DETAILED ACTION
Claims 1-6, 8, and 11-22 are pending.
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
The instant application filed 5/28/2024 is a National Stage entry of PCT/CN2022/134337, International Filing Date of 11/25/2022 and claims foreign priority to 202111454811.5, filed 12/1/2021.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 8/16/2024 and 8/20/2025, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the Information Disclosure Statements are being considered by the Examiner.
Claim Rejections - 35 USC § 112
(Indefinite)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 5 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 recites the limitation "the fermentation culture" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 6 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 6 recites the limitation "the strain" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites the limitation "the fermentation culture" in line 6. There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites the limitation "the fermentation temperature.” There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites the limitation "the fermentation conditions.” There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites the limitation "the fermentation time.” There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites the limitation "the isolation.” There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites the limitation "the filtration.” There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites the limitation "the extraction,” in both (vii) and (ix) There is insufficient antecedent basis for this limitation in the claim.
Claim 6 recites the limitation "the column chromatography.” There is insufficient antecedent basis for this limitation in the claim.
Claim 6 and 20 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 6 and 20 states, “(i) the strain Streptomyces somaliensis used in the method is purchased from Shanghai Boliang Sci&Tech Co., Ltd;” The commercial source of the strain of organism is ambiguous, as the commercial supplier at the time of purchase could vary over time and the supplier itself does not lead to a concrete definition of the strain. As the product can change over time the claim is indefinite.
Claim 18 is indefinite for being directed to all optional steps, as the entire claim states “if performed” leading to the steps of the claim being optional, and therefore the claim requires no steps.
Claim 20 recites the limitation "the strain" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the fermentation culture" in line 6. There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the fermentation temperature.” There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the fermentation conditions.” There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the fermentation time.” There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the isolation.” There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the filtration.” There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the extraction,” in both (vii) and (ix) There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the column chromatography.” There is insufficient antecedent basis for this limitation in the claim.
Claim 21 is indefinite for being directed to all optional steps, as the entire claim states “if performed” leading to the steps of the claim being optional, and therefore the claim requires no steps.
Claim 22 recites the limitation "the fermentation culture.” There is insufficient antecedent basis for this limitation in the claim.
Claim 22 recites the limitation "the fermentation broth.” There is insufficient antecedent basis for this limitation in the claim.
Claim 22 recites “components Fr. A-Fr. E” It is unclear what applicant is clainming, potentially sequential fractions off the column, but it is unclear as to what this nomenclature means and what each fraction would consist of. The recitation of Fr. B is also not defined, more so since there is Fr. B1 and Fr. B8. A PHOSITA would not be ubale to determine the metes and bound of this recitation. All the “Fr.” Recitaions are ambiguous as to what this recitation is defineing.
Claim 22 recites the limitation "the component Fr. B.” There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 101
(Directed to a Natural Product)
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5, 8, 11-17, and 19 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
The claims recite “natural products” as a limiting element or step without reciting additional elements/steps that integrate the natural principles into the claimed inventions such that the natural products are practically applied, and are sufficient to ensure that the claims amount to significantly more than the natural products themselves. In the instant case, the “natural products” include:
The marine macrocyclic lactams, Somolactam A, B, C and D.
A claim that focuses on natural products or the use of a natural product must also include additional elements or steps to show that the inventor has practically applied, and added something significant to, the natural product/principle itself. See Mayo, 101 USPQ2d at 1966. Patents cannot be obtained on subject matter identified by the courts as being exempted from eligibility (i.e., laws of nature, natural phenomenon, and abstract ideas).
The Mayo framework provides that first whether the claims at issue are directed to a patent-ineligible concept is determined. If the answer is yes, then the elements of each claim both individually and “as an ordered combination” are considered to determine whether additional elements “transform the nature of the claim” into a patent-eligible application. The second step—known as the “inventive concept”—requires that claims include elements which would render the method both new and useful.
The Eligibility Guidance addresses the subject matter eligibility analysis for all claims (i.e., machine, composition of matter, manufacture and process claims). The analysis is to be used for evaluating whether a claim is drawn to patent-eligible subject matter.
Step 1 determines whether the claim is directed to a process, machine, manufacture, or composition of matter. If the claim is directed to a statutory category, proceed to Step 2.
Step 2 is the two-part analysis from Alice Corp. (also called the Mayo test) for claims directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions).
