two consecutive days of frozen fecal microbiota transplantation of FMT capsules from prescreened donors to unrelated patients with recurrent C. difficile infection and rate of clinical resolution of diarrhea of 90%) (see for example, p. 1772 “Objective”, “Design, …”, “Interventions”, “Results” and p. 1774 left-hand column 2nd and 3rd paragraphs and right-hand column last paragraph, and p. 1776 left-hand column “Discussion” – Continued on right-hand column).
Regarding claim 2, Youngster et al. teach said CDI clearance rate is calculated based on a patient population size of 20, 30, 40, 50, or 100 (twenty or 20 patients) (see for example, p. 1772 “Design, setting, and participants” and p. 1775 Table 1. Column corresponding to Patient Numbers) .
Regarding claim 7, Youngster et al. teach wherein said single dose achieves a CDI clearance rate of at least 90% (overall rate of diarrhea resolution of 90%) (See for example, p. 1774 right-hand column “Primary Outcome”/paragraph and p. 1776 left-hand column “Discussion”/paragraph).
Regarding claim 8, Youngster et al. teach wherein said subject is allowed only water for two hours prior to said administering said pharmaceutical composition, is allowed only water for two hours after said administering said pharmaceutical composition, or both (fast for 4 hours prior to capsule intake) (see for example, p. 1774 left-hand column 2nd paragraph “Study Procedure” lines 1-3).
Regarding claim 9, Youngster et al. teach wherein said subject experience little or no bowel movement irregularity, bloating, or flatulence within the first two weeks from administering said single dose (number of bowel movements over time in the study population) (see for example, p. 1776 left-hand column 3rd paragraph, also Figure 1 and its description).
Regarding claim 11, Youngster et al. do not teach any colon purgative prior to administering said single dose (see “Study Procedure”) (p. 1774 left-hand column 2nd paragraph).
Regarding claim 12, Youngster et al. teach the pharmaceutical composition is formulated as an enteric coated capsule or microcapsule, an acid-resistant capsule or microcapsule, an enteric coated tablet, an acid-resistant tablet, an enteric coated geltab, an acid-resistant geltab, an enteric coated pill, or an acid-resistant pill (commercially available acid resistance capsules DRCaps) (see p. 1774 left-hand column 1st paragraph).
Regarding claim 15, Youngster et al. teach wherein said CDI is primary CDI or recurrent CDI (recurrent CDI) (see p. 1773 left- hand column “Methods”/paragraph lines 3-5).
Regarding claim 16, Youngster et al. teach wherein said fecal microbe preparation comprises a donor's entire or substantially complete microbiota (concentrated single donor feces) (p. 1774 left-hand column 1st paragraph).
Regarding claim 17, Youngster et al. teach wherein the preparation of said fecal microbe preparation involves a separation step selected from the group consisting of filtering, sieving, differential centrifugation, density gradient centrifugation, filtration, chromatography, and a combination thereof (concentrating fecal suspension by centrifugation) (p. 1773 right-hand column last paragraph).
Regarding claim 18, Youngster et al. teach wherein said fecal microbe preparation comprises a preparation of viable flora in proportional content that resembles a normal healthy human fecal flora (fecal microbe preparation comprises feces/fecal microbiota of healthy donors) (p. 1774 left-hand column 1st paragraph, and p. 1772 “Interventions”).
Regarding claim 19, Youngster et al. teach wherein said subject is pretreated with an antibiotic prior to administration of said composition (CDI patients having relapsed after vancomycin treatment) (p. 1773 right-hand column 1st paragraph).
Regarding claim 20, Youngster et al. teach wherein said antibiotic is selected from the group consisting of amoxicillin, tetracycline, metronidazole, rifabutin, clarithromycin, clofazimine, vancomycin, rifampicin, nitroimidazole, chloramphenicol, and a combination thereof (CDI patients having relapse after vancomycin treatment) (p. 1773 right-hand column 1st paragraph).
