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 .
DETAILED ACTION
Continued Examination under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission of RCE on January 12, 2026 and amendment after final filed on January 12, 2026 has been entered.
Claims 2, 4, 9-12 were canceled, claim 1 was amended and claims 1, 3, 5-8 are pending in the instant application.
Claims 1, 3, 5-8 are examined on the merits of this office action.
Withdrawn Rejections
The rejection of claims 1, 3, 5-8 under pre-AIA 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under pre-AIA 35 U.S.C. 103(a) as obvious over Shore (World Journal of Urology (2018) 36:801–809, cited previously) is withdrawn in view of amendment of the claims January 12, 2026.
The rejection of claim(s) 1 and 5-8 remain rejected under 35 U.S.C. 103 as being unpatentable over Shore* (The Canadian Journal of Urology, 15(5), published October 2008, page 4291, abstract 2, cited in Applicant’s IDS filed 7/19/2023) in view of Shore (World Journal of Urology (2018) 36:801–809, cited previously) is withdrawn in view of amendment of the claims January 12, 2026.
The rejection of Claims 1, 3, 5-8 on the ground of nonstatutory double patenting as being unpatentable over claims 2, 13-16, 19-20 of copending Application No. 14/606683 (reference application) in view of Shore (World Journal of Urology (Jan 2018) 36:801–809, cited previously) is withdrawn in view of the co-pending Application being abandoned.
Maintained/Revised Rejections
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3, 5-8 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of US Patent No. 10835538 in view of Shore (World Journal of Urology (Jan 2018) 36:801–809, cited previously). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 claims “A method of improving the mean obstructive voiding (claim 1) of mammals having BPH, LUTS comprising (i) identifying and selecting mammals having obstructive voiding symptoms of LUTS wherein the obstructive voiding symptoms are each …straining, weak stream, intermittent stream and incomplete emptying; and (ii) administering to the mammal a therapeutically effective amount of SEQ ID NO: 1 and a carrier, wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%, when compared to administering a control composition that does not contain SEQ IDNO: 1 (Fexapotide Triflutate).” The instant application further claims “wherein method comprises administration of a therapeutically effective amount of SEQ ID NO: 1 as claimed in claim 1 and a carrier” (see claim 1); administered more than once (see claim 3) and “Wherein SEQ ID NO: 1 is administered by intraprostatically” (see claim 1).
US Patent NO:10835538 (referred to as US Patent NO.’538) claims “A method of improving the symptoms of mammals suffering from BPH comprising administering to the mammal a composition comprising a therapeutically effective amount of one or more antibiotics” (see claim 1). US Patent NO: ‘538 further claims “The method of claim 1, further comprising administration of Fexapotide Triflutate and a pharmaceutically acceptable carrier” (see claims 12-13); wherein Fexapotide Triflutate is administered by a route selected from the group consisting of intramuscularly, orally, intravenously, intrathecally, intratumorally, intranasally, topically, and transdermally.” (See claim 13). However, all the examples in the specification of US Patent No. 10835538 teach intraprostatic injection.
US Patent NO:10835538 is silent to claiming treating LUTS including obstructive voiding symptoms with BPH and intraprostatic injection.
However, Shore teaches treating patients with BPH and LUTS including weak stream with 2.5 mg of fexapotide triflutate (FT) which comprises instant SEQ ID NO: 1. Shore teaches that NX02-0017 and NX02-0018 (0017/0018) were randomized, double-blind, parallel group studies designed to demonstrate safety and efficacy of transrectal ultrasound (TRUS) guided intraprostatic FT 2.5 mg in 10 mL phosphate buffered saline (PBS) sterile solution, compared to placebo 10 mL” (see page 802, last paragraph). Shore teaches that FT injection reduced occurrence of Acute urinary retention (see Abstract, purpose and conclusion) and wherein the nocturia (irritative storage symptom) was also improved with FT (see Table 3). Shore teaches treating patients with weak stream (decreasing peak urinary flow rate) and patients with IPSS (lower urinary tract symptoms) and that IPSS was improved.
It would have been obvious before the effective filing date of the claimed invention to treat patients with BPH and lower urinary tract symptoms (one or all) such as straining, weak stream, intermittent stream, incomplete emptying with instant SEQ ID NO: 1. One of ordinary skill in the art would have been motivated to do so given that US Patent No. ‘538 teaches treatment of patients with LUTS and BPH and Shore teaches instant SEQ ID NO: 1 improved IPSS and weak stream in patients with LUTS and BPH.
Furthermore, it would have been obvious before the effective filing date of the claimed invention to practice the method taught by Shore in patients having any one, more than one, or all lower urinary tract symptoms associated with BPH because Shore teaches that LUTS symptoms arise from a common underlying prostatic pathology, namely bladder obstruction caused by prostate enlargement and Shore confirms that intraprostatic administration of NX-1207 improves LUTS and urinary flow in patients exhibiting obstructive features. A person of ordinary skill in the art would have been motivated to identify and select patients presenting with LUTS due to BPH regardless whether the patient exhibited one, several or all of the LUTS symptoms recited in the claims and administer NX-1207 with a reasonable expectation of success, as Shores suggests treatment of severe LUTS and chronic urinary retention and FT treatment was well tolerated and improved IPSS which includes both irritative and obstructive symptoms.
Regarding the functional limitations found in instant claims 1 and 5-8 of “improving the symptoms of mammals having LUTS”; “improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%”; improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 30% to about 150%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 35% to about 125%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 45% to about 105%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, by more than 300%, when compared to the MOVS of patients who received oral medication known to be useful in treating benign prostatic hyperplasia (BPH); the method of US Patent NO. ‘538 teaches the same method of the instant claims including administering the same drug at the same therapeutically effective dose (as defined by Applicant on page see paragraph 0059) and thus, these effects will inherently occur as a result of practicing the method of US Patent NO. ‘538 in view of Shore. Regarding the amount of times to administer FT, this is considered a result effective variable and it would have been obvious to optimize the amount and how often the FT is administered to achieve optimal therapeutic effectiveness. Claims 1-15 of US Patent No. 10835538 in view of Shore are obvious over instant claims 1, 3, 5-8.
Response to Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection (in particular with regards to Shore and not treating LUTS/BPH and all of the symptoms found in instant claim 1). The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
Claims 1, 3, 5-8 are/remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of US Patent No. 10532081 in view of Shore (World Journal of Urology (Jan 2018) 36:801–809). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 claims “A method of improving the mean obstructive voiding (claim 1) of mammals having BPH, LUTS comprising (i) identifying and selecting mammals having obstructive voiding symptoms of LUTS wherein the obstructive voiding symptoms are each …straining, weak stream, intermittent stream and incomplete emptying; and (ii) administering to the mammal a therapeutically effective amount of SEQ ID NO: 1 and a carrier, wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%, when compared to administering a control composition that does not contain SEQ IDNO: 1 (Fexapotide Triflutate).” The instant application further claims “wherein method comprises administration of a therapeutically effective amount of SEQ ID NO: 1 as claimed in claim 1 and a carrier” (see claim 1); administered more than once (see claim 3) and “Wherein SEQ ID NO: 1 is administered by intraprostatically” (see claim 1).
US Patent No. 10532081 claims “A method of ameliorating or preventing the worsening or progression of symptoms of benign prostatic hyperplasia (BPH) in one or more mammals having BPH and showing no increase in International Prostate Symptom Score (IPSS) over time, comprising administering to the one or more mammals a therapeutically effective amount of a peptide comprising the amino acid sequence in SEQ ID NO. 66 (Ile-Asp- Gln-Gln-Val-Leu-Ser-Arg-Ile-Lys-Leu-Glu-Ile-Lys-Arg-Cys-Leu (which is the same as FT as defined by Applicant’s own specification), and when administered to more than one mammal, reducing the percentage of mammals exhibiting worsening or the progression of symptoms of BPH, as measured by the International Prostate Symptom Score (IPSS) by more than 10%, when compared to administering a control.” (see claim 1). US Patent No. 10532081 further claims “The method of claim 1, further comprising administration of FT and a pharmaceutically acceptable carrier” (see claim 2); administering more than once (see claim 3) wherein Fexapotide Triflutate is administered by a route selected from the group consisting of intramuscularly, orally, intravenously, intrathecally, intratumorally, intranasally, topically, intraprostatically, and transdermally.” (see claim 5).
US Patent No. 10532081 is silent to specifically treating LUTS (obstructive voiding symptoms in instant claim 1) and BPH.
The teachings of Shore are provided in the above rejection.
It would have been obvious before the effective filing date of the claimed invention to treat patients with BPH and lower urinary tract symptoms found in instant claim 1 with instant SEQ ID NO: 1. One of ordinary skill in the art would have been motivated to do so given that US Patent No. ‘081 teaches treatment of patients with LUTS and BPH and Shore teaches instant SEQ ID NO: 1 improved IPSS and nocturia in patients with LUTS and BPH.
