DETAILED ACTION
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 .
Priority
Examiner acknowledges that, according to the Filing receipt received 12/16/2024, that the instant application 18/904,564 filed 10/02/2024 is a continuation of 17/182,715 filed 02/23/2021, which is a continuation of 16/608,457 filed 10/25/2019, which is a 371 of PCT/CN2018/086461 filed 05/11/2018 which claims foreign priority of Chinese application CN201710335467.5 filed 05/12/2017. A certified copy of the foreign priority document was received in application 16/608,457.
Claim Objections
Claims 132 and 155 are objected to because of the following informalities:
Claim 132: "claims 130" should read "claim 130";
Claim 155: “co-solvents” should read “co-solvent”.
Appropriate correction is required.
The amendment to the claims filed on 12/12/2024 does not comply with the requirements of 37 CFR 1.121(c) because claims 143-154 are not listed and their claim status is not indicated.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 38, 40, 119, 130, 132, and 134-135 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 38 and 40 recite the limitation “the one”. This limitation lacks antecedent basis as it is unclear whether “the one” refers to the pattern as a whole or particular peaks. Examiner suggests amending the claims to read “essentially the same as in FIG…”.
Claim 119 is directed toward a pharmaceutical composition comprising Form D of berberine ursodeoxycholate and a pharmaceutically acceptable excipient, carrier, or diluent. However, when looking to the specification to construe the scope of the claims, paragraph [0095] defines “pharmaceutically acceptable excipient, carrier, or diluent” to include solvents. The solid Form D of berberine ursodeoxycholate would not be expected to maintain its crystalline form in solution, yet the claim requires that Form D be present in the pharmaceutical composition. It is therefore unclear how a composition can both require the solid Form D and include excipients, carriers, or diluents that are solvents. Claims 130, 132, and 134-135 are rejected for requiring the limitation at issue.
Regarding claim 135, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 135, the phrase "including" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention or if other alternatives are encompassed by the claim. See MPEP § 2173.05(d) and 2173.05(h).
Regarding claim 135, the phrase "or a related disease or disorder" renders the claim(s) indefinite because it is unclear what diseases or disorders are considered “related” to those previously recited, or what aspects of the diseases or disorders would render them “related” within the scope of the claim, nor is any guidance provided in the specification such that one would be able to ascertain the scope of a “related disease or disorder”.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 33-38 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 33-38 depend directly or indirectly from claim 32. Claims 33-35 recite XRPD peaks associated with the solid Form D of berberine ursodeoxycholate. Claim 36 recites that the solid form is anhydrous. Claim 37 recites that the solid form is a crystalline form. Claim 38 recites that the XRPD of the solid form comprises peaks essentially the same as in Figure 4.
These claims are in improper dependent form for failing to further limit the subject matter of the claim upon which they depend, as the claims merely recite properties that are inherent to the solid form that is Form D of berberine ursodeoxycholate. For example, the XRPD peaks associated with Form D are physical properties of the solid (crystalline) form, such that listing additional peaks in a dependent claim does not limit the XRPD pattern of Form D. Moreover, Form D is necessarily anhydrous as a hydrated or solvated form would not be Form D.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 32, 36, 37, 39-42, 119, 130, 132, 134-135, and 155 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 32 is directed toward a solid form, which is Form D, of berberine ursodeoxycholate, having an X-ray powder diffraction (XRPD) pattern comprising one or more listed peaks. Claim 32, however, is not supported by the instant disclosure for crystal forms of the above compounds or solvates thereof generally. A claimed crystalline polymorph is generally considered adequately described when characterized by at least 3-5 XRPD peaks. See Brittain (2009), page 334. The claim at issue only requires that the solid form be characterized by one peak, which is inadequate in order to ascertain the crystalline structure. Claims 36-37, 39-42, 119, 130, 132, 134-135, and 155 do not set forth the requisite number of XRPD peaks and are also rejected.
Claim 134 is 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 treating or reducing a disease or disorder selected from fatty liver, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), cholestatic liver diseases, graft-versus-host disease of the liver, primary sclerosing cholangitis, chronic viral associated liver diseases, alcohol-related liver diseases, pre-diabetes, diabetes, hyperlipidemia, hypercholesterolemia, diabetic dyslipidemia, dyslipidemia in statin-intolerant patients, and obesity, does not reasonably provide enablement for treating. 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.
As stated in the MPEP 2164.01 (a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
In the instant case, the Wands factors are relevant for the following reasons:
The nature of the invention, state and predictability of the art, and relative skill level.