Regarding the limitations of claims 3-6, although Youngster et al. do not explicitly teach the claimed relative abundance of Proteobacteria in said subject's stool decreases by at least 50% within 3 to 6 days from administering … (claim 3), the relative abundance of one or more bacteria selected from the group consisting of Firmicutes and Bacteroidetes in said subject's stool increases by at least 50% within 3 to 6 days from administering … (claim 4), the alpha diversity within Firmicutes in said subject's stool increases by at least 100% within 3 to 6 days from administering … (claim 5), and the alpha diversity within Bacteroidetes in said subject's stool remains substantially unchanged within 6 days, 21 days, or 60 days from administering … (claim 6), however because Youngster et al. teach the step of orally administering to a subject having CDI a pharmaceutical composition comprising frozen fecal microbe preparation and achieving a CDI clearance rate of at least 80%, therefore the claimed properties (%) of relative abundance of Proteobacteria in said subject's stool decreases by at least 50% …, the relative abundance of one or more bacteria selected from the group consisting of Firmicutes and Bacteroidetes in said subject's stool increases by at least 50% …, the alpha diversity within Firmicutes in said subject's stool increases by at least 100% …, and the alpha diversity within Bacteroidetes in said subject's stool remains substantially unchanged within 6 days, 21 days, or 60 days from administering …, not explicitly taught are inherent to the method of Youngster et al. (Also see MPEP 2112 II.).
Youngster et al. do not teach a single dose and the preparation is freeze-dried (claim 1), pharmaceutical composition is capable of being stored at room temperature for at least 3 days prior to said administering (claim 10), the single dose comprises a total cell count of 1010 or greater (claim 13), and said freeze-dried fecal microbe preparation comprises a cryoprotectant selected from the group consisting of trehalose, glucose, fructose, sucrose, lactose, ribose, mannitol, erythritol, arabitol, sorbitol, alanine, glycine, proline, sand a combination thereof (claim 14).
However, as mentioned above Youngster et al. teach oral administration of a dose, i.e., 15 capsules on two consecutive days of frozen FMT capsules, and further the frozen fecal microbe preparation was concentrated and comprises a cryoprotectant (resuspended in one-tenth the volume of initial sample with glycerol) (p. 1773 right-hand column last paragraph).
Moreover, Lin et al. teach a single dose of freeze-dried (or lyophilized) fecal microbe preparation which comprises a cryoprotectant (trehalose and sucrose), Lin et al. teach FMT comprising a total cell count of 1010 or greater (viable count of 1.5 X 1011) experienced less viability loss after storage at ambient temperature for at least 3 days (over 12 weeks) and provide improved availability and viable fecal microbiota cells as lyophilize powder that can be incorporated into capsules for oral administration compared to the frozen preparation (see Abstract).
Therefore, a person of ordinary skill in the art before the effective filing date of the invention recognizing the advantages freeze drying the fecal microbe preparation including improved availability and further concentrating cells to a lyophilized powder, would have been motivated to modify the fecal microbiota preparation taught by Youngster et al. based on the teachings of Lin et al. by freeze drying the fecal microbe preparation of Youngster et al. prior to encapsulating with reasonable expectation of success in further concentrating the fecal microbiota preparation which comprises 1010 or greater total cell count and providing the claimed single dose pharmaceutical composition comprising a freeze-dried fecal microbe preparation and orally administering said single dose with reasonable expectation of success in providing the claimed method for treating a Clostridium difficile infection (CDI) in a subject in need thereof. The claimed method would have been obvious because Youngster et al. teach a method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, said method comprising orally administering to said subject a dose of a pharmaceutical composition comprising a frozen fecal microbe preparation, wherein said the dose is capable of achieving a CDI clearance rate of at least 80%, and because Lin et al. teach freeze-dried fecal microbe preparation comprises total cell count of 1010 or greater experienced less viability loss after storage at ambient temperature for at least 3 days and provides improved availability and viable cells that can be incorporated into capsules for oral administration compared to the frozen preparation.
Double Patenting Rejection:
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
A)
Claims 1-7, 9, 13, 14 and 18-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 4, 6, 7, 9, 10, 12, 13 16 and 17 of U.S. Patent No. 12,186,349 B2. Although the claims at issue are not identical, they are not patentably distinct from each other in view of the side by side comparison (see below table) of the limitations of claimed method of instant application and method of claims 1-3, 4, 6, 7, 9, 10, 12, 13 16 and 17 of U.S. Patent No. 12,186,349 B2.
Claims U.S. Patent No. 12,186,349 B2:
Claims of instant Application:
1. A method for treating or clearing a Clostridium difficile infection (CDI) in a subject in need thereof, the method comprising administering to the subject a single dose of a pharmaceutical composition comprising a freeze-dried fecal microbe preparation derived from a stool of a healthy human donor, wherein (a) a relative abundance of Proteobacteria in the subject's stool decreases by at least 40%, (b) a relative abundance of Firmicutes in the subject's stool increases by at least 50%, or (c) a relative abundance of Bacteroidetes in the subject's stool increases by at least 50%, within 3 to 6 days from administering the single dose relative to a baseline abundance immediately prior to administering the single dose, wherein the method achieves a CDI clearance rate as determined by the absence of detectable C. difficile toxin B DNA in the stool of the subject.
