DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Elections/ Restrictions
Applicant's election of (1) the species of the formula of claim 102, and (2) the species of a biguanide (specifically metformin) in the reply filed on April 10 is acknowledged with appreciation. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
3. Claims 92-107 are readable on the elected species. The non-elected subject matter is presently withdrawn from consideration, i.e., claims 94, 97 and 98, drawn to non-elected compounds, are presently withdrawn from consideration.
4. Claims 92, 93, 95, 96 and 99-107 are under examination with the elected species and are the subject of this office action.
Information Disclosure Statement
5. Applicant’s information disclosure statements (IDS) submitted June 28, 2024 (two statements), July 1, 2024 December 30, 2024, July 8, 2025, and May 13, 2026, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner, please refer to the signed copies of Applicant’s PTO-1449 forms, attached herewith.
Claim Rejections - 35 USC § 112(a)
6. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
7. Claims 92-107 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a Db/Db mouse in need thereof comprising administering to the mouse in need thereof an effective amount of a composition comprising: (a) compound 102, does not reasonably provide enablement for a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human in need thereof comprising administering to the human in need thereof an effective amount of a composition comprising the combination of (a) a compound of the formula of claim 92, claim 99, or claim 102, AND (b) any statin, any biguanide, any PPAR agonist, any anti-obesity drug, any hormone, any insulin secretagog, any sulfonylurea-based drug, or any a-glucosidase inhibitor, as instantly recited.
8. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The standard for determining whether the Specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), that is still the standard to be applied, determined by consideration of the Wands factors (MPEP 2164.01(A)); namely, nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered, with the most relevant factors discussed below.
9. Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
In the instant case, the claimed invention pertains to a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human in need thereof comprising administering to the human in need thereof an effective amount of a composition comprising (a) a compound of the formula of claim 92, claim 99, or claim 102, AND (b) any statin, any biguanide, any PPAR agonist, any anti-obesity drug, any hormone, any insulin secretagog, any sulfonylurea-based drug, or any a-glucosidase inhibitor, as instantly recited.
10. The State of the Prior Art and the Relative Skill of those in the Art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.”
As discussed above, the instantly claimed invention pertains to a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human in need thereof comprising administering to the human in need thereof an effective amount of a composition comprising (a) a compound of the formula of claim 92, claim 99, or claim 102, AND (b) any statin, any biguanide, any PPAR agonist, any anti-obesity drug, any hormone, any insulin secretagog, any sulfonylurea-based drug, or any a-glucosidase inhibitor, as instantly recited.
11. At the time the instant application was filed, it would have been known by those of ordinary skill in the art that component (b) of the claims embraces a vast scope of additional drugs/agents:the class of statins includes, but are not limited to, atorvastatin, pravastatin, fluvastatin, lovastatin, simvastatin, and cerivastatin. PPAR agonists as a class include thiazolidinediones or fibrates; wherein thiazolidinediones include 5-((4-(2-(methyl-2-pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazolidinedione, troglitazone, pioglitazone, ciglitazone, WAY-120,744, englitazone, AD 5075, darglitazone, and rosiglitazone. The class of anti-obesity drugs includes β-adrenergic receptor agonists, such as β-3 receptor agonists, sibutramine, bupropion, fluoxetine, and phentermine. Hormones as a class include thyroid hormone, estrogen and insulin wherein insulins include injectable insulin, transdermal insulin, inhaled insulin, or any combination thereof. Insulin secretagogues include forskolin, dibutryl cAMP or isobutylmethyl-xanthine (IBMX). Sulfonylurea-based drugs as a class include glisoxepid, glyburide, acetohexamide, chlorpropamide, glibornuride, tolbutamide, tolazamide, glipizide, gliclazide, gliquidone, glyhexamide, phenbutamide, and tolcyclamide. Biguanides include metformin, phenformin and buformin. The class of α-glucosidase inhibitors includes acarbose and miglitol.
The level of skill to practice the art of the instantly claimed invention is high and requires a variety of skills usually found in institutions and companies that employ highly trained and skilled scientists to carry out these tasks.