Furthermore, it would have been obvious before the effective filing date of the claimed invention to practice the method taught by Shore in patients having any one, more than one, or all lower urinary tract symptoms associated with BPH because Shore teaches that LUTS symptoms arise from a common underlying prostatic pathology, namely bladder obstruction caused by prostate enlargement and Shore confirms that intraprostatic administration of NX-1207 improves LUTS and urinary flow in patients exhibiting obstructive features. A person of ordinary skill in the art would have been motivated to identify and select patients presenting with LUTS due to BPH regardless whether the patient exhibited one, several or all of the LUTS symptoms recited in the claims and administer NX-1207 with a reasonable expectation of success, as Shores suggests treatment of severe LUTS and chronic urinary retention and FT treatment was well tolerated and improved IPSS which includes both irritative and obstructive symptoms.
Regarding the functional limitations found in instant claims 1 and 5-8 of “improving the symptoms of mammals having LUTS”; “improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%”; improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 30% to about 150%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 35% to about 125%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 45% to about 105%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, by more than 300%, when compared to the MOVS of patients who received oral medication known to be useful in treating benign prostatic hyperplasia (BPH); the method of US Patent No. 10532081 in view of Shore teaches the same method of the instant claims including administering the same drug at the same therapeutically effective dose (as defined by Applicant on page see paragraph 0059) and thus, these effects will inherently occur as a result of practicing the method of US Patent No. 10532081 in view of Shore.
Claims 1-18 of US Patent No. 10532081 in view of Shore render obvious claims 1, 3, 5-8 of the instant application.
Response to Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection (in particular with regards to Shore and not treating LUTS/BPH and all of the symptoms found in instant claim 1). The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
Claims 1, 3, 5-8 are/remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of US Patent No. 10172910 in view of Shore (World Journal of Urology (Jan 2018) 36:801–809, cited previously). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 claims “A method of improving the mean obstructive voiding (claim 1) of mammals having BPH, LUTS comprising (i) identifying and selecting mammals having obstructive voiding symptoms of LUTS wherein the obstructive voiding symptoms are each …straining, weak stream, intermittent stream and incomplete emptying; and (ii) administering to the mammal a therapeutically effective amount of SEQ ID NO: 1 and a carrier, wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%, when compared to administering a control composition that does not contain SEQ IDNO: 1 (Fexapotide Triflutate).” The instant application further claims “wherein method comprises administration of a therapeutically effective amount of SEQ ID NO: 1 as claimed in claim 1 and a carrier” (see claim 1); administered more than once (see claim 3) and “Wherein SEQ ID NO: 1 is administered by intraprostatically” (see claim 1).
US Patent No. 10172910 claims “A method of preventing or reducing the incidence of acute urinary retention an obstructive symptom of LUTS) in a mammal, comprising administering to the mammal a therapeutically effective amount of a peptide comprising the amino acid sequence in SEQ ID NO. 66 (Ile-Asp- Gln-Gln-Val-Leu-Ser-Arg-Ile-Lys-Leu-Glu-Ile-Lys-Arg-Cys-Leu (which is the same as FT as defined by Applicant’s own specification), and wherein the method reduces the incidence of acute urinary retention.” (See claim 1). US Patent No. 10172910 further claims “The method of claim 1, further comprising administration of the peptide and a pharmaceutically acceptable carrier” (see claim 2); administering more than once (See claim 3) wherein the peptide is administered by a route selected from the group consisting of intramuscularly, orally, intraprostatically” (See claim 4) and more than once (claim 3).
US Patent No. ‘910 is silent to specifically treating LUTS obstructive voiding symptoms with BPH.
The teachings of Shore are provided in the above rejection.
It would have been obvious before the effective filing date of the claimed invention to treat patients with BPH and lower urinary tract symptoms found in instant claim 1 with instant SEQ ID NO: 1. One of ordinary skill in the art would have been motivated to do so given that US Patent No. ‘910 teaches treatment of patients with LUTS and BPH and Shore teaches instant SEQ ID NO: 1 improved IPSS and nocturia in patients with LUTS and BPH.
Furthermore, it would have been obvious before the effective filing date of the claimed invention to practice the method taught by Shore in patients having any one, more than one, or all lower urinary tract symptoms associated with BPH because Shore teaches that LUTS symptoms arise from a common underlying prostatic pathology, namely bladder obstruction caused by prostate enlargement and Shore confirms that intraprostatic administration of NX-1207 improves LUTS and urinary flow in patients exhibiting obstructive features. A person of ordinary skill in the art would have been motivated to identify and select patients presenting with LUTS due to BPH regardless whether the patient exhibited one, several or all of the LUTS symptoms recited in the claims and administer NX-1207 with a reasonable expectation of success, as Shores suggests treatment of severe LUTS and chronic urinary retention and FT treatment was well tolerated and improved IPSS which includes both irritative and obstructive symptoms.
Regarding the functional limitations found in instant claims 1 and 5-12 of “improving the symptoms of mammals having LUTS”; “improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%”; improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 30% to about 150%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 35% to about 125%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 45% to about 105%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, by more than 300%, when compared to the MOVS of patients who received oral medication known to be useful in treating benign prostatic hyperplasia (BPH); the method US Patent No. 10172910 teaches the same method of the instant claims including administering the same drug at the same therapeutically effective dose (as defined by Applicant on page see paragraph 0059) and thus, these effects will inherently occur as a result of practicing the method of US Patent No. 10172910 in view of Shore.
Claims 1-12 of US Patent No. 10172910 in view of Shore render obvious instant Claims 1, 3, 5-8.
Response to Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection (in particular with regards to Shore and not treating LUTS/BPH and all of the symptoms found in instant claim 1). The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
Claims 1, 3, 5-8 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 7, 15-16, 27 of copending Application No. 14/738551 (reference application) in view of Shore (World Journal of Urology (Jan 2018) 36:801–809, cited previously). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 claims “A method of improving the mean obstructive voiding (claim 1) of mammals having BPH, LUTS comprising (i) identifying and selecting mammals having obstructive voiding symptoms of LUTS wherein the obstructive voiding symptoms are each …straining, weak stream, intermittent stream and incomplete emptying; and (ii) administering to the mammal a therapeutically effective amount of SEQ ID NO: 1 and a carrier, wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%, when compared to administering a control composition that does not contain SEQ IDNO: 1 (Fexapotide Triflutate).” The instant application further claims “wherein method comprises administration of a therapeutically effective amount of SEQ ID NO: 1 as claimed in claim 1 and a carrier” (see claim 1); administered more than once (see claim 3) and “Wherein SEQ ID NO: 1 is administered by intraprostatically” (see claim 1).
Co-pending AN 14/738551 claims A method of treating a human having benign prostatic hyperplasia that had not previously received treatment for benign prostatic hyperplasia comprising administering to the human by intraprostatic injection a therapeutically effective amount of an isolated peptide comprising the amino acid sequence in SEQ ID NO. 66 (Ile-Asp-Gln-Gln-Val- Leu-Ser-Arg-Ile-Lys-Leu-Glu-Ile-Lys-Arg-Cys-Leu).” (see claim 1). Co-pending AN 14/738551 further claims “The method of claim 1, further comprising administration of the peptide and a pharmaceutically acceptable carrier” (see claim 1).
Co-pending 14/738551 is silent to specifically treating LUTS including obstructive voiding symptoms and BPH.
However, Shore teaches treating patients with BPH and LUTS including weak stream with 2.5 mg of fexapotide triflutate (FT) which comprises instant SEQ ID NO: 1. Shore teaches that NX02-0017 and NX02-0018 (0017/0018) were randomized, double-blind, parallel group studies designed to demonstrate safety and efficacy of transrectal ultrasound (TRUS) guided intraprostatic FT 2.5 mg in 10 mL phosphate buffered saline (PBS) sterile solution, compared to placebo 10 mL” (see page 802, last paragraph). Shore teaches that FT injection reduced occurrence of Acute urinary retention (see Abstract, purpose and conclusion) and wherein the nocturia (irritative storage symptom) was also improved with FT (see Table 3). Shore teaches treating patients with weak stream (decreasing peak urinary flow rate) and patients with IPSS (lower urinary tract symptoms) and that IPSS was improved.
It would have been obvious before the effective filing date of the claimed invention to treat patients with BPH and lower urinary tract symptoms such as weak stream, incomplete emptying with instant SEQ ID NO: 1. One of ordinary skill in the art would have been motivated to do so given that Co-pending AN 14738551 teaches treatment of patients with LUTS and BPH and Shore teaches instant SEQ ID NO: 1 improved IPSS and nocturia in patients with LUTS and BPH.