3. The method of claim 1, wherein the single dose achieves a CDI clearance rate of at least 60%.
1. A method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, said method comprising orally administering to said subject a single dose of a pharmaceutical composition comprising a freeze-dried fecal microbe preparation, wherein said single dose is capable of achieving a CDI clearance rate of at least 80%.
2. The method of claim 1, wherein the method achieves a CDI clearance rate as calculated based on a patient population size selected from the group consisting of 20, 30, 40, 50, and 100.
2. The method of claim 1, wherein said CDI clearance rate is calculated based on a patient population size of 20, 30, 40, 50, or 100.
1. , … wherein (a) a relative abundance of Proteobacteria in the subject's stool decreases by at least 40%, … within 3 to 6 days from administering the single dose relative to a baseline abundance immediately prior to administering the single dose, …
3. The method of claim 1, wherein the relative abundance of Proteobacteria in said subject's stool decreases by at least 50% within 3 to 6 days from administering said single dose relative to a baseline abundance immediately prior to administering said single dose.
1. wherein …, (b) a relative abundance of Firmicutes in the subject's stool increases by at least 50%, or (c) a relative abundance of Bacteroidetes in the subject's stool increases by at least 50%, within 3 to 6 days from administering the single dose relative to a baseline abundance immediately prior to administering the single dose, …
4. The method of claim 1, wherein the relative abundance of one or more bacteria selected from the group consisting of Firmicutes and Bacteroidetes in said subject's stool increases by at least 50% within 3 to 6 days from administering said single dose relative to a baseline abundance immediately prior to administering said single dose.
4. The method of claim 1, wherein the pharmaceutical composition is stable when placed at room temperature for at least three days prior to the administering.
10. The method of claim 1, wherein said pharmaceutical composition is capable of being stored at room temperature for at least 3 days prior to said administering.
6. The method of claim 1, wherein the alpha diversity within Firmicutes in the subject's stool increases by at least 100% within 3 to 6 days from administering the single dose relative to a baseline diversity immediately prior to administering the single dose.
5. The method of claim 1, wherein the alpha diversity within Firmicutes in said subject's stool increases by at least 100% within 3 to 6 days from administering said single dose relative to a baseline diversity immediately prior to administering said single dose.
7. The method of claim 1, wherein the alpha diversity within Bacteroidetes in the subject's stool remains substantially unchanged within 6 days, 21 days, or 60 days from administering the single dose relative to a baseline diversity immediately prior to administering the single dose.
6. The method of claim 1, wherein the alpha diversity within Bacteroidetes in said subject's stool remains substantially unchanged within 6 days, 21 days, or 60 days from administering said single dose relative to a baseline diversity immediately prior to administering said single dose.
3. The method of claim 1, wherein the single dose achieves a CDI clearance rate of at least 60%.
7. The method of claim 1, wherein said single dose achieves a CDI clearance rate of at least 90%.
9. The method of claim 1, wherein the pharmaceutical composition is formulated in a format selected from the group consisting of an enteric coated capsule, an enteric coated microcapsule, an acid-resistant capsule, an acid-resistant microcapsule, an enteric coated tablet, an acid-resistant tablet, an enteric coated gel tab, an acid-resistant gel tab, an enteric coated pill, and an acid-resistant pill.
9. The method of claim 1, wherein the pharmaceutical composition is formulated in a format selected from the group consisting of an enteric coated capsule, an enteric coated microcapsule, an acid-resistant capsule, an acid-resistant microcapsule, an enteric coated tablet, an acid-resistant tablet, an enteric coated gel tab, an acid-resistant gel tab, an enteric coated pill, and an acid-resistant pill.
10. The method of claim 1, wherein the freeze-dried fecal microbe preparation further comprises a cryoprotectant selected from the group consisting of trehalose, glucose, fructose, sucrose, lactose, ribose, mannitol, erythritol, arabitol, sorbitol, alanine, glycine, proline, and a combination thereof.