The nature of the invention claims a pharmaceutical composition comprising a solid form, Form D, of berberine ursodeoxycholate and a method of treating a metabolic disorder, heart disease, neurodegenerative disease, or liver disease with said pharmaceutical composition.
The treatment of neurodegenerative disorder generally cannot possibly be considered enabled.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “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, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added).
Disorders as broad as metabolic disorders and liver diseases further read on and/or overlap in scope with neurodegenerative disorders, such and dementias and cancers.
There is no evidence set forth in the instant application, or in the prior art, that the claimed solid form of berberine ursodeoxycholate can treat such a broad scope of disorders. Despite a high level of skill in the art, that of an MD or PhD, pharmacological activity is a very unpredictable area. In cases involving physiological activity "the scope of the enablement obviously varies inversely with the degree of unpredictability of the factors involved." In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970). Since this case involves unpredictable in-vivo physiological activities, the scope of the enablement given in the disclosure presented here was found to be low.
It is maintained by the examiner that applicant has not enabled the instant claims in view of the current state of the art, as the applicant fails in the specification to demonstrate the ability of the claimed invention to treat a metabolic disorder, heart disease, neurodegenerative disease, or liver disease generally. Furthermore, said diseases have no reasonable expectation to be curable or preventable.
The breadth of the claims
The scope of "neurodegenerative disorder" cannot be deemed enabled. The term "neurodegenerative disorder" covers a broad array of different disorders that have different modes of action and different origins. The term covers such diverse disorders as Alzheimer's Disease; Parkinson's Disease; ALS and variants such as forms of ALS-PDC; Gerstmann-Straussler-Scheinker Disease (GSS); Pick's Disease; Diffuse Lewy Body Disease; Hallervordon-Spatz disease; progressive familiar myoclonic epilepsy; Corticodentatonigral degeneration; progressive supranuclear palsy (Steele-Richardson-Olszewski); Huntington's disease; more than a dozen dementias collectively called "frontotemporal dementia and Parkinsonism linked to chromosome 17" (FTDP-17); Tourette's syndrome; Shy-Drager syndrome; Friedrich's ataxia and other spinocerebellar degenerations; Olivopontocerebellar atrophy (OPCA); spasmotic torticollis; Striatonigral degeneration; various types of torsion dystonia; certain spinal muscular atrophies, such as Werdnig-Hoffmann and Wohlfart-Kugelberg-Welander; Hereditary spastic paraplegia, Primary lateral sclerosis; peroneal muscular atrophy (Charcot-Marie-Tooth); Creutzfeldt-Jakob Disease (CJD); Hypertrophic interstitial polyneuropathy (Dejerine-Sottas); retinitis pigmentosa; Leber's Disease; and Hypertrophic interstitial polyneuropathy. These exhibit a very broad range of effects and origins. For example, some give progressive dementia without other prominent neurological signs, such as Alzheimer's disease, whereas other dementias have such signs, such as Diffuse Lewy Body Disease. Some give muscular wasting without sensory changes, e.g., ALS, and some do have the sensory changes such as Werdnig-Hoffmann. Some are abnormalities of posture, movement or speech, such as Striatonigral degeneration, and other are progressive ataxias, such as OPCA. Some are linked to tau mutations, such as Alzheimer's disease and FTDP-17, and other such as Parkinson's clearly do not. Some affect only vision such as retinitis pigmentosa.
Even within those that fall into the same category of effects, there are often striking differences. For example, Alzheimer's disease and Pick's disease both give progressive dementia without other prominent neurological signs. But the characteristic Alzheimer's neurofibrillary tangles are not seen in Pick's Disease, which has straight fibrils, as opposed to the paired helical filaments of Alzheimer's disease. Pick's Disease gives lobal atrophy, not seen in Alzheimer's disease. There are differences in origins, even with what little is known. Thus, among progressive dementias, CJD is definitely caused by an infectious agent; so far as can be determined, this is not so for Huntington's disease.
Even among hereditary disorders, the origins are different. Thus, FTDP-17 comes from chromosome 17, Huntington's disease from 4, and the neurodegenerative disorder that people with Down's syndrome develop later in life is presumably connected in some way to 21.
The great majority of these have no treatment at all, and of those that do, none or virtually none have been treated with such inhibitors as are disclosed here. The great diversity of diseases falling within the "neurodegenerative disorder" category means that it is contrary to medical understanding that any agent (let alone a genus of trillions of compounds) could be generally effective against such diseases. The intractability of these disorders is clear evidence that the skill level in this art is low relative to the difficulty of the task. Further, what little success there has been does not point in this direction. Thus, what very few treatments that the massive research effort on Alzheimer's disease has produced are means of providing Acetylcholinesterase inhibition, unrelated to the mechanism of action in this case.