Furthermore, it would have been obvious before the effective filing date of the claimed invention to practice the method taught by Shore in patients having any one, more than one, or all lower urinary tract symptoms associated with BPH because Shore teaches that LUTS symptoms arise from a common underlying prostatic pathology, namely bladder obstruction caused by prostate enlargement and Shore confirms that intraprostatic administration of NX-1207 improves LUTS and urinary flow in patients exhibiting obstructive features. A person of ordinary skill in the art would have been motivated to identify and select patients presenting with LUTS due to BPH regardless whether the patient exhibited one, several or all of the LUTS symptoms recited in the claims and administer NX-1207 with a reasonable expectation of success, as Shores suggests treatment of severe LUTS and chronic urinary retention and FT treatment was well tolerated and improved IPSS which includes both irritative and obstructive symptoms.
Regarding the functional limitations found in instant claims 1 and 5-8 of “improving the symptoms of mammals having LUTS”; “improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%”; improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 30% to about 150%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 35% to about 125%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 45% to about 105%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, by more than 300%, when compared to the MOVS of patients who received oral medication known to be useful in treating benign prostatic hyperplasia (BPH);; the method of Co-pending AN 14/738551 teaches administering the same drug, Fexapotide Triflutate, at the same dose, to a patient population that has lower urinary tract symptoms and thus, these effects will inherently occur as a result of practicing the method of Co-pending AN 14/738551 in view of Shore.
Regarding the amount of times to administer FT, this is considered a result effective variable and it would have been obvious to optimize the amount and how often the FT is administered to achieve optimal therapeutic effectiveness.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 4, 7, 15-16, 27 of copending Application No. 14/738551 in view of Shore are obvious over instant claims 1, 3, 5-8.
Response to Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection (in particular with regards to Shore and not treating LUTS). The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
Claims 1, 3, 5-8 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of US Patent No. 12090191 (copending Application No. 17/557951 now US Patent No. 12090191) in view of Shore (World Journal of Urology (Jan 2018) 36:801–809, cited previously). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 claims “A method of improving the mean obstructive voiding (claim 1) of mammals having BPH, LUTS comprising (i) identifying and selecting mammals having obstructive voiding symptoms of LUTS wherein the obstructive voiding symptoms are each …straining, weak stream, intermittent stream and incomplete emptying; and (ii) administering to the mammal a therapeutically effective amount of SEQ ID NO: 1 and a carrier, wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%, when compared to administering a control composition that does not contain SEQ IDNO: 1 (Fexapotide Triflutate).” The instant application further claims “wherein method comprises administration of a therapeutically effective amount of SEQ ID NO: 1 as claimed in claim 1 and a carrier” (see claim 1); administered more than once (see claim 3) and “Wherein SEQ ID NO: 1 is administered by intraprostatically” (see claim 1).
US Patent No. ‘191 claims “A method of enhancing the therapeutic efficacy of Fexapotide Triflutate (FT) in treating Lower Urinary Tract Symptoms (LUTS), comprising a) identifying and selecting patients having irritative or obstructive LUTS: first administering a composition comprising FT to a patient identified and selected in (a) above; and c) subsequently administering a composition comprising FT to the patient at least more than one year after the first administration, wherein the method provides improvements in symptoms of LUTS when compared to patients that were administered the same or twice the total dosage of FT in a single administration.” (see claim 1). US Patent No. ‘191 further The method of claim 1, further comprising administration of the peptide and a pharmaceutically acceptable carrier” (see claim 2); 2.5 mg/l concentration (see claim 3); irritative symptoms (claim 5); multiple administration (see claim 5); treating obstructive symptoms (see claims 8-9); and improvement of symptoms (see claims 12-14). US Patent No. ‘191 is silent to intraprostatic injection and patients with BPH and LUTS. However, Shore teaches treating patients with BPH and LUTS including weak stream with 2.5 mg of fexapotide triflutate (FT) which comprises instant SEQ ID NO: 1. Shore teaches that NX02-0017 and NX02-0018 (0017/0018) were randomized, double-blind, parallel group studies designed to demonstrate safety and efficacy of transrectal ultrasound (TRUS) guided intraprostatic FT 2.5 mg in 10 mL phosphate buffered saline (PBS) sterile solution, compared to placebo 10 mL” (see page 802, last paragraph). Shore teaches that FT injection reduced occurrence of Acute urinary retention (see Abstract, purpose and conclusion) and wherein the nocturia (irritative storage symptom) was also improved with FT (see Table 3). Shore teaches treating patients with weak stream (decreasing peak urinary flow rate) and patients with IPSS (lower urinary tract symptoms) and that IPSS was improved.
It would have been obvious before the effective filing date of the claimed invention to treat patients with BPH and lower urinary tract symptoms such as weak stream, incomplete emptying with instant SEQ ID NO: 1 via intraprostatic injection. One of ordinary skill in the art would have been motivated to do so given that US Patent No. ‘191 teaches treatment of patients with LUTS and BPH and Shore teaches instant SEQ ID NO: 1 improved IPSS and nocturia in patients with LUTS and BPH via intraprostatic injection.
Regarding the functional limitations found in instant claims 1 and 5-8 of “improving the symptoms of mammals having LUTS”; “improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%”; improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 30% to about 150%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 35% to about 125%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 45% to about 105%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, by more than 300%, when compared to the MOVS of patients who received oral medication known to be useful in treating benign prostatic hyperplasia (BPH); the method of US Patent No. ‘191 teaches administering the same drug, Fexapotide Triflutate, at the same dose, to a patient population that has lower urinary tract symptoms and thus , these effects will inherently occur as a result of practicing the method of US Patent No. ‘191. Claims 1-14 of US Patent No. ‘191 are obvious over instant claims 1, 3, 5-8.
Response to Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection (in particular with regards to Shore and not treating LUTS). The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
Claims 1, 3, 5-8 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 18-25 of copending Application No. 18/805214 (reference application) in view of Shore (World Journal of Urology (Jan 2018) 36:801–809, cited previously). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 claims “A method of improving the mean obstructive voiding (claim 1) of mammals having BPH, LUTS comprising (i) identifying and selecting mammals having obstructive voiding symptoms of LUTS wherein the obstructive voiding symptoms are each …straining, weak stream, intermittent stream and incomplete emptying; and (ii) administering to the mammal a therapeutically effective amount of SEQ ID NO: 1 and a carrier, wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%, when compared to administering a control composition that does not contain SEQ IDNO: 1 (Fexapotide Triflutate).” The instant application further claims “wherein method comprises administration of a therapeutically effective amount of SEQ ID NO: 1 as claimed in claim 1 and a carrier” (see claim 1); administered more than once (see claim 3) and “Wherein SEQ ID NO: 1 is administered by intraprostatically” (see claim 1).
Co-pending AN 18/805214 claims “A method of enhancing the therapeutic efficacy of Fexapotide Triflutate (FT) in treating Lower Urinary Tract Symptoms (LUTS), comprising a) identifying and selecting patients having irritative or obstructive LUTS; b) first administering a composition comprising FT to a patient identified and selected in (a) above; and c) subsequently administering a composition comprising FT to the patient at least more than one year after the first administration, wherein the method provides improvements in symptoms of LUTS, when compared to patients that were administered the same or twice the total dosage of FT in a single administration (see claim 1). Co-pending AN 18/805214 further claims a carrier (claim 2); a) identifying and selecting patients having obstructive symptoms of LUTS (claim 10).
Co-pending 18/805214 is silent to specifically treating BPH and all of the LUTS found in instant claim 1 and intraprostatic injection.
However, Shore teaches treating patients with BPH and LUTS including weak stream with 2.5 mg of fexapotide triflutate (FT) which comprises instant SEQ ID NO: 1. Shore teaches that NX02-0017 and NX02-0018 (0017/0018) were randomized, double-blind, parallel group studies designed to demonstrate safety and efficacy of transrectal ultrasound (TRUS) guided intraprostatic FT 2.5 mg in 10 mL phosphate buffered saline (PBS) sterile solution, compared to placebo 10 mL” (see page 802, last paragraph). Shore teaches that FT injection reduced occurrence of Acute urinary retention (see Abstract, purpose and conclusion) and wherein the nocturia (irritative storage symptom) was also improved with FT (see Table 3). Shore teaches treating patients with weak stream (decreasing peak urinary flow rate) and patients with IPSS (lower urinary tract symptoms) and that IPSS was improved.
It would have been obvious before the effective filing date of the claimed invention to treat patients with BPH and lower urinary tract symptoms such as weak stream, incomplete emptying with instant SEQ ID NO: 1. One of ordinary skill in the art would have been motivated to do so given that Co-pending AN 18/805214 teaches treatment of patients with LUTS and BPH and Shore teaches instant SEQ ID NO: 1 improved IPSS and nocturia in patients with LUTS and BPH.