14. The method of claim 1, wherein said freeze-dried fecal microbe preparation comprises a cryoprotectant selected from the group consisting of trehalose, glucose, fructose, sucrose, lactose, ribose, mannitol, erythritol, arabitol, sorbitol, alanine, glycine, proline, sand a combination thereof.
12. The method of claim 1, wherein the subject is pretreated with an antibiotic prior to administration of the pharmaceutical composition.
19. The method of claim 1, wherein said subject is pretreated with an antibiotic prior to administration of said composition.
13. The method of claim 12, wherein the antibiotic is selected from the group consisting of amoxicillin, tetracycline, metronidazole, rifabutin, clarithromycin, clofazimine, vancomycin, rifampicin, nitroimidazole, chloramphenicol, and a combination thereof.
20. The method of claim 19, wherein said antibiotic is selected from the group consisting of amoxicillin, tetracycline, metronidazole, rifabutin, clarithromycin, clofazimine, vancomycin, rifampicin, nitroimidazole, chloramphenicol, and a combination thereof.
16. The method of claim 1, wherein the single dose comprises a total cell count or total live cell count of between 10.sup.3 and 10.sup.10.
13. The method of claim 1, wherein said single dose comprises a total cell count of 1010 or greater.
17. The method of claim 1, wherein the subject had no prior exposure to fecal microbiota-based therapy.
18. The method of claim 1, wherein said fecal microbe preparation comprises a preparation of viable flora in proportional content that resembles a normal healthy human fecal flora.
Therefore, in view of the method for clearing a Clostridium difficile infection (CDI) in a subject in need, as disclosed/taught by claims 1-3, 4, 6, 7, 9, 10, 12, 13 16 and 17 of U.S. Patent No. 12,186,349 B2 (See above table for claim by claim comparison), it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to apply the method for clearing a Clostridium difficile infection (CDI) in a subject in need to provide the method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, as claimed by claims 1-7, 9, 13, 14 and 18-20 of instant application.
B)
Claims 1-4, 7, 8, 10, 12-16 and 18-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 4-12, 15-17, and 19-24 of U.S. Patent No. 11,819,523 B2. Although the claims at issue are not identical, they are not patentably distinct from each other in view of the side by side comparison (see below table) of the limitations of claimed method of instant application and method(s) of claims 1, 12, 4-12, 15-17, and 19-24 of U.S. Patent No. 11,819,523 B2.
Claims of U.S. Patent No. 11,819,523 B2:
Claims of instant Application:
1. A method for clearing a Clostridium difficile infection (CDI) in a subject in need thereof, the method comprising pretreating the subject with an antibiotic regimen, the method further comprising administering to the subject a single dose of a pharmaceutical composition comprising a double-encapsulated microbial preparation derived from a stool of a healthy human donor, wherein the microbial preparation is free of an antibiotic resistant population of bacteria, wherein the pharmaceutical composition achieves at least a 70% CDI clearance rate following administration to the subject as determined by the absence of detectable C. difficile toxin B DNA in the stool of the subject.
17. A method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, the method comprising administering to the subject a single treatment regimen comprising the oral administration of single dose of a pharmaceutical composition comprising a microbial preparation derived from a stool of a healthy human donor, wherein the microbial preparation is free of an antibiotic resistant population of bacteria, wherein the pharmaceutical composition is stable when placed at room temperature for at least three (3) days, and wherein the single dose is administered within one day and the single dose achieves at least a 70% CDI clearance rate following administration to the subject as determined by the absence of detectable C. difficile toxin B DNA in the stool of the subject.
4. The method of claim 1, wherein the pharmaceutical composition comprises a freeze-dried microbial preparation.
15. The method of claim 1, wherein the pharmaceutical composition achieves at least a 75% CDI clearance rate following administration to the subject.
16. The method of claim 15, wherein the pharmaceutical composition achieves at least an 80% CDI clearance rate following administration to the subject.
1. A method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, said method comprising orally administering to said subject a single dose of a pharmaceutical composition comprising a freeze-dried fecal microbe preparation, wherein said single dose is capable of achieving a CDI clearance rate of at least 80%.
5. The method of claim 1, wherein the CDI clearance rate is calculated based on a patient population size selected from the group consisting of 20, 30, 40, 50, and 100.
2. The method of claim 1, wherein said CDI clearance rate is calculated based on a patient population size of 20, 30, 40, 50, or 100.
8. The method of claim 1, wherein a relative abundance of Proteobacteria in the subject's stool decreases by at least 50% within 3 to 6 days from administering the single dose relative to a baseline abundance immediately prior to administering the single dose.