In Step 2A, determine whether the claim is directed to a law of nature, a natural phenomenon, or an abstract idea (judicial exceptions). “Directed to” means the exception is recited in the claim, i.e., the claim sets forth or describes the exception. If yes, Step 2B determines whether the claim as a whole amounts to significantly more than the exception.
Claim elements that are not judicial exceptions include the acts of determining, measuring, comparing to other values, a generic quantitative assay, and a generic kit. The latter two are generic since they are not claimed with limitations that specify they use or contain a specific reagent (e.g. a specific antibody). According to the most recent guidance, to be patent-eligible, a claim that is directed to a judicial exception must include additional features to ensure that the claim describes a process or product that applies the exception in a meaningful way (Federal Register, Vol. 79, No. 241, 12/16/2014, Pg. 74624, Column 1, Paragraph, final). In other words, does the claim amount to significantly more than the exceptions themselves (Federal Register, Vol. 79, No. 241, 12/16/2014, Pg. 74624, Column 1, Paragraph, final). Limitations that were found not to be significantly more when recited in a claim with a judicial exception include well-understood, routine, and conventional activities previously known to the industry and specified at a high level of generality (Federal Register, Vol. 79, No. 241, 12/16/2014, Pg. 74624, Column 3, Paragraph, first).
Recently, in Univ of Utah v Ambry v Myriad (Fed Cir 2014) the court looked to the claims to find any “non-patent-ineligible elements” sufficient to “transform the nature of the claim into a patent-eligible application.” Here, the claims require various physical transformations, including hybridizing the gene probe; amplification of the gene; and sequencing the gene. However, according to the appellate panel, those transformations are insufficient - primarily because those steps “set forth well-understood, routine and conventional activity engaged in by scientists at the time of Myriad’s patent applications” and are the activities that a scientist would have relied upon to achieve the goals of the invention. In the present case, the active method steps set forth well-understood routine and conventional activity engaged in by scientists and are the activities that a scientist would have relied upon to achieve the goals of the invention.
The Court in in Ariosa Diagnositcs vs Sequenom. (2014-1139, 2014-1144) reiterated the two-step analysis required by Mayo and Alice,namely "determin[ing] whether the claims at issue are directed to a patent-ineligible concept" and, if so, "consider[ing] the elements of each claim both individually and ’as an ordered combination' to determine whether additional elements 'transform the nature of the claim' into a patent-eligible application the court went on to point out that the claimed method "begins and ends with a natural phenomenon," i.e., the presence of cffDNA in maternal blood and the diagnostic implications that can be made by correlating that cffDNA with paternally inherited nucleic acid. Thus, the court concluded that the claims of the '540 patent satisfy the first step of the analysis laid out in Alice because they are "directed to matter that is naturally occurring." The Court next evaluated the second step of the analysis to determine whether the remaining elements of the claims in the '540 patent "transform" the natural phenomenon into a patent-eligible application. Despite the presence of claims to particular methods for amplifying, detecting, and correlating cffDNA with paternally inherited nucleic acid, the Court concluded that the claims were insufficient to integrate the naturally occurring material into a patent-eligible application. The Court stated that the method steps involving standard PCR amplification and gel electrophoresis are “not new and useful.” Thus, the specific methods recited in the claims were considered "routine and conventional.”
The Federal Circuit also addressed preemption and found that because these method claims were deemed subject matter ineligible, the concern of preemption, i.e., whether the methods preclude alternative methods in the same field but outside the scope of the claims, was moot. The Court further stated that "[w]hile preemption may signal patent ineligible subject matter, the absence of complete preemption does not demonstrate patent eligibility. The Court further noted that "[w]here a patent's claims are deemed only to disclose patent ineligible subject matter under the Mayo framework, as they are in this case, preemption concerns are fully addressed and made moot."
The Court rejected Sequenom’s arguments that the claimed methods would not preclude alternative methods, and, therefore, would not preempt the field. The Court explained that the questions of preemption are inherent in subject matter eligibility analysis, and when the claims fail the Mayo test, the question of preemption would not arise.
The present claims are directed to a product and a process so Step 1 is satisfied.
The present claims are directed to a judicial exceptions. The claims recite “natural products” as a limiting element, (Somolacatms A, B, C, and D and their inherent properties)
The next step, STEP 2B, is to determine whether the claim as a whole recite something significantly different than the judicial exception(s). While considering that additional claim elements that are well-understood, routine, and conventional in this art are not significant.