12. The Level of Predictability in the Art: Despite the advanced training of those in the art, the pharmaceutical art is highly unpredictable. It is still not possible to predict the pharmacological activity or treatment efficacy of a compound based on the structure alone. Typically, in order to verify that a compound will be effective in a method or treating a disease, the compounds must be either tested directly in a patient or in a model that has been established as being predictive of efficacy. It is not predictable from the specification or from the prior art that each of the drugs/agents recited in component (b) of the claims effectively treats pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human subject in need thereof or in a culture, i.e., in vitro.
13. The level of detail required to satisfy the enablement requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172; Capon v. Eshhar, 418 F.3d 1349, 1357-58, 76 USPQ2d 1078, 1083-84 (Fed. Cir. 2005). The fields of biology and chemistry are considered “unpredictable” because the complexity and unpredictability of chemical and biological interactions can make it difficult to understand the exact properties of an invention. A person of ordinary skill in the art from the specification or from the prior art cannot predict the pharmacological effects of administration of the instant formulation in subjects in regards to prevention of pain. The pharmaceutical industry is the prototypical example of a highly unpredictable field. Pfizer v. Teva Pharm., 482 F.Supp.2d 390, 413 (D.N.J. 2007); 2 Chisum on Patents § 5.04.
14. The Amount of Direction Provided by the Inventor / Existence of Working Examples: The amount of direction provided by the Applicant is considered to be determined by the Specification and the working examples. In the instant case, the Specification discloses only the in vitro activity and in vivo efficacy of administering compound 102 to Db/Db mice for preventing pancreatic beta cell degeneration (Examples 1-7). The Specification does not disclose any working examples of component (b), let alone the effects of the combined administration of (a) a compound of the formulae of claims 92, 99, or 101 together with component (b), as recited by the claims.
15. Scope or Breadth of the Claims: As stated in MPEP 2164.01(c), “[w]hen a compound or composition claim is limited by a particular use, enablement of that claim should be evaluated based on that limitation.” Thus, as stated in MPEP 2164.08, “[t]he focus of the examination inquiry is whether everything within the scope of the claim is enabled” (emphasis added). Indeed, the Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright, 999 F.2d 1557 (Fed. Cir. 1993) (emphasis added).
16. At the same time, however, it is also recognized that not everything necessary to practice the invention need be disclosed. Nor is it necessary that an Applicant test all the embodiments of his invention. In re Angstadt, 537 F.2d 498 (CCPA 1976) (emphasis added). In fact, as stated by the court in In re Buchner, 929 F.2d 660 (Fed. Cir. 1991), a patent need not teach, and preferably omits, what is well known in the art.
17. Accordingly, for purposes of enablement, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate in scope with the protection sought by the claims. Thus, while “a patent application is entitled to claim his invention generically” it is necessary that “he provide a disclosure sufficient to enable one skilled in the art to carry out the invention commensurate with the scope of his claims". Amgen, Inc, v. Chugai Pharmaceutical Co., Ltd. (Fed. Cir. 1991). As noted by the court in In re Fisher, 427 F.2d 833 (CCPA 1970), the scope of enablement must bear a “reasonable correlation” to the scope of the claims. See also Ak Steel Corp. v. Sollac, 344 F.3d 1234 (Fed. Cir. 2003) and In re Moore, 439 F.2d 1232 (CCPA 1971). As stated in MPEP 2164.08, resolution of this concern requires two stages of inquiry: “[t]he first is to determine how broad the claim is with respect to the disclosure. The entire claim must be considered. The second inquiry is to determine if one skilled in the art is enabled to make and use the entire scope of the claim without undue experimentation”.
18. As to the first inquiry, as discussed above, the claims are drawn to a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human in need thereof comprising administering to the human in need thereof an effective amount of a composition comprising (a) a compound of the formula of claim 92, claim 99, or claim 102, AND (b) any statin, any biguanide, any PPAR agonist, any anti-obesity drug, any hormone, any insulin secretagog, any sulfonylurea-based drug, or any a-glucosidase inhibitor, as instantly recited. Considering that component (b) of the claims encompasses hundreds of millions of compounds/drugs/agents, and potentially billions, it is evident that the claims are broad (please refer to paragraph “11” above regarding the scope of any statin, any biguanide, any PPAR agonist, any anti-obesity drug, any hormone, any insulin secretagog, any sulfonylurea-based drug, or any a-glucosidase inhibitor embraced by the claims). Yet, as discussed above, the instant Specification discloses the treatment of pancreatic beta cell degeneration comprising administering (a) only one compound, i.e. compound 102, and fails to disclose the administration of any drug or agent of component (b) as recited by the claims. As such, the claim is extremely broad with respect to the disclosure. The second inquiry is discussed in detail below.