20. The method of claim 17, wherein a relative abundance of Proteobacteria in the subject's stool decreases by at least 50% within 3 to 6 days from administering the single dose relative to a baseline abundance immediately prior to administering the single dose.
3. The method of claim 1, wherein the relative abundance of Proteobacteria in said subject's stool decreases by at least 50% within 3 to 6 days from administering said single dose relative to a baseline abundance immediately prior to administering said single dose.
9. The method of claim 1, wherein a relative abundance of Firmicutes in the subject's stool increases by at least 50% within 3 to 6 days from administering the single dose relative to a baseline abundance immediately prior to administering the single dose.
10. The method of claim 1, wherein a relative abundance of Bacteroidetes in the subject's stool increases by at least 50% within 3 to 6 days from administering the single dose relative to a baseline abundance immediately prior to administering the single dose.
21. The method of claim 17, wherein a relative abundance of one or more bacteria selected from the group consisting of Firmicutes and Bacteroidetes in the subject's stool increases by at least 50% within 3 to 6 days from administering the single dose relative to a baseline abundance immediately prior to administering the single dose.
4. The method of claim 1, wherein the relative abundance of one or more bacteria selected from the group consisting of Firmicutes and Bacteroidetes in said subject's stool increases by at least 50% within 3 to 6 days from administering said single dose relative to a baseline abundance immediately prior to administering said single dose.
6. The method of claim 1, wherein the single dose achieves a CDI clearance rate of at least 90%.
7. The method of claim 1, wherein said single dose achieves a CDI clearance rate of at least 90%.
2. The method of claim 1, wherein the pharmaceutical composition is stable when placed at room temperature for at least three (3) days.
10. The method of claim 1, wherein said pharmaceutical composition is capable of being stored at room temperature for at least 3 days prior to said administering.
22. The method of claim 17, wherein the pharmaceutical composition is formulated in a format selected from the group consisting of an enteric coated capsule, an enteric coated microcapsule, an acid-resistant capsule, an acid-resistant microcapsule, an enteric coated tablet, an acid-resistant tablet, an enteric coated gel tab, an acid-resistant gel tab, an enteric coated pill, and an acid-resistant pill.
12. The method of claim 1, wherein said pharmaceutical composition is formulated as an enteric coated capsule or microcapsule, an acid-resistant capsule or microcapsule, an enteric coated tablet, an acid-resistant tablet, an enteric coated geltab, an acid-resistant geltab, an enteric coated pill, or an acid-resistant pill.
7. The method of claim 1, wherein the single dose comprises a total cell count of 10.sup.10 or greater.
23. The method of claim 17, wherein the single dose comprises a total cell count of 10.sup.10 or greater.
13. The method of claim 1, wherein said single dose comprises a total cell count of 1010 or greater.
11. The method of claim 4, wherein the freeze-dried microbial preparation further comprises trehalose.
14. The method of claim 1, wherein said freeze-dried fecal microbe preparation comprises a cryoprotectant selected from the group consisting of trehalose, glucose, fructose, sucrose, lactose, ribose, mannitol, erythritol, arabitol, sorbitol, glycine, proline, sand a combination thereof.
12. The method of claim 1, wherein the CDI is primary CDI or recurrent CDI.
19. The method of claim 17, wherein the CDI is primary CDI or recurrent CDI.
15. The method of claim 1, wherein said CDI is primary CDI or recurrent CDI.
24. The method of claim 17, wherein the microbial preparation comprises a preparation selected from the group consisting of a donor's entire microbiota and a donor's substantially complete microbiota.
16. The method of claim 1, wherein said fecal microbe preparation comprises a donor's entire or substantially complete microbiota.
24. The method of claim 17, wherein the microbial preparation comprises a preparation selected from the group consisting of a donor's entire microbiota and a donor's substantially complete microbiota.
18. The method of claim 1, wherein said fecal microbe preparation comprises a preparation of viable flora in proportional content that resembles a normal healthy human fecal flora.
1. A method for clearing a Clostridium difficile infection (CDI) in a subject in need thereof, the method comprising pretreating the subject with an antibiotic regimen, …
19. The method of claim 1, wherein said subject is pretreated with an antibiotic prior to administration of said composition.
