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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on 12/12/2025 has been entered.
DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claim filed on 12/12/2025 is acknowledged.
3. Claims 1-7 have been cancelled.
4. New claims 23 and 24 have been added.
5. Claims 8-24 are pending in this application.
6. Claims 8-10, 12, 17 and 19 remain withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Claims 13, 15, 18 and 22 remain withdrawn from consideration as being drawn to non-elected species.
7. Applicant elected without traverse of Group 3 (claims 11, 13-16 and 18) and elected without traverse PDE11 inhibitor BC11-38 (without a GUCY2C agonist) as species of agent to be administered; and stage 1 4 Parkinson's disease as species of individual in the reply filed on 1/11/2024. Since there appears to be a typo in the elected species of individual, the Examiner telephoned Applicant’s representative, Michael N. Mercanti, on 2/2/2024 for clarification. Applicant’s representative states on the phone that stage 1 Parkinson's disease as the elected species of individual (see PTO-413 dated 2/8/2024).
Restriction requirement was deemed proper and made FINAL in the previous office actions. Group 3 is drawn to a method of treating an individual in need thereof that has Parkinson’s disease characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra, the method comprising administering a selective phosphodiesterase (PDE) 11 inhibitor or a combination of a selective PDE11 inhibitor and a PDE2 inhibitor to the individual, in a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10%; and/or administering a phosphodiesterase (PDE) 11 inhibitor or a combination of a PDE11 and a PDE2 inhibitor to the individual, in a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10%, wherein the PDE11 inhibitor has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs. A search was conducted on the elected species; and prior art was found. Claims 13, 15, 18 and 22 remain withdrawn from consideration as being drawn to non-elected species. Claims 11, 14 , 16, 20, 21, 23 and 24 are examined on the merits in this office action.
35 U.S.C. § 112 paragraph (f)
8. The following is a quotation of 35 U.S.C. 112(f):
(f) ELEMENT IN CLAIM FOR A COMBINATION.—An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
9. This application includes one or more claim limitations that do not use the word "means," but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: the limitation “a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10%” recited in instant claims 11 and 21. Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof. If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
New Rejections
Claim Rejections - 35 U.S.C. § 112 paragraph (b)
10. The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
11. Claims 11, 14 , 16, 20, 21, 23 and 24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
12. Claims 11 and 21 recite the limitation “a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10%”. As stated in Section 9 above, such limitation invokes 35 U.S.C. § 112 paragraph (f). However, the instant specification fails to disclose any structure, material or acts for performing the recited function. Furthermore, in the instant case, it is unclear how to determine the dopamine production in a dopaminergic cell in the substantia nigra in the treated individual. Taken all these together, the metes and bounds of instant claims 11 and 21 are vague and indefinite. Because claims 14, 16, 20, 23 and 24 depend from indefinite claim 11 or 21 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
Furthermore, for the purpose of this examination and in the broadest reasonable interpretation, the Examiner is interpretating treating the instant claimed individual with either a selective PDE11 inhibitor or a combination of a selective PDE11 inhibitor and a PDE2 inhibitor would inherently result in a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10% recited in instant claims 11 and 21. Such interpretation applies to all the rejections set forth below.
Maintained/Revised Rejections
Claim Rejections - 35 U.S.C. § 103
13. 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 of this title, 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.
14. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
15. (Revised due to Applicant’s amendment to the claim) Claims 11, 14, 16, 20, 21, 23 and 24 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Hendrick et al (WO 2015/106032 A1, filed with IDS), and as evidenced by Kalia et al (Lancet, 2015, 386, pages 896-912), and in view of Ceyhan et al (Chemistry & Biology, 2012, 19, pages 155-163, filed with IDS), Stocchi et al (Translational Neurodegeneration, 2015, pages 1-7, cited and enclosed in the previous office actions) and the Stages of Parkinson’s Disease document (PRO NEWSWORTHY NOTES, 2002, pages 1-2, cited and enclosed in the previous office actions).
The instant claims 11, 14, 16, 20, 21, 23 and 24 are drawn to a method of treating an individual in need thereof that has Parkinson’s disease characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra, the method comprising administering a selective phosphodiesterase (PDE) 11 inhibitor or a combination of a selective PDE11 inhibitor and a PDE2 inhibitor to the individual, in a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10%; and/or administering a phosphodiesterase (PDE) 11 inhibitor or a combination of a PDE11 and a PDE2 inhibitor to the individual, in a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10%, wherein the PDE11 inhibitor has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs.