Furthermore, it would have been obvious before the effective filing date of the claimed invention to practice the method taught by Shore in patients having any one, more than one, or all lower urinary tract symptoms associated with BPH because Shore teaches that LUTS symptoms arise from a common underlying prostatic pathology, namely bladder obstruction caused by prostate enlargement and Shore confirms that intraprostatic administration of NX-1207 improves LUTS and urinary flow in patients exhibiting obstructive features. A person of ordinary skill in the art would have been motivated to identify and select patients presenting with LUTS due to BPH regardless whether the patient exhibited one, several or all of the LUTS symptoms recited in the claims and administer NX-1207 with a reasonable expectation of success, as Shores suggests treatment of severe LUTS and chronic urinary retention and FT treatment was well tolerated and improved IPSS which includes both irritative and obstructive symptoms.
Regarding the functional limitations found in instant claims 1 and 5-8 of “improving the symptoms of mammals having LUTS”; “improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%”; improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 30% to about 150%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 35% to about 125%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 45% to about 105%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, by more than 300%, when compared to the MOVS of patients who received oral medication known to be useful in treating benign prostatic hyperplasia (BPH)”; the method of Co-pending AN 18/805214 in view of Shore teaches administering the same drug at the same therapeutically effective dose (as defined by Applicant on page see paragraph 0059) to patients that have lower urinary tract symptoms (and obstructive voiding symptoms) and thus, these effects will inherently occur as a result of practicing the method of Co-pending AN 18/805214 in view of Shore.
Regarding the amount of times to administer FT, this is considered a result effective variable and it would have been obvious to optimize the amount and how often the FT is administered for optimal therapeutic effectiveness.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-17 of copending Application No. 18/805214 (reference application) in view of Shore are obvious over instant claims 1, 3, 5-8.
Response to Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection (in particular with regards to Shore and not treating LUTS). The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
Claims 1, 3, 5-8 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-9, 14 of copending Application No. 18/161922 (reference application) in view of Shore (World Journal of Urology (Jan 2018) 36:801–809, cited previously). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 claims “A method of improving the mean obstructive voiding (claim 1) of mammals having BPH, LUTS comprising (i) identifying and selecting mammals having obstructive voiding symptoms of LUTS wherein the obstructive voiding symptoms are each …straining, weak stream, intermittent stream and incomplete emptying; and (ii) administering to the mammal a therapeutically effective amount of SEQ ID NO: 1 and a carrier, wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%, when compared to administering a control composition that does not contain SEQ IDNO: 1 (Fexapotide Triflutate).” The instant application further claims “wherein method comprises administration of a therapeutically effective amount of SEQ ID NO: 1 as claimed in claim 1 and a carrier” (see claim 1); administered more than once (see claim 3) and “Wherein SEQ ID NO: 1 is administered by intraprostatically” (see claim 1).
Co-pending AN 18/161922 claims “A method of treating a mammal having benign prostatic hyperplasia (BPH) who had not previously taken oral medications for BPH comprising:Identifying mammals having BPH who had not previously taken oral medications for BPH; administering a course of antibiotics to the identified mammals for at least two weeks; administering by intraprostatic injection about 10 ml of a composition comprising about 0.25 mg/ml of FT (instant SEQ ID NO:1)after administering the course of antibiotics; and administering at least once daily from about 0.25 to about 5 mg of a 5 a- reductase inhibitor (5-ARI) and from about 0.25 to about 15 mg of an alpha-adrenergic receptor blocker (alpha blocker) at a period of time from about 2 months to about 4 years after administration of the composition comprising FT. Co-pending 18/161922 is silent to specifically treating BPH and LUTS with obstructive voiding symptoms.
However, Shore teaches treating patients with BPH and LUTS including weak stream with 2.5 mg of fexapotide triflutate (FT) which comprises instant SEQ ID NO: 1. Shore teaches that NX02-0017 and NX02-0018 (0017/0018) were randomized, double-blind, parallel group studies designed to demonstrate safety and efficacy of transrectal ultrasound (TRUS) guided intraprostatic FT 2.5 mg in 10 mL phosphate buffered saline (PBS) sterile solution, compared to placebo 10 mL” (see page 802, last paragraph). Shore teaches that FT injection reduced occurrence of Acute urinary retention (see Abstract, purpose and conclusion) and wherein the nocturia (irritative storage symptom) was also improved with FT (see Table 3). Shore teaches treating patients with weak stream (decreasing peak urinary flow rate) and patients with IPSS (lower urinary tract symptoms) and that IPSS was improved.
It would have been obvious before the effective filing date of the claimed invention to treat patients with BPH and lower urinary tract symptoms such as weak stream, incomplete emptying with instant SEQ ID NO: 1. One of ordinary skill in the art would have been motivated to do so given that Co-pending AN 18/161922 teaches treatment of patients BPH and Shore teaches instant SEQ ID NO: 1 improved IPSS, nocturia in patients with LUTS and BPH.
Furthermore, it would have been obvious before the effective filing date of the claimed invention to practice the method taught by Shore in patients having any one, more than one, or all lower urinary tract symptoms associated with BPH because Shore teaches that LUTS symptoms arise from a common underlying prostatic pathology, namely bladder obstruction caused by prostate enlargement and Shore confirms that intraprostatic administration of NX-1207 improves LUTS and urinary flow in patients exhibiting obstructive features. A person of ordinary skill in the art would have been motivated to identify and select patients presenting with LUTS due to BPH regardless whether the patient exhibited one, several or all of the LUTS symptoms recited in the claims and administer NX-1207 with a reasonable expectation of success, as Shores suggests treatment of severe LUTS and chronic urinary retention and FT treatment was well tolerated and improved IPSS which includes both irritative and obstructive symptoms.
Regarding the functional limitations found in instant claims 1 and 5-8 of “improving the symptoms of mammals having LUTS”; “improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%”; improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 30% to about 150%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 35% to about 125%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 45% to about 105%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, by more than 300%, when compared to the MOVS of patients who received oral medication known to be useful in treating benign prostatic hyperplasia (BPH)”; the method of Co-pending AN 18/161922 in view of Shore teaches administering the same drug at the same therapeutically effective dose (as defined by Applicant on page see paragraph 0059) to patients that have lower urinary tract symptoms (and obstructive voiding symptoms) and thus, these effects will inherently occur as a result of practicing the method of Co-pending AN 18/161922 in view of Shore.
Regarding the amount of times to administer FT, this is considered a result effective variable and it would have been obvious to optimize the amount and how often the FT is administered for optimal therapeutic effectiveness.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 3-9, 14 of copending Application No. 18/161922 (reference application) in view of Shore are obvious over instant claims 1, 3, 5-8
Response to Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection (in particular with regards to Shore and not treating LUTS). The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
New Rejections
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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) 1, 3, 5-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shore (World Journal of Urology (2018) 36:801–809, cited previously) in view of Shore* (The Canadian Journal of Urology, 15(5), published October 2008, page 4291, abstract 2, cited in Applicant’s IDS filed 7/19/2023).
Shore discloses a method improving male lower urinary tract symptoms in patients with benign prostate hyperplasia (see abstract introduction and results) comprising administering Fexapotide triflutate (FT) (which corresponds to instant SEQ ID NO: 1) in PBS ( meeting the limitations of a carrier), wherein the method reduces symptoms of BPH via measurement of IPSS (see abstract, results).
Shore teaches intraprostatic injection (see “patient and Methods” section, lines 1-4). In addition, Shore teaches wherein subjects treated with FT have urinary peak flow rate less than five which is an obstructive voiding symptoms of weak stream (see supplemental figures, table 2, data for the 0017/0018 trials) and BPH. In fact, inclusion criteria for all patients was a Qmax of less than 15 mL/s which is considered abnormal/weaker urinary stream and having BPH for greater than or equal to 1 year (online Table 1, supplement). Table 2 also indicates severe disease due to high baseline BPH symptoms score with an IPSS greater than 20 which would include at least one obstructive or irritative storage symptoms based on the IPSS scoring (incomplete emptying, straining, weak stream and intermittency are obstructive, 4/7 symptoms assessed) and (frequency, nocturia, urgency are irritative, 3/7 symptoms assessed). On a scale of 1-5 of symptoms, a total score of 20 or higher (which includes patients of Shore) would necessarily have at least one obstructive symptoms if not more. Because IPSS is a composite scoring system that assesses the presence and severity of each lower urinary tract symptom, identifying and selecting patients based on IPSS necessarily entails identifying patients having each of the LUTS symptoms recited in the claims, regardless of the relative contribute of any individual symptom.