13. The method of claim 1, wherein the antibiotic is selected from the group consisting of amoxicillin, tetracycline, metronidazole, rifabutin, clarithromycin, clofazimine, vancomycin, rifampicin, nitroimidazole, chloramphenicol, and a combination thereof.
20. The method of claim 19, wherein said antibiotic is selected from the group consisting of amoxicillin, tetracycline, metronidazole, rifabutin, clarithromycin, clofazimine, vancomycin, rifampicin, nitroimidazole, chloramphenicol, and a combination thereof.
Therefore, in view of the method for clearing a Clostridium difficile infection (CDI) in a subject in need thereof and the method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, as disclosed/taught by claims 1, 12, 4-12, 15-17, and 19-24 of U.S. Patent No. 11,819,523 B2 (See above table for claim by claim comparison), it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to apply the method for clearing a Clostridium difficile infection (CDI) in a subject in need thereof and the method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, as disclosed/taught by claims 1, 12, 4-12, 15-17, and 19-24 of U.S. Patent No. 11,819,523 B2 to provide the claimed method for treating a Clostridium difficile infection (CDI) in a subject in need, of claims 1-4, 7, 8, 10, 12-16 and 18-20 of instant Application.
C)
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1-20 of U.S. Patent No. 10,849,936 B2. Because the method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, as disclosed by claims 1-20 of U.S. Patent No. 10,849,936 B2, anticipate the claimed method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, of claims 1-20 of instant Application.
Claims U.S. Patent No. 10,849,936 B2:
Claims of instant Application:
1. A method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, said method comprising orally administering to said subject a single dose of a pharmaceutical composition comprising a freeze-dried fecal microbe preparation, wherein said single dose is administered within one day and said single dose is capable of achieving a CDI clearance rate of at least 80%.
1. A method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, said method comprising orally administering to said subject a single dose of a pharmaceutical composition comprising a freeze-dried fecal microbe preparation, wherein said single dose is capable of achieving a CDI clearance rate of at least 80%.
2. The method of claim 1, wherein said CDI clearance rate is calculated based on a patient population size of 20, 30, 40, 50, or 100.
2. The method of claim 1, wherein said CDI clearance rate is calculated based on a patient population size of 20, 30, 40, 50, or 100.
3. The method of claim 1, wherein the relative abundance of Proteobacteria in said subject's stool decreases by at least 50% within 3 to 6 days from administering said single dose relative to a baseline abundance immediately prior to administering said single dose.
3. The method of claim 1, wherein the relative abundance of Proteobacteria in said subject's stool decreases by at least 50% within 3 to 6 days from administering said single dose relative to a baseline abundance immediately prior to administering said single dose.
4. The method of claim 1, wherein the relative abundance of one or more bacteria selected from the group consisting of Firmicutes and Bacteroidetes in said subject's stool increases by at least 50% within 3 to 6 days from administering said single dose relative to a baseline abundance immediately prior to administering said single dose.
4. The method of claim 1, wherein the relative abundance of one or more bacteria selected from the group consisting of Firmicutes and Bacteroidetes in said subject's stool increases by at least 50% within 3 to 6 days from administering said single dose relative to a baseline abundance immediately prior to administering said single dose.
5. The method of claim 1, wherein the alpha diversity within Firmicutes in said subject's stool increases by at least 100% within 3 to 6 days from administering said single dose relative to a baseline diversity immediately prior to administering said single dose.
5. The method of claim 1, wherein the alpha diversity within Firmicutes in said subject's stool increases by at least 100% within 3 to 6 days from administering said single dose relative to a baseline diversity immediately prior to administering said single dose.
6. The method of claim 1, wherein the alpha diversity within Bacteroidetes in said subject's stool remains substantially unchanged within 6 days, 21 days, or 60 days from administering said single dose relative to a baseline diversity immediately prior to administering said single dose.
6. The method of claim 1, wherein the alpha diversity within Bacteroidetes in said subject's stool remains substantially unchanged within 6 days, 21 days, or 60 days from administering said single dose relative to a baseline diversity immediately prior to administering said single dose.
7. The method of claim 1, wherein said single dose achieves a CDI clearance rate of at least 90%.
7. The method of claim 1, wherein said single dose achieves a CDI clearance rate of at least 90%.
8. The method of claim 1, wherein said subject is allowed only water for two hours prior to said administering said pharmaceutical composition, is allowed only water for two hours after said administering said pharmaceutical composition, or both.
8. The method of claim 1, wherein said subject is allowed only water for two hours prior to said administering said pharmaceutical composition, is allowed only water for two hours after said administering said pharmaceutical composition, or both.