19. Amount of Experimentation Necessary: In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the invention as claimed. As discussed above, the claims are drawn to a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human in need thereof comprising administering to the human in need thereof an effective amount of a composition comprising (a) a compound of the formula of claim 92, claim 99, or claim 102, AND (b) any statin, any biguanide, any PPAR agonist, any anti-obesity drug, any hormone, any insulin secretagog, any sulfonylurea-based drug, or any a-glucosidase inhibitor, or combinations thereof. Since identifying any compound or drug which is capable of modulating the activity of a specific receptor, ion channel, or enzyme is extremely complex, the nature of the instant invention considered to be one of extreme complexity. In the instant case, this complexity is exacerbated by the broadness of the combined administration of compound (a) and component (b) with respect to the disclosure since component (b) encompasses hundreds of millions of compounds/drugs/agents and potentially billions of compounds/ drugs/agents, whereas the instant Specification discloses only the administration of compound 102 and does not disclose the administration of any compounds embraced by component (b) and exerting the disclosed activity. Although the relative skill of those in the art to which the invention pertains is high, the state of the art and unpredictability within the art is such that even the most talented artisan could not reasonably predict which of the hundreds of millions of compounds/drugs/agents encompassed by component (b) in combination with compound (a) would exert the alleged activity based on the lack of disclosure.
20. Given the unpredictability of the art, the only way to ascertain which of the hundreds of millions, and potentially billions, of claimed compounds/drugs/ agents encompassed by component (b) are usable in composition combined with compound (a), based on the limited disclosure, would require undue experimentation. That is, the only way one skilled in the art is enabled to use the entire scope of the claim based on the instant disclosure entails undue experimentation.
To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure.
Claim Rejections - 35 USC § 103
20. The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
21. The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
22. This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
23. Claims 92, 93, 95, 96, and 99-107 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Reaume et al., U.S. 20070093516 A1, as evidenced by Hong et al., Biomol. Ther. (2013), and in view of Butler et al. Diabetes (2003).
Claim 92 recites a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human in need thereof, comprising administering to the mammal in need thereof an effective amount of a composition comprising:
(a) a compound of formula:
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(claims 93, 95 and 96), and
(b) a statin, a biguanide, a PPAR agonist, an anti-obesity drug, a hormone, an insulin secretagog, a sulfonylurea-based drug, or an a-glucosidase inhibitor, (more specifically, the biguanide metformin).
Claim 99 recites a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human in need thereof, comprising administering to the mammal in need thereof an effective amount of a composition comprising:
(a) a compound of formula:
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(claims 100 and 101), and
(b) a statin, a biguanide, a PPAR agonist, an anti-obesity drug, a hormone, an insulin secretagog, a sulfonylurea-based drug, or an a-glucosidase inhibitor, (more specifically, the biguanide metformin).
Claim 102 is drawn to a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human in need thereof, comprising administering to the mammal in need thereof an effective amount of an oral composition comprising:
(a) 0.5 mg to 20 mg per kg body weight of a compound of formula:
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, and
(b) a statin, a biguanide, a PPAR agonist, an anti-obesity drug, a hormone, an insulin secretagog, a sulfonylurea-based drug, or an a-glucosidase inhibitor, (more specifically, the biguanide metformin (claims 105-107)), and
wherein the oral composition is a solution, suspension, emulsion, tablet, pill, capsule, or sustained-release formulation (claim 104).
24. Reaume et al. disclose a method of treating Type II diabetes comprising administering a composition comprising “Compound 102” to Db/Db mice of at least 8 weeks of age (page 15, left column, “6.4 Example 4 In vivo Db/Db Mouse Study,” in particular paragraph [0179]). Compound 102 is a position isomer of Applicant’s instant compound of claim 102 and of claims 92 and 99 wherein “R1” is methyl in a meta position, “n” is 1, and “m” is 0:
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(Reume et al., page 6, left column). Reaume et al. additionally disclose a compound of formula (V):
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, which is the same compound that is instantly recited in claim 102, also known as Tolimidone, “NSC 314335” or “MLR-1023” (page 2, paragraphs [0018]). And, one skilled in the art at the time of filing would know that compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09. As such, one skilled in the art at the time of filing would have been motivated substitute the compound of Formula (V) for Compound 102 of Reume et al., for administration to the Db/Db mice in Example 4, with the expectation that compounds similar in structure will have similar properties.