As stated above, the scope of metabolic disorders and liver diseases not only encompasses neurodegenerative diseases such as dementias, but also cancers. Different types of cancers affect different organs and have different methods of growth and harm to the body, and different vulnerabilities. The skill thus depends on the particular cancer involved. There are some cancers where the chemotherapy skill level is high and there are multiple successful chemotherapeutic treatments. The mechanism in these situations, however, is not necessarily the same as is alleged for these compounds.
One skilled in the art knows that chemotherapy of brain tumors is especially difficult. This is because 1) the blood-brain barrier, which is often intact in parts or all of a brain tumor, will block out many drugs, as it is the purpose of the blood-brain barrier to protect the brain from alien chemicals, and 2) CNS tumors are characterized by marked heterogeneity, which greatly decreases vulnerability to chemotherapy. As a result, many categories of CNS tumors simply have no chemotherapy available. These include, generally, hemangioblastomas, meningiomas, craniopharyngiomas, acoustic neuromas, pituitary adenomas, optic nerve gliomas, glomus jugulare tumors and chordomas, to name just some. With regard to gliomas, GBM is considered untreatable; no effective agents have emerged for the treatment of GBM, despite 20 years of enrolling patients in clinical trials. It is radiation and surgery which are used for low grade gliomas (e.g. pilocytic astrocytoma and diffuse astrocytomas), as no drug has been found effective. There is no drug treatment established as effective for optic nerve gliomas or gangliogliomas. Indeed, very few gliomas of any type are treated with pharmaceuticals; it is one of the categories of cancer that is the least responsive to drugs.
Lymphomas of the stomach are not commonly treated with anti-cancer agents per se, but instead, surgery or radiation and antibiotic therapy (e.g. amoxicillin, metronidazole, bismuth, and omeprazole) are the primary treatments.
Neuroendocrine tumors of the cervix generally do not respond to chemotherapy.
A number of sarcomas, including alveolar soft part sarcoma (ASPS), retroperitoneal sarcoma, most liposarcomas, and the assorted chondrosarcomas, are generally considered not to respond to chemotherapy; no chemotherapeutic agent has been established as effective
The amount of direction or guidance provided and the presence or absence of working examples
The specification provides no direction or guidance for treating such a broad scope of diseases and disorders. However, the specification (par. [0008]) does contemplate particular diseases contemplated to be treatable using the claimed solid form.
The quantity of experimentation necessary
Due to the known unpredictability in the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that a composition comprising solid form Form D of berberine ursodeoxycholate could be used to treat a metabolic disorder, heart disease, neurodegenerative disease, or liver disease generally.
MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here.
Claim 135 is 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 administering a therapeutically effective amount of a pharmaceutical composition according to claim 119 effective to treat or reduc, does not reasonably provide enablement for administering a therapeutically effective amount of a pharmaceutical composition according to claim 119 effective to prevent a disease or disorder. 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.
It is presumed “prevention” of the claimed diseases and disorders would require a method of identifying those individuals who will develop the claimed diseases before they exhibit symptoms. There is no evidence of record that would guide the skilled clinician to identify those who have the potential of becoming afflicted.
The factors to be considered in making an enablement rejection were summarized above. 1) As discussed above, preventing diseases requires identifying those patients who will acquire the disease before it occurs. This would require extensive and potentially open-ended clinical research on healthy subjects. 2) The scope of the claim includes administering an amount of the composition of claim 119 effective to prevent diseases such as diabetes, non-alcoholic fatter liver disease, and other metabolic diseases or disorders. 3) There is no working example of such a preventive procedure in man or animal in the specification. 4) The claims rejected are drawn to clinical pharmacology and are therefore physiological in nature. 5) The state of the art is that no general procedure is art-recognized for determining which patients generally will suffer from these diseases or disorders before the fact. 6) The artisan using Applicants invention would be a Board-Certified physician with an MD degree, or an individual with a PhD. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting a compound to be effective for the prevention of the aforementioned diseases and disorders. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable for any agent to be able to prevent diabetes, non-alcoholic fatter liver disease, and other metabolic diseases or disorders. That is, the skill is so low that no compound effective generally for the prevention of diabetes, non-alcoholic fatter liver disease, and other metabolic diseases or disorders exists. 7) It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved" and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed diseases.
Claim Rejections - 35 USC § 102/103
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
Claim(s) 119 and 134-135 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Liu (WO 2016/015634 A1; 04 February 2016).