9. The method of claim 1, wherein said subject experience little or no bowel movement irregularity, bloating, or flatulence within the first two weeks from administering said single dose.
9. The method of claim 1, wherein said subject experience little or no bowel movement irregularity, bloating, or flatulence within the first two weeks from administering said single dose.
10. The method of claim 1, wherein said pharmaceutical composition is capable of being stored at room temperature for at least 3 days prior to said administering.
10. The method of claim 1, wherein said pharmaceutical composition is capable of being stored at room temperature for at least 3 days prior to said administering.
11. The method of claim 1, wherein said method requires no colon purgative prior to administering said single dose.
11. The method of claim 1, wherein said method requires no colon purgative prior to administering said single dose.
12. The method of claim 1, wherein said pharmaceutical composition is formulated as an enteric coated capsule or microcapsule, an acid-resistant capsule or microcapsule, an enteric coated tablet, an acid-resistant tablet, an enteric coated geltab, an acid-resistant geltab, an enteric coated pill, or an acid-resistant pill.
12. The method of claim 1, wherein said pharmaceutical composition is formulated as an enteric coated capsule or microcapsule, an acid-resistant capsule or microcapsule, an enteric coated tablet, an acid-resistant tablet, an enteric coated geltab, an acid-resistant geltab, an enteric coated pill, or an acid-resistant pill.
13. The method of claim 1, wherein said single dose comprises a total cell count of 10.sup.10 or greater.
13. The method of claim 1, wherein said single dose comprises a total cell count of 1010 or greater.
14. The method of claim 1, wherein said freeze-dried fecal microbe preparation comprises a cryoprotectant selected from the group consisting of trehalose, glucose, fructose, sucrose, lactose, ribose, mannitol, erythritol, arabitol, sorbitol, alanine, glycine, proline, sand a combination thereof.
14. The method of claim 1, wherein said freeze-dried fecal microbe preparation comprises a cryoprotectant selected from the group consisting of trehalose, glucose, fructose, sucrose, lactose, ribose, mannitol, erythritol, arabitol, sorbitol, alanine, glycine, proline, sand a combination thereof.
15. The method of claim 1, wherein said CDI is primary CDI or recurrent CDI.
15. The method of claim 1, wherein said CDI is primary CDI or recurrent CDI.
16. The method of claim 1, wherein said fecal microbe preparation comprises a donor's entire or substantially complete microbiota.
16. The method of claim 1, wherein said fecal microbe preparation comprises a donor's entire or substantially complete microbiota.
17. The method of claim 1, wherein the preparation of said fecal microbe preparation involves a separation step selected from the group consisting of filtering, sieving, differential centrifugation, density gradient centrifugation, filtration, chromatography, and a combination thereof.
17. The method of claim 1, wherein the preparation of said fecal microbe preparation involves a separation step selected from the group consisting of filtering, sieving, differential centrifugation, density gradient centrifugation, filtration, chromatography, and a combination thereof.
18. The method of claim 1, wherein said fecal microbe preparation comprises a preparation of viable flora in proportional content that resembles a normal healthy human fecal flora.
18. The method of claim 1, wherein said fecal microbe preparation comprises a preparation of viable flora in proportional content that resembles a normal healthy human fecal flora.
19. The method of claim 1, wherein said subject is pretreated with an antibiotic prior to administration of said composition.
19. The method of claim 1, wherein said subject is pretreated with an antibiotic prior to administration of said composition.
20. The method of claim 19, wherein said antibiotic is selected from the group consisting of amoxicillin, tetracycline, metronidazole, rifabutin, clarithromycin, clofazimine, vancomycin, rifampicin, nitroimidazole, chloramphenicol, and a combination thereof.
20. The method of claim 19, wherein said antibiotic is selected from the group consisting of amoxicillin, tetracycline, metronidazole, rifabutin, clarithromycin, clofazimine, vancomycin, rifampicin, nitroimidazole, chloramphenicol, and a combination thereof.
Therefore, in view of the above, the method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, as disclosed by claims 1-20 of U.S. Patent No. 10,849,936 B2, anticipate the claimed method for treating a Clostridium difficile infection (CDI) in a subject in need thereof, of claims 1-20 of instant Application.
Conclusion(s):
No claim(s) is allowed at this time.
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/KADE ARIANI/Primary Examiner, Art Unit 1651
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