25. Reume et al. teach oral administration at specific doses of 5 mg/kg and 15 mg/kg (see 6.4 Example 4, paragraph [0179]), and teach a preferred embodiment of oral dosage of 0.5 mg/kg to 20 mg/kg:
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(please see page 12, paragraph [0136], middle of paragraph), which fully embraces the dosage range required by instant claim 102. Reume et al. teach that the invention provides method of treatment by administration to a patient, wherein the patient is preferably a human. (See paragraph [0125]).
26. Reume et al. go on to suggest the combined administration with a biguanide, and specifically name metformin in a small subgenus of just three compounds:
“The present compositions can also be administered together with a biguanide. Biguanides for use in combination with the compounds of the invention include but are not limited to metformin, phenformin and buformin,” [emphasis added], (paragraph [0151]). Therefore, one skilled in the art would have been motivated at the time of filing to combine a compound of formula (V) and metformin into a composition for treating Type II diabetes, with a reasonable expectation of success. And, the rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law, please see In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings). Furthermore, MPEP 2144 teaches that the strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In the instant case, two known compounds which individually demonstrate efficacy for treating Type II diabetes could be combined in a composition in order to achieve an additive effect in a patient in need thereof, with a reasonable expectation of success.
Please refer to MPEP 2144.06 “I. COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE” wherein Kerkhoven is specifically referenced:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
27. Regarding the limitation in the preamble of treating pancreatic beta cell degeneration, it is clear as evidenced by Hong et al., that Db/Db mice are characterized by degeneration of pancreatic islets and islet beta cells, i.e.:
“db/db mice (C57BLKS db/db) lack a functional leptin receptor by homozygous mutation of leptin receptor gene. They spontaneously develop obesity, hyperinsulinemia, and glucose intolerance at 4-6 week of age, progressing to diabetes by about 10 weeks of age (Leiter, 1989). The decrease in plasma insulin level and increase in blood glucose level are correlated to a degeneration of the pancreatic islets and destruction of the islet beta cells. They have thus been used extensively as a model for Type II diabetes,” [emphasis added] (page 288, right column, under “Discussion”).
(It is noted that the Hong et al. reference is relied upon as an evidentiary reference, i.e., Hong et al. identifies the characteristics of Db/Db mice, i.e., that Db/Db mice are characterized by degeneration of pancreatic islets and islet beta cells. As such, the Hong et al. publication date does not to be available as prior art before Applicant’s filing date.)
28. Thus, Reume et al. teach a method of treating pancreatic beta cell degeneration in a mammalian model of Type II diabetes, wherein the mice suffer from degeneration of the pancreatic islets and destruction of the islet beta cells, i.e., a mammal in need thereof, comprising administering a compound of formula (V) in combination with the biguanide metformin to said mammal, but do not explicitly teach administration to a human.
29. However, Reume et al. specifically teach that the compound of the invention is preferably administered to a human patient (paragraph [0125]). And, Butler et al. teach that humans with Type 2 diabetes demonstrate increased beta cell death (aka b-cell apoptosis):
“the frequency of b-cell apoptosis was increased 10-fold in lean and 3-fold in obese cases of type 2 diabetes compared with their respective nondiabetic control group (P < 0.05). We conclude that b-cell mass is decreased in type 2 diabetes and that the mechanism underlying this is increased b-cell apoptosis.” (see abstract).
Butler et al. go on to suggest targeting b-cell apoptosis as a therapeutic strategy in the treatment of Type 2 diabetes in humans:
“Since the major defect leading to a decrease in b-cell mass in type 2 diabetes is increased apoptosis, while new islet formation and b-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 diabetes, because this approach might actually reverse the disease to a degree.” (see abstract).