Liu discloses crystalline berberine ursodeoxycholate, which was obtained by purification of crude berberine ursodeoxycholate through crystallization from ethanol and ethyl acetate (p. 59, par. [00223]). Liu discloses a method of treating non-alcoholic fatty liver in mice, comprising administering berberine ursodeoxycolate in 0.5% CMC-Na solution as vehicle (p. 60, Example 5).
The composition of Liu and its use in treating non-alcoholic fatty liver in mice anticipates the instant claims, which encompass embodiments wherein the pharmaceutical composition comprises berberine ursodeoxycholate in a solvent (see the above rejection under 35 U.S.C. 112(b)) which would not be expected to maintain the solid Form D.
Alternatively, the composition comprising Form D of berberine ursodeoxycholate and a pharmaceutically acceptable carrier, excipient, or diluent would be prima facie obvious to one of ordinary skill in the art. MPEP 2112 states:
“SOMETHING WHICH IS OLD DOES NOT BECOME PATENTABLE UPON THE DISCOVERY OF A NEW PROPERTY
The claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).”
In this case, the “unknown property” is the particular crystalline form. This is unknown because the reference is silent on this property. MPEP 2112 goes on to state:
“A REJECTION UNDER 35 U.S.C. 102/103 CAN BE MADE WHEN THE PRIOR ART PRODUCT SEEMS TO BE IDENTICAL EXCEPT THAT THE PRIOR ART IS SILENT AS TO AN INHERENT CHARACTERISTIC
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103, expressed as a 102/103 rejection.”
Again, the “CHARACTERISTIC” which the prior art is silent on is the crystalline form (crystalline form is considered to be in the category of chemical properties; see Zenith Laboratories Inc. v. Bristol-Myers Squibb Co. 30 USPQ2d 1285, 1288).
This is not an ordinary inherency situation where it is not explicitly stated what the product actually is. In every reference applied, the reference explicitly teaches exactly what the compound is. In fact, it is the opposite. In a normal inherency situation, the claim is of known structure, and the reference is of unknown structure. Here, the latter is not true, and hence the legal circumstances of inherency in the prior art do not apply. The only difference is the property about which the reference happens to be silent. Recitation of a property, inherently possessed by the prior art thing, does not distinguish a claim drawn to those things from the prior art, In re Swinehart, 169 USPQ 226, 229.
See for example Ex parte Anderson, 21 USPQ 2d 1241 at 1251, discussion of Rejection E. The claims had “numerical or functional values for certain properties which [the authors of the references] did not measure”. The PTO presented no reasoning as to why the prior art material would have been expected to have those properties. Instead, the decision states, “There is ample precedent for shifting the burden to an applicant to reproduce a prior art product whose final structure or properties are, at least, in part determined by the precise process used in its manufacture.” (page 1253).
In another example, certain claims of Ex parte Raychem Corp. 25 USPQ2d 1265 required a linearity ratio of less than 1.2. The decision notes that neither reference discloses any values of the linearity ratio. The PTO presented no reasoning as to what the ratio would be expected to be in the references. The Decision states: “However, this does not end the inquiry since, where the Patent and Trademark Office is not equipped to perform the needed testing, it is reasonable to shift the burden of proof to Raychem to establish that (1) the argued difference exists….”
And indeed, there have been a number of cases in which applicants have pointed to silence of the prior art with regard to this or that property: In re Pearson, 181 USPQ 641; In re Zierden 162 USPQ 102; In re Lemin, 140 USPQ 273; Titanium Metals Corporation of America v. Banner, 227 USPQ 773; In re Benner, 82 USPQ 49; In re Wilder, 166 USPQ 545; Ex parte Kucera, 165 USPQ 332; General Electric Co. v. Jewel Incandescent Lamp Co., 67 USPQ 155; In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607; In re Parker, 43 USPQ 457. Such efforts to avoid anticipation on that basis invariably failed. Going further, if silence about properties of prior art compounds could be relied on, then one could not reject over references with no utility (see In re Schoenwald, 22 USPQ2d 1671), since applicants could always insert the utility into the claim as a property.
It is well settled that the PTO can require an applicant to establish that a prior art product does not necessarily possess the characteristics of the claimed product when the prior art and claimed products are identical or substantially identical. An applicant's burden under these circumstances was described in In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-434 (CCPA 1977) as follows:
Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. . . . Whether the rejection is based on ‘inherency' under 35 U.S.C. § 102, or ‘prima facie obviousness’ under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products (footnote omitted).
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 § 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.