Claims 1-4 are directed to the chemical structure of Somolacatms A, B, C, and D and noting else. These claims do not recite anything different from the natural product, as such they do not pass step 2B and are not patent eligible.
Claim 5 is directed to a method for preparing the natural products comprising the following step: isolating the compound from the fermentation culture of Streptomyces somaliensis. In this case, a generic step of “isolating the compound” is not significant, as there is no defined required technique, the claim simply requires one to use any known technique to acquire the product and therefore this claim does not pass step 2B.
Claim 8 is directed to a pharmaceutical composition of the natural product and a pharmaceutical adjuvant. The Specification states, [0170] The term “pharmaceutical adjuvant” refers to excipients and additives used in the production of drugs and formulation of prescriptions, and is all substances contained in a pharmaceutical preparation except for active ingredients. For details, see Pharmacopoeia of the People's Republic of China (2020 Edition) or Handbook of Pharmaceutical Excipients (Raymond C Rowe, 2009). Therefore this is directed to anything in the pharmaceutical art that in not an active ingredient, for example, water. Therefore there is nothing significant about the addition of the pharmaceutical adjuvant and the claim does not pass step 2B.
Claims 11-12 and 14 are directed to the inherent property of the natural product, as the claim simply requires, “An IL-6 inhibitor, comprising the macrocyclic lactam compound.” This however is simply stating the inherent property of the compound itself, and therefore is not adding anything to the compound at all, this is just a recitation of the property which is inseparable from the compound itself. Therefore there is nothing significant about the addition of the recitation and the claim does not pass step 2B.
Claims 13 and 15 also state, “for use in vitro.” The addition of an intended use to the end of the claim does not add any limitation to the claim, as the intended use is just there to inform the public to the use of the compound and does not require any additional structure to the compound. Therefore there is nothing significant about the addition of the “intended use” and the claim does not pass step 2B.
Claim 16 is directed to a method for treating an anti-inflammatory, comprising the macrocyclic lactam compound. Claim 16 has not steps to the claim, the method is in the preamble only. There is no administration step, and therefore the claim is not adding anything to consider. Therefore there is nothing significant about the addition of the “intended use” and the claim does not pass step 2B.
Claim 17 is directed to a method for treating an anti-inflammatory, comprising the macrocyclic lactam compound of claim 4. Claim 17 has not steps to the claim, the method is in the preamble only. There is no administration step, and therefore the claim is not adding anything to consider. Therefore there is nothing significant about the addition of the “intended use” and the claim does not pass step 2B.
Claim 19 is directed to a method for preparing the macrocyclic lactam compound of claim 4, comprising the following step: isolating the compound from the fermentation culture of Streptomyces somaliensis. In this case, a generic step of “isolating the compound” is not significant, as there is no defined required technique, the claim simply requires one to use any known technique to acquire the product and therefore this claim does not pass step 2B.
All of the additional claim elements listed are well-understood, routine, and conventional in this art.
In sum, when the relevant factors are analyzed, they weigh against the present claims amounting to significantly more than the judicial exceptions themselves. Accordingly, the claims do not qualify as eligible subject matter.
Claim Rejections - 35 USC § 112
(Scope of Enablement)
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 1-3, 5-6, 8, 12-13, 16, and 18 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 the compounds defined in claim 4 (Somolacatms A, B, C, and D and their salts), does not reasonably provide enablement for the chemical structures defined in claims 1-3, their isolation, and the methods of using them in a treatment. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
All questions of enablement are evaluated against the claimed subject matter. When considering whether claims in a utility patent application or patent are enabled, USPTO personnel will use the Wands factors to ascertain whether the amount of experimentation required to enable the full scope of the claimed invention is reasonable. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). See also MPEP § 2164.01(a). The focus of the examination inquiry is whether everything within the scope of the claim is enabled. Accordingly, the first analytical step requires that the examiner determine exactly what subject matter is encompassed by the claims. See, e.g., AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244, 68 USPQ2d 1280, 1287 (Fed. Cir. 2003) (When a range is claimed, there must be reasonable enablement of the scope of the range. Here, the claims at issue encompassed amounts of silicon as high as 10% by weight, however the specification included statements clearly and strongly warning that a silicon content above 0.5% by weight in an aluminum coating causes coating problems. Such statements indicate that higher amounts will not work in the claimed invention.). The examiner should determine what each claim recites and what the subject matter is when the claim is considered as a whole, not when its parts are analyzed individually. No claim should be overlooked. With respect to dependent claims, 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, fourth paragraph, should be followed. These paragraphs state "a claim in a dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers" and requires the dependent claim to further limit the subject matter claimed.