30. As such, one skilled in the art at the time of filing would have been motivated to practice the method of Reume et al. by administering a compound of formula (V) in combination with metformin to a human with Type 2 diabetes and suffering from increased pancreatic beta cell degeneration (b-cell apoptosis), with a reasonable expectation of success.
Thus, claims 92, 93, 95, 96, 99-102 and 104-107 are prima facie obvious.
Claim 103 is drawn to claim 102, and limits wherein the oral composition comprises 10% to 95% of the compound of the formula.
31. Reume et al. additionally teach wherein, “[o]ral compositions preferably contain 10% to 95% active ingredient by weight,” (page 12, paragraph [0136], last line).
Therefore it would have been obvious to one of skill in the art at the time of filing to treat pancreatic beta cell degeneration comprising administering an oral composition comprising 10% to 95% of the compound of formula (V) in combination with metformin, to with a reasonable expectation of success.
As such, claim 103 is prima facie obvious.
Double Patenting Rejections
32. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
33. Claims 92, 93, 95, 96, and 99-107 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7, 8, 10-14 and 16-18 of U.S. Patent No. 7,776,870 B2 to Reaume et al., (corresponding to P.G. Pub U.S. 2007/0093516 A1 applied above), in view of Cnop et al., Diabetes 2005 (cited on Applicant’s IDS of June 28, 2024).
Although the conflicting claims are not identical, they are not patentably distinct from each other because Applicant’s instant claims recite the following:
Claim 92 recites a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human in need thereof, comprising administering to the mammal in need thereof an effective amount of a composition comprising:
(a) a compound of formula:
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(claims 93, 95 and 96) and
(b) a statin, a biguanide, a PPAR agonist, an anti-obesity drug, a hormone, an insulin secretagog, a sulfonylurea-based drug, or an a-glucosidase inhibitor, (more specifically, the biguanide metformin).
Claim 99 recites a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human in need thereof, comprising administering to the mammal in need thereof an effective amount of a composition comprising:
(a) a compound of formula:
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(claims 100 and 101), and
(b) a statin, a biguanide, a PPAR agonist, an anti-obesity drug, a hormone, an insulin secretagog, a sulfonylurea-based drug, or an a-glucosidase inhibitor, (more specifically, the biguanide metformin).
Claim 102 is drawn to a method of treating pancreatic beta cell degeneration by increasing insulin content and preserving islet structure in pancreatic islets in a human in need thereof, comprising administering to the mammal in need thereof an effective amount of an oral composition comprising:
(a) 0.5 mg to 20 mg per kg body weight of a compound of formula:
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and
(b) a statin, a biguanide, a PPAR agonist, an anti-obesity drug, a hormone, an insulin secretagog, a sulfonylurea-based drug, or an a-glucosidase inhibitor, (more specifically, the biguanide metformin (claims 105-107)), and
wherein the oral composition is a solution, suspension, emulsion, tablet, pill, capsule, or sustained-release formulation (claim 104). Claim 103 is drawn to claim 102, and limits wherein the oral composition comprises 10% to 95% of the compound of the formula.
34. The claims of U.S. Pat No. 7,776,870 B2 recite the following methods of treatment:
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, wherein the recited genera of compounds are the same as Applicant’s instantly claimed genera, more specifically wherein the compound recited in claim 4 is identical to the compound recited in Applicant’s instant Claim 102. Therefore the claims of U.S. Pat No. 7,776,870 B2 recite a method of reducing blood glucose levels or treating type II diabetes in a mammal comprising administering a composition comprising a compound of the same formula recited by instant claim 102 and embraced by the formula of instant claims 92 and 99 to a mammal in need thereof, but do not recite the administration of component (b), metformin.
35. Yet, U.S. Pat No. 7,776,870 B2 teaches that the recited compositions can also be administered together with a biguanide, i.e., “Biguanides for use in combination with the compounds of the invention include but are not limited to metformin, phenformin and buformin,” (paragraph 149).
36. U.S. Pat No. 7,776,870 B2 does not recite that the mammal is human. However in a preferred embodiment in the Specification, the patent defines the mammal as a human. In another preferred embodiment, the patent teaches that the effective amount is from about 0.1 mg to about 100 mg/kg, and that preferably the administration is oral (paragraph (17)).