Please note: As stated in Section 12 above, in the instant case, the Examiner is interpretating treating the instant claimed individual with either a selective PDE11 inhibitor or a combination of a selective PDE11 inhibitor and a PDE2 inhibitor would inherently result in a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10% recited in instant claims 11 and 21.
Hendrick et al, throughout the patent, teach both PDE1 and PDE2 are PDE that hydrolyzes both cAMP and cGMP; a product comprising a PDE1 inhibitor and a PDE2 inhibitor, in free or salt form; pharmaceutical compositions comprising such product; and a method of treating an individual has cAMP and/or cGMP related disorders, wherein the method comprises administering such product to said individual, and wherein the cAMP and/or cGMP related disorder can be Parkinson's disease, for example, Abstract; page 1, paragraphs [0002] and [0003]; page 3, paragraph [0007]; pages 5-6, paragraph [0014]; page 13, paragraphs [0032] and [0033]; and claims 10, 11, 14 and 15. And as evidenced by Kalia et al, Parkinson’s disease is characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra (see for example, Abstract; and page 896, Section “Introduction”). It meets the limitation of “an individual in need thereof that has Parkinson’s disease characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra” recited in instant claims 11 and 21.
The difference between the reference and instant claims 11, 14, 16, 20, 21, 23 and 24 is that it does not explicitly teach PDE11 inhibitor BC11-38 (without a GUCY2C agonist) as the elected species of agent to be administered; stage 1 Parkinson's disease as the elected species of individual; the limitation of PDE11 inhibitor recited in instant claims 11 and 21; and the limitations of instant claims 14, 16, 20, 23 and 24.
However, Ceyhan et al, throughout the literature, teach that similar to PDE1 and/or PDE2 taught in Hendrick et al, PDE11 hydrolyzes both cAMP and cGMP, and is expressed in brain; and specific/selective PDE11 inhibitor as a powerful tool to develop therapeutics for diseases related to cyclic nucleotide signaling defects, for example, page 155, the 2nd paragraph in Section “Introduction”; and the paragraph bridging pages 160 and 161. Ceyhan et al further teach BC11-15, BC11-19, BC11-28, BC11-38, BC11-38-1, BC11-38-2, BC11-38-3 and BC11-38-4 as specific/selective PDE11 inhibitors; wherein BC11-15, BC11-19, BC11-28, BC11-38 or BC11-38-1 has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs (human PDEs1-10), for example, page 158, Figure 4; and page 160, Figure 6. Therefore, in view of the combined teachings of Hendrick et al and Ceyhan et al, it would have been obvious to one of ordinary skilled in the art to develop a method of treating an individual in need thereof that has Parkinson’s disease characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra, wherein the method comprises administering a specific/selective PDE11 inhibitor to the individual, wherein the specific/selective PDE11 inhibitor is selected from the group consisting of BC11-15, BC11-19, BC11-28, BC11-38, BC11-38-1, BC11-38-2, BC11-38-3 and BC11-38-4; and wherein the specific/selective PDE11 inhibitor BC11-15, BC11-19, BC11-28, BC11-38 or BC11-38-1 has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs (human PDEs1-10). It reads on PDE11 inhibitor BC11-38 as the elected species of agent to be administered.
With regards to the limitations recited in instant claims 20, 23 and 24, in the instant case, since the specific/selective PDE11 inhibitor in the method developed from the combined teachings of Hendrick et al and Ceyhan et al above meets all the limitations of the selective PDE11 inhibitor recited in instant claims 11 and 21, the specific/selective PDE11 inhibitor in the method developed from the combined teachings of Hendrick et al and Ceyhan et al above would necessarily have the same properties and functionality of the selective PDE11 inhibitor recited in instant claims 11 and 21. Therefore, the specific/selective PDE11 inhibitor in the method developed from the combined teachings of Hendrick et al and Ceyhan et al above would have the property of increasing phosphorylation of serine 40 of tyrosine hydroxylase (TH) in a dopaminergic cell, and alleviating motor abnormalities of the individual. Furthermore, the MPEP states “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).” (see MPEP § 2112.01 I). In addition, since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
Furthermore, Stocchi et al teach that Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is manifested clinically by a resting tremor, rigidity and bradykinesia; and the early period after diagnosis is critical in terms of rate of progression, but it is also in the early stage of the disease that an intervention able to modify the natural course of the disease may be more successful, for example, page 1, the 1st and 2nd paragraphs in Section “When to start treatment”.