Applicant has isolated 4 compounds from the fermentation of Streptomyces somaliensis. Applicant has determined the compounds to inhibit IL-6, and therefore has enabled them is the use of treating diseases that would be treated with an IL-6 inhibitor.
Applicant has not synthesized or isolated any derivatives of these 4 compounds.
(A) The breadth of the claims.
Applicant has claimed a generic structure with over 20 variables (R Groups with around 20 different generic options, when extrapolated out for compounds would be hundreds of options at one position), in combination with 5 distinct Linkers (L1 Group and L2 Groups, with their own R groups). The scope of the claimed compounds on the generously small end is around 335 quintillion trillions (3.35 x 1025). More likely this claimed scope is 1 x 1060). This is still generous as the when one considers the diastereomers, the number would be increased substantially.
(B) The nature of the invention.
Applicant’s claims are directed to pharmaceutical compounds and their inherent properties of inhibiting IL-6. The compounds are novel and their synthesis is not established, therefore the nature of the invention is complex and pioneering, requiring more disclosure as there is no routine practice in this field.
(C) The state of the prior art.
There is no prior art in these natural products. Applicant is the only one to isolate these macrolactams from Streptomyces somaliensis.
(D) The level of one of ordinary skill.
The ordinary skill is high, as one would be a PhD holding medicinal chemist or PhD holding biologist.
(E) The level of predictability in the art.
The pharmaceutical art is highly unpredictable with a failure rate around 99%. The synthesis of natural products is a multi-year endeavor with substantial trial an error as one is unable to determine an efficient synthetic route to the compound of distinct structure and complex stereochemistry. Then one would need to predict which compounds would have the IL-6 inhibition, which is unpredictable without experimentation.
(F) The amount of direction provided by the inventor.
Applicant has not provided any synthetic guidance. Applicant has not synthesized a single compound. Applicant has not tested any compound outside the 4 compounds of natural origin.
(G) The existence of working examples.
There are 4 working examples, this is the scope Applicant is enabled for.
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In order to make and use the entire scope of the invention, one would need thousands of chemists working over nearly a decade to synthesize a portion of the claimed subject matter.
Allowable Subject Matter
There is no prior art on the marine macrocyclic lactams, Somolactam A, B, C and D. A claim directed to a method of combating inflammation in a subject comprising administration of a therapeutically effective amount of Somolactam A, B, C or D (or salts thereof) to the subject, wherein the therapeutically effective amount inhibits IL-6, would be allowable.
Potentially the method of isolation of Somolactam A, B, C and D could be allowable if Applicant where to design a claim to capture the defined Streptomyces somaliensis, the actual fermentation conditions, and the actual purification method. This would require specific steps and specific conditions.
Closest Prior Art
The closest art is:
Hou, L., Huang, H., Li, H. et al. Overexpression of a type III PKS gene affording novel violapyrones with enhanced anti-influenza A virus activity. Microb Cell Fact 17, 61 (2018). https://doi.org/10.1186/s12934-018-0908-9
Hou is directed to making and isolating a different polyketides, violapyrones, from deepsea-derived Streptomyces somaliensis SCSIO ZH66. There is overlap in the fact they are after polyketides, and are using Streptomyces somaliensis. However, they do not isolate Somolactam and do not discuss this polyketide.
Huang, H.; Li, H.; Qiu, Y.; Hou, L.; Ju, J.; Li, W. A New Dioic Acid from a wbl Gene Mutant of Deepsea-Derived Streptomyces somaliensis SCSIO ZH66. Mar. Drugs 2016, 14, 184. https://doi.org/10.3390/md14100184
Huang is directed to making and isolating a new Dioic Acid from a wbl Gene Mutant of deepsea-derived Streptomyces somaliensis. There is overlap in the fact they are after natural products, and are using Streptomyces somaliensis. However, they do not isolate Somolactam and do not discuss this polyketide.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL J SCHMITT whose telephone number is (571)270-7047. The examiner can normally be reached M-F 8-6 MidDay Flex.
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/MICHAEL J SCHMITT/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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