Shore teaches that patients are identified and selected for treatment based on diagnosis of BPH, international prostate symptom score (IPSS), urinary peak flow rate, and prostate volume, which are all established clinical parameters used to assess lower urinary tract symptoms associated with BPH (see Patients and methods, page 802, statistical methods, page 803). Shore explains that BPH produces lower urinary tract symptoms as a constellation of co-occurring symptoms, including weak urinary stream, staining, intermittency, incomplete emptying, urgency, frequency and nocturia (see introduction, page 801, right column). Shore further teaches use of the IPSS to evaluate presence and severity of LUTS symptoms collectively.
Regarding claims 1 and 3, Shore discloses FT and a carrier (see page 802, left hand column, last paragraph). Shore teaches repeat intraprostatic administration including re-injection of FT (see page 807, left hand column, and second paragraph) meeting the limitations of “more than once).
Shore teaches that NX02-0017 and NX02-0018 (0017/0018) were randomized, double-blind, parallel group studies designed to demonstrate safety and efficacy of transrectal ultrasound (TRUS) guided intraprostatic FT 2.5 mg in 10 mL phosphate buffered saline (PBS) sterile solution, compared to placebo 10 mL” (see page 802, last paragraph). Shore teaches that FT injection reduced occurrence of urinary retention (see Abstract, purpose and conclusion) which is an obstructive voiding symptom and a lower urinary tract symptom. Shore concludes that “The main findings of the 4 studies reported are summarized as follows: 1. LF symptomatic improvement from a single FT treatment under double blind conditions was statistically significant; reduction is surgery long term; reduction in spontaneous AUR and IPSS improvement after single injection FT. FT treatment was considered well tolerated and not painful (see Discussion, page 805 into page 806, paragraphs 1-2). Importantly, Shore suggests treatment of patients with chronic urinary retention and severe LUTS (see page 808, second paragraph, lines 11-14).
Shore* teaches intraprostatic administration of NX-1207 (instant SEQ IDNO:1) to patients having BPH-related LUTS, including patients characterized by reduced urinary peak flow rate (Qmax<15 ml/sec, a standard clinical indicator of weak urinary stream), which is an objective indicator of obstructive voiding symptoms (see Methods, page 4291). Shore* further teaches improvements in IPSS and urinary flow parameters following intraprostatic administration of NX-1207 (see Results, page 4291), confirming treatment directed to the prostate improves LUTS associated with BPH, including obstructive voiding manifestations. Thus, Shore* evidences that, prior to Shore, it was already well understood in the art that intraprostatic administration of NX-1207 to BPH patients presenting with LUTS and obstructive symptoms results in improvement of said urinary symptoms.
Although Shore does not enumerate each individual obstructive voiding symptom in isolation when describing patient selection, Shore teaches that patients were identified and selected for treatment based on established clinical diagnostic criteria for benign prostatic hyperplasia and lower urinary tract symptoms, including International Prostate Symptom Score (IPSS) and urinary peak flow rate (Qmax), which collectively encompass obstructive voiding symptoms such as weak urinary stream, intermittency, and incomplete emptying (see Introduction, page 801; Patients and Methods, pages 802–803; Tables 1–2).
It would have been obvious before the effective filing date of the claimed invention to practice the method taught by Shore in patients having any one, more than one, or all lower urinary tract symptoms associated with BPH because Shore teaches that LUTS symptoms arise from a common underlying prostatic pathology, namely bladder obstruction caused by prostate enlargement and Shore confirms that intraprostatic administration of NX-1207 improves LUTS and urinary flow in patients exhibiting obstructive features. A person of ordinary skill in the art would have been motivated to identify and select patients presenting with LUTS due to BPH regardless whether the patient exhibited one, several or all of the LUTS symptoms recited in the claims and administer NX-1207 with a reasonable expectation of success, as Shores suggests treatment of severe LUTS and chronic urinary retention and FT treatment was well tolerated and improved IPSS which includes both irritative and obstructive symptoms. Furthermore, Shores teaches that enlarged prostate is correlated with and causes diminished urinary flow, bladder hypertrophy, urinary urgency, frequency, nocturia, straining, urinary tract infections, and urinary retention and thus, methods aimed at reducing prostate volume in patients with BPH and specifically obstructive symptoms as stated above, would be therapeutically beneficial (which it is shown to be reduced compared to baseline in the results of Shore).
A person of ordinary skill in the art would have had a reasonable expectation of success in treating patients exhibiting any subset or combination of such symptoms, as Shore demonstrates that treatment directed to the prostate improves lower urinary tract symptoms collectively rather than requiring selection based on any single isolated symptom.
Regarding claims 1, 5-8, shore teaches that change in IPSS from baseline is the primary efficacy endpoint, and reports statistically significant improvement in IPSS following intraprostatic administration of NX-1207 (see Efficacy Results, pages 804-806; Table 2).
Regarding the functional limitations found in claims 1 and 5-8 of “improving the symptoms of mammals having LUTS”; “improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%”; improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 30% to about 150%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 35% to about 125%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 45% to about 105%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, by more than 300%, when compared to the MOVS of patients who received oral medication known to be useful in treating benign prostatic hyperplasia (BPH)”; the method of Shore in view of Shore* teaches the same method of the instant claims including administering the same drug at the same therapeutically effective dose (as defined by Applicant on page see paragraph 0059) to the same patient population (having obstructive voiding symptoms, BPH and LUTS) and thus, these improvements represent expected results of practicing the method taught by Shore when applied to the same patient population using the same clinical assessment tools.
Response to Applicant’s Arguments
Applicant argues “Shore does not disclose identifying and selecting mammals having both BPH and the claimed obstructive voiding symptoms of LUTS, and then administering the claimed peptide only to those identified and selected mammals. The Examiner incorrectly contends, and in direct contrast to sworn testimony by the inventor who has actual personal knowledge of the clinical trials reported in Shore, that: Regarding the limitations of 'identifying the mammals as having BPH and LUTS', assessing IPSS (which includes lower urinary tract symptoms) for the patients prior to administering SEQ IDNO: 1 meets this limitation.
In addition, Shore teaches wherein subjects treated with FT have urinary peak flow rate less than five which is an obstructive voiding symptoms of weak stream (see supplemental figures, table 2, data for the 0017/0018 trials) and BPH. In fact, inclusion criteria for all patients was Qmax of less than 15 mL/s which is considered abnormal/weaker urinary stream and having BPH for greater than or equal to 1 year (online Table 1, supplement) meeting the patient population of the instant claims. Table 2 also indicates severe disease due to high baseline BPH symptoms score with an IPSS greater than 20 which would necessarily include at least one obstructive or irritative storage symptoms based on the IPSS scoring (incomplete emptying, straining, weak stream and intermittency are obstructive, 4/7 symptoms assessed) and (frequency, nocturia, urgency are irritative, 3/7 symptoms assessed).On a scale of 1-5symptoms, a total score of 20 or higher (which includes patients of Shore) would necessarily have at least one obstructive symptoms if not more. Based on the severity of the IPSS of shore and the teachings of weak stream, the patients would necessarily have obstructive voiding symptoms.
The mere fact that certain baseline characteristics of patients enrolled in the clinical trials reported by Shore that were only known and "unblinded" after the trial might show that a very small percentage of those patients may have had BPH and the claimed obstructive voiding symptoms cannot rise to the level of anticipation. Indeed, the data from Shore, including the additional on-line data, show quite clearly that patients with severe BPH and with very few who had low Qmax values were administered both FT and the control. This alone refutes any conclusion that the claims are anticipated because the claims require the identification and selection of mammals having both BPH and the claimed obstructive voiding symptoms of LUTS, and then administering FT only to those mammals that were selected.
Shore does not disclose that the data presented in supplemental table 2 of Shore, which identifies certain characteristics of patients treated in the clinical trials, was collected and measured prior to administration of FT, and that the individuals administering FT in the clinical trials knew these characteristics prior to administration. In fact, they could not possibly know of these characteristics because the trials were double blinded FDA-approved trials. The investigators did not know any of the specific characteristics of the patients, such as whether they had a low urinary peak flow rate, or whether they had an IPSS above 20. Rather, all the investigators knew prior to administration of either FT or placebo (they did not know whether a placebo or FT were being administered), was that the patients met the criteria for inclusion in the trials, and did not meet the exclusion criteria.
As the Examiner noted, one of the inclusion criteria for the trials discussed in Shore was a Qmax <15 mL/sec. While this level is sometimes indicative of an issue, the normal Qmax for men ranges from 10-20 mL/sec, and a flowrate below 10 mL/sec is an indicator of some form of obstruction, or a weak bladder. It is not, by itself, an indication that the subject has LUTS, much less each of the claimed obstructive voiding symptoms of LUTS. The specification (paragraph [0003]) discusses Park, H.J., et al.,"Urinary Tract Symptoms (LUTS) Secondary to Benign Prostatic Hyperplasia (BPH).,World J. MensHealth,No. 31(3), 193-207 (2013), previously submitted. Park describes the diagnoses a mammal with LUTS/BPH as follows: Clinical diagnosis of LUTS/BPH is a multistep process used to eliminate prostate cancer, identify risk factors, and obtain physiological measures.