In addition, the Stages of Parkinson’s Disease document teaches there are 5 stages of PD, with stage 1 being the earliest state, for example, page 1.
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Hendrick et al, Ceyhan et al, Stocchi et al and the Stages of Parkinson’s Disease document to develop a method of treating an individual in need thereof that has Parkinson’s disease characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra, wherein the method comprises administering a specific/selective PDE11 inhibitor to the individual; wherein specific/selective PDE11 inhibitor is selected from the group consisting of BC11-15, BC11-19, BC11-28, BC11-38, BC11-38-1, BC11-38-2, BC11-38-3 and BC11-38-4; wherein the specific/selective PDE11 inhibitor BC11-15, BC11-19, BC11-28, BC11-38 or BC11-38-1 has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs (human PDEs1-10); wherein the specific/selective PDE11 inhibitor increases phosphorylation of serine 40 of tyrosine hydroxy lase (Th) in a dopaminergic cell and alleviates motor abnormalities of the individual; and wherein the individual has stage 1 Parkinson’s disease. It reads on stage 1 Parkinson's disease as the elected species of individual.
One of ordinary skilled in the art would have been motivated to combine the teachings of Hendrick et al, Ceyhan et al, Stocchi et al and the Stages of Parkinson’s Disease document to develop a method of treating an individual in need thereof that has Parkinson’s disease characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra, wherein the method comprises administering a specific/selective PDE11 inhibitor to the individual; wherein specific/selective PDE11 inhibitor is selected from the group consisting of BC11-15, BC11-19, BC11-28, BC11-38, BC11-38-1, BC11-38-2, BC11-38-3 and BC11-38-4; wherein the specific/selective PDE11 inhibitor BC11-15, BC11-19, BC11-28, BC11-38 or BC11-38-1 has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs (human PDEs1-10); wherein the specific/selective PDE11 inhibitor increases phosphorylation of serine 40 of tyrosine hydroxy lase (Th) in a dopaminergic cell and alleviates motor abnormalities of the individual; and wherein the individual has stage 1 Parkinson’s disease, because Ceyhan et al, throughout the literature, teach that similar to PDE1 and/or PDE2 taught in Hendrick et al, PDE11 hydrolyzes both cAMP and cGMP, and is expressed in brain; and specific PDE11 inhibitor as a powerful tool to develop therapeutics for diseases related to cyclic nucleotide signaling defects. Ceyhan et al further teach BC11-15, BC11-19, BC11-28, BC11-38, BC11-38-1, BC11-38-2, BC11-38-3 and BC11-38-4 as specific/selective PDE11 inhibitors; wherein BC11-15, BC11-19, BC11-28, BC11-38 or BC11-38-1 has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs (human PDEs1-10). Therefore, in view of the combined teachings of Hendrick et al and Ceyhan et al, it would have been obvious to one of ordinary skilled in the art to develop a method of treating an individual in need thereof that has Parkinson’s disease characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra, wherein the method comprises administering a specific/selective PDE11 inhibitor to the individual, wherein the specific/selective PDE11 inhibitor is selected from the group consisting of BC11-15, BC11-19, BC11-28, BC11-38, BC11-38-1, BC11-38-2, BC11-38-3 and BC11-38-4; and wherein the specific/selective PDE11 inhibitor BC11-15, BC11-19, BC11-28, BC11-38 or BC11-38-1 has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs (human PDEs1-10). Stocchi et al teach that Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is manifested clinically by a resting tremor, rigidity and bradykinesia; and the early period after diagnosis is critical in terms of rate of progression, but it is also in the early stage of the disease that an intervention able to modify the natural course of the disease may be more successful. And the Stages of Parkinson’s Disease document teaches there are 5 stages of PD, with stage 1 being the earliest state.