Claim 119 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 2 of U.S. Patent No. 10,301,303 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 2 of the ‘303 patent is drawn to a pharmaceutical composition comprising an acid-base addition salt of ursodeoxycholic acid and berberine, wherein the salt has a purity equal to or greater than 95%, and a pharmaceutically acceptable carrier, excipient, or diluent.
Claim 2 anticipates instant claim 119, which encompass embodiments wherein the pharmaceutical composition comprises berberine ursodeoxycholate in a solvent (see the above rejection under 35 U.S.C. 112(b)) which would not be expected to maintain the solid Form D.
Alternatively, the composition comprising Form D of berberine ursodeoxycholate and a pharmaceutically acceptable carrier, excipient, or diluent would be prima facie obvious to one of ordinary skill in the art. MPEP 2112 states:
“SOMETHING WHICH IS OLD DOES NOT BECOME PATENTABLE UPON THE DISCOVERY OF A NEW PROPERTY
The claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).”
In this case, the “unknown property” is the particular crystalline form. This is unknown because the reference is silent on this property. MPEP 2112 goes on to state:
“A REJECTION UNDER 35 U.S.C. 102/103 CAN BE MADE WHEN THE PRIOR ART PRODUCT SEEMS TO BE IDENTICAL EXCEPT THAT THE PRIOR ART IS SILENT AS TO AN INHERENT CHARACTERISTIC
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103, expressed as a 102/103 rejection.”
Again, the “CHARACTERISTIC” which the prior art is silent on is the crystalline form (crystalline form is considered to be in the category of chemical properties; see Zenith Laboratories Inc. v. Bristol-Myers Squibb Co. 30 USPQ2d 1285, 1288).
Claims 134-135 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-8 of U.S. Patent No. 10,988,471 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 4-8 of the ‘471 patent are directed toward a method of treating a disease or disorder selected from cholestatic liver disease, diabetes, dyslipidemia, fatty liver disease, metabolic syndrome, nonalcoholic steatohepatitis, obesity, prediabetes, and a diabetic complication, comprising administering to a subject an effective amount of a pharmaceutical composition comprising berberine ursodeoxycholate and a pharmaceutically acceptable excipient, carrier, or diluent.
Claims 4-8 anticipate instant claims 134-135, which encompass embodiments wherein the administered pharmaceutical composition comprises berberine ursodeoxycholate in a solvent (see the above rejection under 35 U.S.C. 112(b)) which would not be expected to maintain the solid Form D.
Alternatively, the composition comprising Form D of berberine ursodeoxycholate and a pharmaceutically acceptable carrier, excipient, or diluent would be prima facie obvious to one of ordinary skill in the art. MPEP 2112 states:
“SOMETHING WHICH IS OLD DOES NOT BECOME PATENTABLE UPON THE DISCOVERY OF A NEW PROPERTY
The claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).”
In this case, the “unknown property” is the particular crystalline form. This is unknown because the reference is silent on this property. MPEP 2112 goes on to state:
“A REJECTION UNDER 35 U.S.C. 102/103 CAN BE MADE WHEN THE PRIOR ART PRODUCT SEEMS TO BE IDENTICAL EXCEPT THAT THE PRIOR ART IS SILENT AS TO AN INHERENT CHARACTERISTIC
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103, expressed as a 102/103 rejection.”
Again, the “CHARACTERISTIC” which the prior art is silent on is the crystalline form (crystalline form is considered to be in the category of chemical properties; see Zenith Laboratories Inc. v. Bristol-Myers Squibb Co. 30 USPQ2d 1285, 1288).
Claims 119, 130, 132, and 134-135 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 16-17, and 21 of copending Application No. 19/770,326 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of the ‘326 application is directed toward a method of treating primary sclerosing cholangitis (PSC) comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising berberine ursodeoxycholate. Claims 16-17 and 21 are directed toward a unit dosage form comprising berberine ursodeoxycholate and a pharmaceutically acceptable carrier, excipient, or diluent, wherein the unit dosage form is in the form of a capsule.
While claims 1 and 16 do not state that the berberine ursodeoxycholate is in the form of solid Form D, in looking to the specification to construe the scope of the claims, paragraph [0080] states, “In certain embodiments, Form D of BUDCA… is employed” and further lists the XRPD peaks corresponding to Form D. As such, one of ordinary skill in the art would be apprised that the claimed invention of the ‘326 application encompasses administration of pharmaceutical compositions wherein the berberine ursodeoxycholate is in the form of Form D.
Regarding the use of the disclosure of the reference patent to construe the scope of the claims, MPEP 804(II)(B)(1) states, “Further, 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). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized ‘that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim,’ but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim.”
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/MADELINE E BRAUN/Examiner, Art Unit 1624 09/10/2026
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