Symptoms of LUTS/BPH are generally assessed using the International Prostate Symptom Score (IPSS) or AUA Prostate Symptom Index (AUA- SI); a transrectal ultrasound of the prostate; the measurement of the maximal urinary flow rate (Omax) assessed by uroflowmetry; and the
measurement of postvoid residual volume assessed by ultrasound, urinalysis, and serum prostate specific antigen (PSA) levels. Park at 194, right hand column, third full paragraph. These factors are all taken into consideration, and not any single one, including measurement of Qmax, as well as postvoid residual volume, which is recited by the claims as "incomplete emptying. ‘And while Shore 2018 notes that a Qmax <15 mL/sec is an inclusion criteria (an inclusion criteria not indicative, by itself, of obstructive symptoms), Shore 2018also states that exclusion criteria for the clinical trials were a post-void residual urine volume > 200 ml, (incomplete emptying") and urinary retention (claimed as "straining"). Thus, the patients treated in the clinical trials discussed by Shore 2018 could not have had each of the claimed obstructive symptoms of LUTS because they were expressly excluded.
This evidence, when coupled with the declaration submitted in this application on July 6, 2023,("Declaration") compels the conclusion that Shore 2018 does not disclose, inherently or otherwise, "identifying and selecting mammals having both BPH and obstructive voiding symptoms of LUTS wherein the obstructive voiding symptoms of LUTS are each of straining, weak stream, intermittent stream, and incomplete emptying, as required by the claims. As the Examiner may recall, the present inventor testified without equivocation that "Shore does not disclose administering FT to patients identified as having obstructive voiding symptoms of LUTS. Declaration at 8. The inventor further testified that "no patients were specifically enrolled based on any specific criteria identified as having obstructive voiding symptoms of LUTS." These statements, along with the exclusion criteria published by Shore 2018,are evidence that the Patent Office cannot ignore, and they prove very clearly that no patient involved in the trials reported by Shore 2018 were identified and selected as having both BPH and the claimed obstructive voiding symptoms of LUTS, much less then administered the claimed FT. Shore 2018 therefore cannot anticipate the claims.
The Action states that "Shore teaches administering the same drug to patients with BPH and obstructive voiding symptoms of LUTS."As stated above, Shore does not teach administration of the same drug to patients with the claimed obstructive voiding symptoms of LUTS, and in fact expressly states that patient with obstructive voiding symptoms (postvoid residual volume >200 mL and urinary retention) were excluded and therefore NOT treated. The Action also appears to focus on a subject having just one voiding symptom of LUTS, and thus would fall within the scope of the patients identified by the claims. As stated in in applicant's specification, referencing inter alia, the Park document, identifying or diagnosing a patient as having LUTS, and more specifically obstructive LUTS, means that patient has each of the obstructive symptoms recited by the claims, not just one of them. For example, a patient could have a low Qmax, (e.g., lower than 10 mL/s), but not suffer from straining, intermittent stream, or incomplete emptying. This patient would not be identified as having the claimed obstructive symptoms of LUTS, and may not find a low Qmax bothersome to the point of seeking medical intervention.
To establish inherent anticipation, the Examiner must show that the patients of Shore necessarily were not only identified and selected as having both BPH and the claimed obstructive voiding symptoms of LUTS, but then only those patients were administered the claimed active ingredient. The Examiner has not shown this, but rather has only asserted (not shown with evidence) that some patients, not all of them, had BPH and perhaps one (or even more) obstructive voiding symptom of LUTS prior to the trial. Even if that were true, they were not selected out of all of the patients enrolled in the trial, nor were they necessarily administered the claimed FT because about half received FT and half received the control, as required in any double blinded clinical trial.
Inherency "is appropriate only when the reference discloses prior art that must necessarily include the unstated limitation.."TranscleanCorp.v.BridgewoodSears., Inc., 290 F.3d 1364, 1373 (Fed. Cir. 2002) (emphasis in original); Schering Corp. v.GenevaPharraceuticals, 339 F.3d 1373, 1377 (Fed. Cir. 2003). The prior art reference itself need not describe an inherent characteristic or feature of the invention. However, inherency may not be established by probabilities or possibilities. In re Robertson, 169 F.3d 743, 745 (Fed. Cir. 1999)(citations omitted)("the mere fact that a certain thing may result from a given set of circumstances is not sufficient.").
Shore also discloses that a majority of patients had IPSS scores above 20, and the Examiner appears to take the position that this means they inherently had one obstructive voiding symptom. As noted above, however, this is insufficient to establish that the subject was identified as having obstructive LUTS, as required by the claims. If they do not necessarily have the claimed obstructive voiding symptoms, then Shore cannot inherently disclose identifying such patients, much less administering FT only to those patients.
Even if a skilled artisan could have identified and treated patients having the claimed obstructive voiding symptoms of LUTS, such identification and treatment is not disclosed by Shore, and theoretically could represent one of numerous possibilities disclosed therein. Consistent with the legal precedent discussed above, it is improper to rely on inherency when the inherent element is not necessarily present in the prior art, as is the case here. If there were some unknown overlap between the patients of Shore and those recited by the present claims, Shore does not necessarily identify and treat the same patient population. As a consequence, the claimed method, along with the claimed improvements cannot be inherent.
With respect to obviousness, the Examiner notes that Shore does not include the specific efficacy data regarding MOVS, but contends "it would have been obvious to a person of ordinary skill in the art to expect that treating EPH with the disclosed drug would result in improvement of obstructive voiding symptoms of LUTS, as these symptoms are well known clinical manifestations of EPH and are caused by BPH."Action at 13. This conclusion is directly refuted by the evidence in the present application that shows very clearly that medications known to treat BPH (conventional oral medications, which are widely used throughout the world), are actually worse than the placebo control in reducing MOVS. The specification states at paragraph [0041]: The inventor discovered that the administration of conventional BPH oral medications to patients having LUTS exhibited a dramatic decrease in mean obstructive voiding symptoms(MOVS)measured by IPSS, and in mean irritative storage symptoms (MISS) measured IPSS, when compared to patients who received only placebo. The inventors discovered that the
PNG
media_image1.png
14
6
media_image1.png
Greyscale
decrease in moves was about 50%and the decrease in MISS was about 40%Accordingly conventional therapies for treating BPH would not have been expected to improve, symptoms of patients having LUTS thereby making the dramatic improvement realized by the present invention that includes administration of FT even more unexpected. Example 2, Table 2 shows that conventional oral medications only reduced MOVS by about 1.14, whereas the control reduced MOVS by almost double that amount (2.35). In other words, the control was almost twice as effective in reducing MOVS than conventional BPH medications.
As shown in the examples, and described in Dr. Averback's declaration (previously filed), known EPH medications actually provided a lower improvement in MOVS when compared to the control, whereas treatment with the claimed peptide provided a dramatic increased improvement. Averback Declaration at paras. 14-15. These known conventional BPH medications were approved by the FDA for showing an improvement in total IPSS scores when compared to a control, but yet the inventor discovered that these same conventional BPH medications that improved total IPSS scores, actually were less effective than the control in improving MOVS. This is entirely surprising and unexpected. Dr. Averback concluded: Because FT had previously been reported to be effective in treating BPH, and because known BPH therapies (e.g., conventional oral medication - see Example 2 above) were found not effective in treating either irritative or obstructive symptoms in this controlled study under the same conditions, there would have been no reason to expect that administration of FT would have specifically and significantly improved improved the obstructive voiding symptoms in patients with LUTS, much less a greater than 300% improvement, ((4.80-1.14/1.14) times 100%), when compared to other known BPH therapies. Declaration submitted July 6, 2023, at 15. Prior to the filing date of this application, a person having ordinary skill in the art would not have expected a BPH therapy to be effective in reducing MOVS, and certainly could not have expected the incredibly improved reduction in MOVS achieved by the claimed peptide.
The improvements recited by the claims therefore cannot be inherent, or expected in Shore because Shore clearly teaches a different patient population, and expressly excludes patients having the claimed obstructive voiding symptoms. Again, even if some of the patients discussed in Shore had one obstructive voiding symptom of LUTS and were then administered the claimed peptide, Shore discloses administering the claimed peptide to all BPH patients, not just the select few that had severe BPH (IPSS >20),or peak urinary flow rates below 5. This is not the same method recited by the claims - Shore does not disclose or suggest administering the same drug to the same patient population. See Averback Declaration filed July 6, 2023, at para. 8. The Examiner has not established that the methods are the same, whereas applicant has presented evidence that they are not the same. And because they are not the same method (administering claimed peptide to a different patient population), the effects recited by the claims cannot be inherent.