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Hendrick et al, Ceyhan et al, Stocchi et al and the Stages of Parkinson’s Disease document to develop a method of treating an individual in need thereof that has Parkinson’s disease characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra, wherein the method comprises administering a specific/selective PDE11 inhibitor to the individual; wherein specific/selective PDE11 inhibitor is selected from the group consisting of BC11-15, BC11-19, BC11-28, BC11-38, BC11-38-1, BC11-38-2, BC11-38-3 and BC11-38-4; wherein the specific/selective PDE11 inhibitor BC11-15, BC11-19, BC11-28, BC11-38 or BC11-38-1 has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs (human PDEs1-10); wherein the specific/selective PDE11 inhibitor increases phosphorylation of serine 40 of tyrosine hydroxy lase (Th) in a dopaminergic cell and alleviates motor abnormalities of the individual; and wherein the individual has stage 1 Parkinson’s disease.
Response to Applicant's Arguments
16. Applicant argues that: 1) The amended claims are distinguishable from the primary reference Hendrick; and 2) The secondary references Ceyhan, Stocchi, and Stages of Parkinson's Disease fail to cure the deficiencies of Hendrick.
17. Applicant's arguments have been fully considered but have not been found persuasive.
Please note: As stated in Section 12 above, in the instant case, the Examiner is interpretating treating the instant claimed individual with either a selective PDE11 inhibitor or a combination of a selective PDE11 inhibitor and a PDE2 inhibitor would inherently result in a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10% recited in instant claims 11 and 21. Therefore, any arguments related to such limitation are moot.
Furthermore, the Examiner would like to point out that instant claims 11, 14, 16, 20, 21, 23 and 24 are rejected under 35 U.S.C. 103 (obviousness type), and the rejection is based on the combined teachings of Hendrick et al, Ceyhan et al, Stocchi et al and the Stages of Parkinson’s Disease document; therefore, it is not necessary for each of the cited references to teach all the limitations of instant claims. In addition, the Examiner would like to point out that the MPEP states "One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references…" (see MPEP § 2145 IV).
In response to Applicant’s arguments that 1) The amended claims are distinguishable from the primary reference Hendrick:
First, as stated above, the rejection is based on the combined teachings of Hendrick et al, Ceyhan et al, Stocchi et al and the Stages of Parkinson’s Disease document; therefore, it is not necessary for Hendrick et al to teach all the limitations of instant claims.
Second, in the instant case, as stated in Section 15 above, Hendrick et al, throughout the patent, explicitly teach both PDE1 and PDE2 are PDE that hydrolyzes both cAMP and cGMP; a product comprising a PDE1 inhibitor and a PDE2 inhibitor, in free or salt form; pharmaceutical compositions comprising such product; and a method of treating an individual has cAMP and/or cGMP related disorders, wherein the method comprises administering such product to said individual, and wherein the cAMP and/or cGMP related disorder can be Parkinson's disease. Therefore, Hendrick et al explicilty provide scientific connection between inhibiting the hydrolysis of both cAMP and cGMP and treating PD. And the Examiner has shown that inhibiting the degradation of cAMP and cGMP for treating Parkinson’s disease is known in the art; and the Examiner’s previous statement of “Parkinson's disease is a cAMP and/or cGMP related disorder that can be treated with an agent that inhibits the hydrolysis of both cAMP and cGMP” is fully supported by Hendrick et al. Furthermore, the Examiner would like to point out that as stated in MPEP: “I. PRIOR ART IS PRESUMED TO BE OPERABLE/ENABLING” (see MPEP § 2121 I). And in the instant case, other than statements/arguments, Applicant fails to provide any evidence and/or data to indicate the method taught in Hendrick et al is not enabled.