37. See MPEP § 804 II.B.2(a), i.e. the specification of the reference patent may be relied upon to properly construe the scope of the reference claim, and “may be considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent.” See also In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970): those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application).
38. Regarding the limitation of the preamble of the instant claims of treating pancreatic beta-cell degeneration, Cnop et al. teach that pancreatic beta-cell degeneration/ beta-cell death is part of the pathogenesis of type II diabetes, and said patient would be considered in need of treating beta-cell degeneration and preserving islet structure (see abstract). Likewise, Cnop et al. teach that a patient with insulin resistance requires an increased amount of insulin to have the same effect, i.e. is necessarily in need of increasing insulin content (see abstract).
39. Therefore a patient with type II diabetes is in need of preventing beta cell degeneration and in need of increasing insulin content, such that one skilled in the art would be motivated to administer a composition comprising Applicant’s instantly claimed compound together with metformin to a type II diabetic patient, and would have a reasonable expectation of success in the treatment of pancreatic beta cell degeneration.
The recitation at the end of claims 92, 99, and 102: “thereby treating pancreatic beta cell degeneration,” does not patentably limit the claimed methods, but instead describes a result or property of the administration step and must necessarily result when the composition is administered to the patient.
As such, claims 92, 93, 95, 96, and 99-107 are prima facie obvious.
40. Claims 92, 92, 95, 96 and 99-107 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12,011,445 B2 in view of Reaume et al., P.G. Pub U.S. 2007/0093516 A1.
Applicant’s instant claims have been described in detail, above.
41. The claims of U.S. Pat No. 12,011,445 B2 recite the following method of treating pancreatic beta cell degeneration:
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wherein the recited genera of compounds are the same as Applicant’s instantly claimed genera, more specifically wherein the compound recited in claim 11 is identical to the compound recited in Applicant’s instant Claim 102. Therefore the claims of U.S. Pat No. 12,011,445 B2 recite the same methods of treatment in a mammal comprising administering a composition comprising the same compound of the same formula recited by instant claim 102 and embraced by the formulae of instant claims 92 and 99 to a mammal in need thereof, but do not recite the administration of component (b), metformin.
42. Reume et al. go on to suggest the combined administration with a biguanide, and specifically name metformin in a small subgenus of just three compounds:
“The present compositions can also be administered together with a biguanide. Biguanides for use in combination with the compounds of the invention include but are not limited to metformin, phenformin and buformin,” [emphasis added], (paragraph [0151]). Therefore, one skilled in the art would have been motivated at the time of filing to combine a compound of formula (V) and metformin into a composition for treating Type II diabetes, with a reasonable expectation of success. And, the rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law, please see In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings). Furthermore, MPEP 2144 teaches that the strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In the instant case, two known compounds which individually demonstrate efficacy for treating Type II diabetes could be combined in a composition in order to achieve an additive effect in a patient in need thereof, with a reasonable expectation of success.
Please refer to MPEP 2144.06 “I. COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE” wherein Kerkhoven is specifically referenced:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
43. U.S. Pat No. 12,011,445 B2 does not recite that the mammal is human.
44. However, Reume et al. teach that the invention provides method of treatment by administration to a patient, wherein the patient is preferably a human. (See paragraph [0125]). And, U.S. Pat. No. 12,011,445 B2 teaches that “In some embodiments, a composition of the invention comprising a compound of the invention and a pharmaceutically acceptable vehicle, is administered to a mammal, such as a human, with pancreatic beta cell degeneration and/or disorders associated with pancreatic beta cell degeneration,” (paragraph [0152]).
45. See MPEP § 804 II.B.2(a), i.e., the specification of the reference patent may be relied upon to properly construe the scope of the reference claim, and “may be considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent.” See also In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970): those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application).
46. As such, one skilled in the art would be motivated to practice the same method of treating pancreatic beta cell degeneration comprising administering the same compound recited in the claims of U.S. Pat No. 12,011,445 B2 to a human in need thereof, in combination with metformin, with a reasonable expectation of success.
Conclusion
47. In conclusion, claims 92-107 are present in the application, and claims 94, 97 and 98 are withdrawn from consideration. Claims 92, 93, 95, 96, and 99-107 are currently rejected. No claim is presently allowable.
48. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached on Monday-Friday 8:30AM-5PM EST.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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