The mean obstructive voiding symptom score represents the mean of the sum of the scores of IPSS items 1, 3, 5, and 6, where the mean is the mean of the patient population. Acute urinary retention is not any of the IPSS items 1, 3, 5, and 6. /d at 12. Shore does not disclose or suggest improving the mean obstructive voiding scores. For example, treating a patient with BPH could result in a significant improvement in total IPSS score due to improvement in other (not obstructive) symptoms and could also reduce the incidence of AUR, or nocturia (as disclosed by Shore), but have no improvement in MOVS. Id. This is evident from the data in the specification showing that conventional BPH medications, all known to show an improvement in total IPSS scores, actually showed a dramatically lower improvement in MOVS when compared to the control, and when compared to the claimed peptide. The inventor testifies that: "a person having ordinary skill in the art would understand that Shore does not disclose or suggest an improvement in MOVS."/d'. The inventor further testifies: It is my opinion that a person having ordinary skill in the art would not have anticipated or otherwise known or expected, either prior to the clinical trials, or after the Shore publication, that obstructive voiding symptoms were a meaningful sub-species of LUTS, or LUTS due to BPH. The data presented in my application shows the surprising and unanticipated out-sized benefit of FT in treating obstructive voiding symptoms. The clinical trials were not designed or planned to show this benefit. Rather, it was a surprising and unexpected finding made after the trials.
It is clear that the claims recite identifying and treating a specific group of patients that was not recognized by Shore. Applicant has provided sufficient evidence to show the surprising and unexpected effects of the claimed invention. Applicant also has presented sufficient evidence to rebut the Examiner's statements regarding Shore's disclosure being adequate to anticipate and/or render obvious the present claims. Accordingly, applicant respectfully requests that the Examiner reconsider and withdraw this rejection. The poster presentation of Shore* discloses that "85 men with BPH-related LUTS were enrolled from32 clinical sites," but does not disclose or suggest that these men were identified as having both BPH and each of the claimed obstructive voiding symptoms of LUTS. Even combined with Shore and assuming the use of a carrier were obvious or inherent in Shore*, the disclosure of Shore* in view of Shore does not render obvious the claims for the same reasons discussed above.
The inventor unexpectedly discovered that treating the claimed patients resulted in a dramatic and unexpected improvement in mean obstructive voiding symptom scores (MOVS), but that conventional oral medications have the opposite effect and have a far lower improvement in MOVS when compared to a control. While conventional oral medications such as alpha blockers and 5o- reductase inhibitors have been reported as useful in treating certain symptoms of LUTS, they are not effective in improving MOVS, but yet the claimed peptide was highly effective in improving MOVS, when each were compared to the same control. These results are not disclosed or suggested, and cannot be inherent, in either Shore*or Shore. Accordingly, applicant respectfully submits that the combination of Shore* and Shore would not have rendered obvious the claims, and kindly asks that the Examiner reconsider and withdraw this rejection.
Applicants arguments have been fully considered but not found persuasive. Applicant argues that Shore does not disclose “identifying and selecting mammals having both BPH and the claimed obstructive voiding symptoms of LUTS” because Shore does not expressly enumerate each obstructive symptom individually and because the clinical trials were double blinded. This argument improperly narrows the scope of the claims. The claims recite identifying and selecting mammals having BPH and obstructive voiding symptoms of LUTS, but do not require separate individualized identification of each obstructive symptom is isolate, nor do they require that the administering clinician subjectively know or record each symptom prior to administration. Shore teaches identification and selection of patients based on established clinical diagnostic criteria for BPH-related LUTS, including IPSS and urinary peak flow rate (Qmax) (see introduction, page 801; patients and methods, 802-803). These clinical parameters are routinely used to assess LUTS and collectively encompass obstructive voiding symptoms, including weak urinary stream, intermittency, straining, and incomplete emptying. Accordingly, Shore teaches identifying and selecting patients presenting with LUTS having obstructive manifestations within the scope of the claims. The double blind nature of the clinical trials does not negate patient identification or selection. Enrollment based on predefined diagnostic inclusion criteria necessarily requires assessment of IPSS and Qmax prior to administration of treatment. The claims do not require the investigators administering the treatment be aware of each symptom, only that the method include identifying and selecting patients having the recited condition.
Applicant further argues that Shore expressly excludes patients having obstructive voiding symptoms because certain exclusion criteria (e.g. extreme post void residual volume or acute urinary retention were applied). Applicants arguments have been considered but not found persuasive. Shores exclusion of patients with extreme or severe manifestations of urinary obstruction does not establish that enrolled patients lacked obstructive voiding symptoms altogether. Obstructive LUTS exist on a continuum of severity. Shore expressly documents reduced urinary peak flow rates and elevated IPSS scores in enrolled patients, both of which are objective indicators of obstructive voiding symptoms. Exclusion of extreme cases does not negate the presence of obstructive manifestations in the treatment population or teach away from treating patients with these symptoms (see MPEP 2144.05).
Applicant further argues that the claims require identification of patients having each obstructive voiding symptom and that Shore does not disclose such a population. Applicants arguments have been considered but not found persuasive. While Shore does not expressly state that patients were identified as having each of straining, weak stream, intermittent stream, and incomplete emptying, Shore teaches that LUTS due to BPH is a constellation of co occurring obstructive symptoms arising from a common underlying pathology, namely bladder outlet obstruction due to prostate enlargement. Shore further teaches that patients enrolled had severe LUTS as measure by IPSS and reduced urinary flow, which are objective indicators of obstructive voiding dysfunction.
As stated in the above rejection, it would have been obvious before the effective filing date of the claimed invention to practice the method taught by Shore in patients having any one, more than one, or all lower urinary tract symptoms associated with BPH because Shore teaches that LUTS symptoms arise from a common underlying prostatic pathology, namely bladder obstruction caused by prostate enlargement and Shore confirms that intraprostatic administration of NX-1207 improves LUTS and urinary flow in patients exhibiting obstructive features. A person of ordinary skill in the art would have been motivated to identify and select patients presenting with LUTS due to BPH regardless whether the patient exhibited one, several or all of the LUTS symptoms recited in the claims and administer NX-1207 with a reasonable expectation of success, as Shores suggests treatment of severe LUTS and chronic urinary retention and FT treatment was well tolerated and improved IPSS which includes both irritative and obstructive symptoms. Furthermore, Shores teaches that enlarged prostate is correlated with and causes diminished urinary flow, bladder hypertrophy, urinary urgency, frequency, nocturia, straining, urinary tract infections, and urinary retention and thus, methods aimed at reducing prostate volume in patients with BPH and specifically obstructive symptoms as stated above, would be therapeutically beneficial (which it is shown to be reduced compared to baseline in the results of Shore).
A person of ordinary skill in the art would have had a reasonable expectation of success in treating patients exhibiting any subset or combination of such symptoms, as Shore demonstrates that treatment directed to the prostate improves lower urinary tract symptoms collectively rather than requiring selection based on any single isolated symptom.
Applicant argues that Shore does not disclose or suggest improvement in mean obstructive voiding symptom scores (MOVS), and therefore does not render the claims anticipated or obvious.
Applicants arguments have been considered but not found persuasive. The claims do not require that Shore expressly label or report MOVS as a distinct endpoint. MOVS represents a calculation derived from IPSS subscores corresponding to obstructive symptoms. Shore teaches statistically significant improvement in IPSS following intraprostatic administration of fexapotide triflutate. Improvement in obstructive IPSS subscores is an expected result of improving IPSS overall and does not require separate disclosure as a named metric.
Differences in degree of improvement or post-hoc analyses of subcomponents do not render the claimed method patentably distinct where the prior art teaches treatment of the same condition using the same method. As stated above, Regarding the functional limitations found in claims 1 and 5-8 of “improving the symptoms of mammals having LUTS”; “improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%”; improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 30% to about 150%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 35% to about 125%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 45% to about 105%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, by more than 300%, when compared to the MOVS of patients who received oral medication known to be useful in treating benign prostatic hyperplasia (BPH); the method of Shore teaches the same method of the instant claims including administering the same drug at the same therapeutically effective dose (as defined by Applicant on page see paragraph 0059) to the same patient population (having obstructive voiding symptoms, BPH and LUTS) and thus, these improvements represent expected results of practicing the method taught by Shore when applied to the same patient population using the same clinical assessment tools.
Applicant further relies heavily on inventor testimony asserting that Shore does not disclose treatment of patients identified as having obstructive voiding symptoms. However, this cannot overcome or negate the express teachings of the prior art reference itself. Shore’s disclosure regarding patient selection criteria, diagnostic assessment, and treatment outcomes governs, regardless of inventor characterization.