Third, the Examiner understands Applicant has provided few articles about either Parkinson's disease (PD) or PDEs, in particular PDE11. However, in the instant case, with regards to the cited and filed Poewe et al (2017) reference, it appears to the Examiner that Applicant assumes such reference is a comprehensive review of Parkinson's disease that includes all information about PD pathogenesis and treatment. However, in view of the teachings of Hendrick et al, it is clear that the cited and filed Poewe et al (2017) reference fails to includes all information about PD pathogenesis and treatment. Therefore, it is unclear to the Examiner on what Applicant’s assumption is based. Further clarification is required. With regards to the cited and filed Heckman et al (2016) and Lakies et al (2010) references, the Examiner would like to point out the instant rejection is not based on the effect of PDE11 inhibitor on dopaminergic system. Therefore, it is unclear to the Examiner how and/or why the cited and filed Heckman et al (2016) is relevant to instant rejection. Further clarification is required. Furthermore, the Examiner understand that Lakies et al do not show either the protein level or its enzymatic activity of PDE11 in brain. However, in the instant case, other than statements/arguments, Applicant fails to present any data and/or evidence to show PDE11 protein is not expressed in brain or the expressed PDE11 is inactive. In addition, as stated in Section 15 above, Ceyhan et al, throughout the literature, explicilty teach that similar to PDE1 and/or PDE2 taught in Hendrick et al, PDE11 hydrolyzes both cAMP and cGMP, and is expressed in brain; and specific PDE11 inhibitor as a powerful tool to develop therapeutics for diseases related to cyclic nucleotide signaling defects. With regards to the cited and filed Kelly et al (2010) reference, it appears to the Examiner that Applicant assumes such reference is a comprehensive article of PDE11 that includes all information about PDE11. However, the Examiner would like to point out that the cited and filed Kelly et al (2010) reference is a publication of research data related to one specific property and/or functionality of PDE11. Therefore, one of ordinary skilled in the art would understand and reasonably expect the cited and filed Kelly et al (2010) reference does not include every single property and/or functionality of PDE11. Thus, it is unclear to the Examiner on what Applicant’s assumption is based. Further clarification is required.
In response to Applicant’s arguments that 2) The secondary references Ceyhan, Stocchi, and Stages of Parkinson's Disease fail to cure the deficiencies of Hendrick:
First, as stated above, the rejection is based on the combined teachings of Hendrick et al, Ceyhan et al, Stocchi et al and the Stages of Parkinson’s Disease document; therefore, it is not necessary for Ceyhan et al to teach the scientific connection between inhibiting the hydrolysis of both cAMP and cGMP and treating PD, since such scientific connection is explicitly taught in Hendrick et al.
Second, as stated in both the previous office action and Section 15 above, in the instant case, Hendrick et al, throughout the patent, explicitly teach both PDE1 and PDE2 are PDE that hydrolyzes both cAMP and cGMP; a product comprising a PDE1 inhibitor and a PDE2 inhibitor, in free or salt form; pharmaceutical compositions comprising such product; and a method of treating an individual has cAMP and/or cGMP related disorders, wherein the method comprises administering such product to said individual, and wherein the cAMP and/or cGMP related disorder can be Parkinson's disease. Therefore, in view of the teachings of Hendrick et al as a whole, one of ordinary skilled in the art would understand that Parkinson's disease is a cAMP and/or cGMP related disorder that can be treated with an agent that inhibits the hydrolysis of both cAMP and cGMP. Furthermore, Ceyhan et al, throughout the literature, teach that similar to PDE1 and/or PDE2 taught in Hendrick et al, PDE11 hydrolyzes both cAMP and cGMP, and is expressed in brain; and specific PDE11 inhibitor as a powerful tool to develop therapeutics for diseases related to cyclic nucleotide signaling defects. Therefore, in view of the combined teachings of Hendrick et al and Ceyhan et al as set forth in Section 15 above, it would have been obvious to one of ordinary skilled in the art, and/or one of ordinary skilled in the art would have been motivated to develop a method of treating an individual in need thereof that has Parkinson’s disease characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra, wherein the method comprises administering a specific/selective PDE11 inhibitor to the individual, wherein the specific/selective PDE11 inhibitor is selected from the group consisting of BC11-15, BC11-19, BC11-28, BC11-38, BC11-38-1, BC11-38-2, BC11-38-3 and BC11-38-4; and wherein the specific/selective PDE11 inhibitor BC11-15, BC11-19, BC11-28, BC11-38 or BC11-38-1 has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs (human PDEs1-10).
Third, with regards to Applicant’s arguments about hindsight reasoning, in the instant case, Applicant fails to point to any facet of instant rejection that is not found in the cited prior art references. It is unclear to the Examiner which part of the instant rejection is not based on the combined teachings of the cited prior art references. Merely pointing out the differences between each of the cited references and instant claimed invention is not proof of hindsight reasoning. Furthermore, the MPEP states “"[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper." In re McLaughlin, 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971).” (see MPEP § 2145).
Fourth, with regards to Applicant’s arguments about reasonable expectation of success, the Examiner would like to point out that the conclusion paragraph at the end of the rejection is based on the combined teachings of the cited prior art references set forth before such conclusion paragraph. It is unclear to the Examiner how and/or why such conclusion is baseless, and what kind of base Applicant is expected. Further clarification is required. Furthermore, the Examiner would like to point out that other than pure toxicity that kills every cells, there is no known drug and/or therapeutics that targets every single pathway involved in a disease, including PD. As an example, the treatment disclosed in the cited and filed Poewe et al (2017) reference does not target every single pathway associated with PD. Therefore, it is unclear to the Examiner why and/or how identifying and targeting the cAMP and cGMP pathway would not be able to treat PD; and in view of the teachings of Hendrick et al, how and/or why Applicant firmly believes targeting the cAMP and cGMP pathway would not be able to treat PD. Further clarification is required. Therefore, in the instant case, in view of the combined teachings of the cited prior art references as set forth in Section 15 above, a person of ordinary skilled in the art would have reasonable expectation of success in developing the methods recited in instant claims 11, 14, 16, 20, 21, 23 and 24. And, with regards to the expectation of success, the MPEP states: “Absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, a degree of predictability that one of ordinary skill would have found to be reasonable is sufficient. The Federal Circuit concluded that “[g]ood science and useful contributions do not necessarily result in patentability.” Id. at 1364, 83 USPQ2d at 1304.” (see MPEP § 2145).
Furthermore, it appears to the Examiner that Applicant has identified latent property of PDE11 inhibitor in treating PD. The Examiner would like to point out that as stated in MPEP: “Prima Facie Obviousness Is Not Rebutted by Merely Recognizing Additional Advantages or Latent Properties Present But Not Recognized in the Prior Art” (see MPEP § 2145 II).
In addition, the Examiner would like to point out that the rejection set forth in Section 15 above is not based on “obvious to try”. Therefore, Applicant’s arguments related to “obvious to try” are moot.
Taken all these together, the rejection is deemed proper and is hereby maintained.
Obviousness Double Patenting
18. 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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
19. (Revised due to Applicant’s amendment to the claim) Claims 11, 14, 16, 20, 21, 23 and 24 remain/are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-3 of co-pending Application No. 16/490192, and as evidenced by Kalia et al (Lancet, 2015, 386, pages 896-912), and in view of Hendrick et al (WO 2015/106032 A1, filed with IDS) and Ceyhan et al (Chemistry & Biology, 2012, 19, pages 155-163, filed with IDS).
20. Instant claims 11, 14, 16, 20, 21, 23 and 24 are drawn to a method of treating an individual in need thereof that has Parkinson’s disease characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra, the method comprising administering a selective phosphodiesterase (PDE) 11 inhibitor or a combination of a selective PDE11 inhibitor and a PDE2 inhibitor to the individual, in a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10%; and/or administering a phosphodiesterase (PDE) 11 inhibitor or a combination of a PDE11 and a PDE2 inhibitor to the individual, in a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10%, wherein the PDE11 inhibitor has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs.
Please note: As stated in Section 12 above, in the instant case, the Examiner is interpretating treating the instant claimed individual with either a selective PDE11 inhibitor or a combination of a selective PDE11 inhibitor and a PDE2 inhibitor would inherently result in a manner that stimulates an increase of dopamine production in a dopaminergic cell in the substantia nigra of at least 10% recited in instant claims 11 and 21.
21. Claims 1-3 of co-pending Application No. 16/490192 are drawn to a method of treating tremor and other movement symptoms in an individual that has Parkinson's disease comprising activating Guanylate Cyclase 2C (GUCY2C) signaling by administering a Guanylate Cyclase 2C (GUCY2C) agonist as a sole active pharmaceutical ingredient to the brain of the individual in need thereof to increase dopamine production and ameliorate tremor and other movement symptoms, wherein said agonist is without an additional therapeutic moiety or an additional diagnostic moiety conjugated to it.