Applicant argues that a person of ordinary skill would not have expected treatment of BPH to improve obstructive voiding symptoms.
Applicants arguments have been fully considered but not found persuasive. This assertion is contradicted by Shore, which teaches that LUTS associated with BPH arise from a common underlying prostatic pathology and reports improvement in urinary flow parameters and symptom scores following intraprostatic treatment. A person of ordinary skill in the art would have been motivated to treat patients exhibiting any subset or combination of LUTS symptoms associated with BPH, including obstructive voiding manifestations, with a reasonable expectation of success (see revised rejection above).
Applicant argues that the claimed improvement in mean obstructive voiding symptoms (MOVS) constitutes a surprising and unexpected result because conventional oral BPH therapies allegedly do not improve, and may worsen, MOVS. Applicant’s evidence of alleged unexpected results has been considered but is not commensurate in scope with the claims.
Shore teaches that intraprostatic administration of NX-1207 to patients with BPH-related LUTS results in statistically significant improvement in urinary symptoms as measured by the International Prostate Symptom Score (IPSS), as well as improvement in urinary flow parameters. The IPSS is a validated clinical instrument that evaluates both irritative and obstructive voiding symptoms, including weak stream, intermittency, straining, and incomplete emptying. Thus, improvement in obstructive voiding symptoms is encompassed within Shore’s reported improvement in IPSS and urinary flow.
Applicant’s evidence comparing the claimed peptide to conventional oral BPH therapies does not rebut the Examiner’s prima facie case because Shore does not rely on, nor suggest equivalence with, conventional oral therapies. Rather, Shore teaches a different treatment modality, direct intraprostatic administration, directed at the prostate itself, and reports clinically meaningful improvements in LUTS severity and urinary flow. A person of ordinary skill in the art would have reasonably expected that reducing prostatic pathology through intraprostatic treatment would improve obstructive manifestations of LUTS associated with BPH.
Further, Applicant’s evidence does not demonstrate that improvement in obstructive voiding symptoms was unexpected relative to Shore’s teachings. Shore expressly teaches treatment of patients exhibiting obstructive features, including reduced urinary peak flow and elevated baseline IPSS, and reports improvement following treatment. The fact that Shore did not separately label or numerically report a “MOVS” value does not negate the reasonable expectation that obstructive voiding symptoms assessed within the IPSS framework would improve as part of the overall symptomatic improvement disclosed.
Additionally, Applicant’s alleged unexpected results are not commensurate in scope with the claims. The claims broadly encompass identifying and treating mammals having BPH and obstructive voiding symptoms and administering SEQ ID NO:1 by intraprostatic injection, without limitation to patients previously treated with or refractory to conventional oral medications. Evidence limited to comparisons against oral therapies under specific study conditions does not establish that the claimed method produces unexpected results across the full scope of the claimed patient population.
Accordingly, Applicant’s evidence of unexpected results does not outweigh the strong evidence provided by Shore that intraprostatic administration of NX-1207 to BPH patients with LUTS would reasonably be expected to improve obstructive voiding symptoms.
Taken together, Applicant’s arguments rely on improper claim narrowing, mischaracterization of Shore’s disclosures, and an incorrect application of inherency and expectation principles. Shore teaches identifying and selecting patients with BPH-related LUTS using established clinical criteria and treating such patients with fexapotide triflutate, resulting in improvement of LUTS, including obstructive voiding manifestations. Accordingly, the rejections under 35 U.S.C. §103 are maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3, 5-8 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of US Patent No. 11628202 in view of Shore (World Journal of Urology (Jan 2018) 36:801–809, cited previously). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 claims “A method of improving the mean obstructive voiding (claim 1) of mammals having BPH, LUTS comprising (i) identifying and selecting mammals having obstructive voiding symptoms of LUTS wherein the obstructive voiding symptoms are each …straining, weak stream, intermittent stream and incomplete emptying; and (ii) administering to the mammal a therapeutically effective amount of SEQ ID NO: 1 and a carrier, wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%, when compared to administering a control composition that does not contain SEQ IDNO: 1 (Fexapotide Triflutate).” The instant application further claims “wherein method comprises administration of a therapeutically effective amount of SEQ ID NO: 1 as claimed in claim 1 and a carrier” (see claim 1); administered more than once (see claim 3) and “Wherein SEQ ID NO: 1 is administered by intraprostatically” (see claim 1).
US Patent NO:11628202 (referred to as US Patent NO.’202) claims “A method of reducing the need for subsequent invasive surgical intervention in treatment naïve humans having benign prostatic hyperplasia (BPH) who had not previously taken an additional active agent for BPH, comprising: (a) selecting treatment naïve humans having BPH who had not previously taken an additional active agent; and (b) administering to the treatment naïve human about 2.5 mg of an isolated peptide consisting of the amino acid sequence in SEQ ID NO. 66 (Ile-Asp-Gln-Gln-Val-Leu-Ser-Arg-Ile-Lys-Leu-Gludle-Lys-Arg-Cys-Leu) to reduce invasive surgical procedures within 2 years from administration by an amount within the range of from about 75 to 95%, when compared to treatment naïve humans having BPH receiving a placebo.US Patent NO:10835538 is silent to claiming treating LUTS including obstructive voiding symptoms with BPH and intraprostatic injection” (see claim 1). US Patent NO:11628202 further claims the peptide with a carrier (see claim 2).
US Patent NO:11628202 is silent to treating patients with LUTS and BPH, including the obstructive voiding symptoms found in instant claim 1.
However, Shore teaches treating patients with BPH and LUTS including weak stream with 2.5 mg of fexapotide triflutate (FT) which comprises instant SEQ ID NO: 1. Shore teaches that NX02-0017 and NX02-0018 (0017/0018) were randomized, double-blind, parallel group studies designed to demonstrate safety and efficacy of transrectal ultrasound (TRUS) guided intraprostatic FT 2.5 mg in 10 mL phosphate buffered saline (PBS) sterile solution, compared to placebo 10 mL” (see page 802, last paragraph). Shore teaches that FT injection reduced occurrence of Acute urinary retention (see Abstract, purpose and conclusion) and wherein the nocturia (irritative storage symptom) was also improved with FT (see Table 3). Shore teaches treating patients with weak stream (decreasing peak urinary flow rate) and patients with IPSS (lower urinary tract symptoms) and that IPSS was improved.
It would have been obvious before the effective filing date of the claimed invention to treat patients with BPH and lower urinary tract symptoms (one or all) such as straining, weak stream, intermittent stream, incomplete emptying with instant SEQ ID NO: 1. One of ordinary skill in the art would have been motivated to do so given that US Patent No. ‘202 teaches treatment of patients with BPH and Shore teaches instant SEQ ID NO: 1 (same as SEQ ID NO:66) improved IPSS and weak stream in patients with LUTS and BPH.
Furthermore, it would have been obvious before the effective filing date of the claimed invention to practice the method taught by Shore in patients having any one, more than one, or all lower urinary tract symptoms associated with BPH because Shore teaches that LUTS symptoms arise from a common underlying prostatic pathology, namely bladder obstruction caused by prostate enlargement and Shore confirms that intraprostatic administration of NX-1207 improves LUTS and urinary flow in patients exhibiting obstructive features. A person of ordinary skill in the art would have been motivated to identify and select patients presenting with LUTS due to BPH regardless whether the patient exhibited one, several or all of the LUTS symptoms recited in the claims and administer NX-1207 with a reasonable expectation of success, as Shores suggests treatment of severe LUTS and chronic urinary retention and FT treatment was well tolerated and improved IPSS which includes both irritative and obstructive symptoms.
Regarding the functional limitations found in instant claims 1 and 5-8 of “improving the symptoms of mammals having LUTS”; “improves the mean obstructive voiding symptoms (MOVS) measured by the International Prostate Symptom Score (IPSS), by more than 30%”; improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 30% to about 150%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 35% to about 125%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, within the range of from about 45% to about 105%; wherein the method improves the mean obstructive voiding symptoms (MOVS) measured by IPSS, by more than 300%, when compared to the MOVS of patients who received oral medication known to be useful in treating benign prostatic hyperplasia (BPH); the method of US Patent NO. ‘538 teaches the same method of the instant claims including administering the same drug at the same therapeutically effective dose (as defined by Applicant on page see paragraph 0059) and thus, these effects will inherently occur as a result of practicing the method of US Patent NO. ‘538 in view of Shore. Regarding the amount of times to administer FT, this is considered a result effective variable and it would have been obvious to optimize the amount and how often the FT is administered to achieve optimal therapeutic effectiveness. Claims 1-15 of US Patent No. 10835538 in view of Shore are obvious over instant claims 1, 3, 5-8.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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, Lianko Garyu can be reached at 571-270-7367. 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.
/ERINNE R DABKOWSKI/ Examiner, Art Unit 1654