In the instant case, in view of the combined teachings of claims 1-3 of co-pending Application No. 16/490192, it would have been obvious to one of ordinary skilled in the art to develop a method of treating tremor and other movement symptoms in an individual that has Parkinson's disease comprising administering a combination of PDE inhibitor and a Guanylate Cyclase 2C (GUCY2C) agonist as an active pharmaceutical ingredient to the brain of the individual in need thereof, wherein said agonist is without an additional therapeutic moiety or an additional diagnostic moiety conjugated to it, and wherein the individual has Parkinson's disease stage 1, 2, 3 or 4. And as evidenced by Kalia et al, Parkinson’s disease is characterized by a decrease in dopamine production resulting from degeneration of dopaminergic neurons in the substantia nigra (see for example, Abstract; and page 896, Section “Introduction”).
22. The difference between the method developed from the combined teachings of claims 1-3 of co-pending Application No. 16/490192 above and the method recited in instant claims 11, 14, 16, 20, 21, 23 and 24 is the method developed from the combined teachings of claims 1-3 of co-pending Application No. 16/490192 above does not explicitly teach the PDE11 inhibitor recited in instant claims 11, 16 and 21; and the limitation of instant claim 20.
However, Hendrick et al, throughout the patent, teach both PDE1 and PDE2 are PDE that hydrolyzes both cAMP and cGMP; a product comprising a PDE1 inhibitor and a PDE2 inhibitor, in free or salt form; pharmaceutical compositions comprising such product; and a method of treating an individual has cAMP and/or cGMP related disorders, wherein the method comprises administering such product to said individual, and wherein the cAMP and/or cGMP related disorder can be Parkinson's disease, for example, Abstract; page 1, paragraphs [0002] and [0003]; page 3, paragraph [0007]; pages 5-6, paragraph [0014]; page 13, paragraphs [0032] and [0033]; and claims 10, 11, 14 and 15.
Furthermore, Ceyhan et al, throughout the literature, teach that similar to PDE1 and/or PDE2 taught in Hendrick et al, PDE11 hydrolyzes both cAMP and cGMP, and is expressed in brain; and specific PDE11 inhibitor as a powerful tool to develop therapeutics for diseases related to cyclic nucleotide signaling defects, for example, page 155, the 2nd paragraph in Section “Introduction”; and the paragraph bridging pages 160 and 161. Ceyhan et al further teach BC11-15, BC11-19, BC11-28, BC11-38, BC11-38-1, BC11-38-2, BC11-38-3 and BC11-38-4 as specific/selective PDE11 inhibitors; wherein BC11-15, BC11-19, BC11-28, BC11-38 or BC11-38-1 has an IC50 for PDE11 that is at least 10 times lower than the IC50 for all other human PDEs (human PDEs1-10), for example, page 158, Figure 4; and page 160, Figure 6.
Therefore, in view of the combined teachings of Hendrick et al and Ceyhan et al, it would have been obvious to one of ordinary skilled in the art to modify the method developed from the combined teachings of claims 1-3 of co-pending Application No. 16/490192 and develop the method recited in instant claims 11, 14, 16, 21, 23 and 24.
With regards to the limitation recited in instant claim 20, in the instant case, since the specific/selective PDE11 inhibitor in the method developed above meets all the limitations of the selective PDE11 inhibitor recited in instant claim 11, the specific/selective PDE11 inhibitor in the method developed above would necessarily have the same properties and functionality of the selective PDE11 inhibitor recited in instant claim 11. Therefore, the specific/selective PDE11 inhibitor in the method developed above would have the property of increasing phosphorylation of serine 40 of tyrosine hydroxylase (TH) in a dopaminergic cell. Furthermore, the MPEP states “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).” (see MPEP § 2112.01 I). In addition, since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Response to Applicant's Arguments
23. Applicant argues that “As explained above, the amended claims are distinguishable from claims 1-3 of the co- pending Application No. 16/490,192 in view of Hendrick et al. and Ceyhan et al.”
24. Applicant's arguments have been fully considered but have not been found persuasive.
Applicant’s arguments about “the amended claims are distinguishable from claims 1-3 of the co- pending Application No. 16/490,192 in view of Hendrick et al. and Ceyhan et al” have been addressed in Section 17 above.
Therefore, until a proper terminal disclaimer is filed and approved by the Office, the double patenting rejection is maintained.
Conclusion
No claim is allowed.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658