Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
This Office Action is a response to Applicant’s Preliminary Amendment filed October 25, 2024.
Claims 12 and 13 have been canceled. New claims 16-19 are acknowledged. Claims 1-10, 14 and 15 have been amended.
Claims 1-11 and 14-19 are pending in the instant application.
Claims 1-11 and 14-19 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed April 5, 2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
The listing of references in the specification at pages 61 and 62 is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Priority
Acknowledgment is made of Applicant's claim for foreign priority based on EU 22168132.3, filed April 13, 2022 and EU 21201765.1, filed October 8, 2021. The certified copies have been placed in the file.
Drawings
The Drawings filed April 5, 2024 are acknowledged and have been accepted by the Examiner.
Claim Rejections - 35 USC § 112
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 1-11 and 14-19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
The claims are indefinite because the term, “ADAMTS14” is not clearly defined. Since abbreviations often have more than one meaning, it is suggested that inserting the full name of the ADAM Metallopeptidase with Thrombospondin Type 1 Motif 14 would be appropriate.
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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 1-10 and 14-17 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 fibrosis in a subject, comprising administering to a subject in need thereof a therapeutically- or prophylactically-effective amount of an ADAMTS14 inhibitor, does not reasonably provide enablement for a method of preventing fibrosis in a subject, comprising administering to a subject in need thereof a therapeutically- or prophylactically-effective amount of an ADAMTS14 inhibitor. 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/or use the invention commensurate in scope with these claims. This is a scope enablement rejection.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988).
Wands states on page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
It should be made clear that, the enabling specification must teach those skilled in the art to make and use the full scope of the claimed invention without undue experimentation. “Although not explicitly stated in section 112, to be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without "undue experimentation." Vaeck, 947 F.2d at 495, 20 USPQ2d at 1444; Wands, 858 F.2d at 736-37, 8 USPQ2d at 1404; In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (the first paragraph of section 112 requires that the scope of protection sought in a claim bear a reasonable correlation to the scope of enablement provided by the specification).” In re Wright (CAFC) 27 USPQ2d 1510 at 1513.
The nature of the invention. The claims are drawn to a method of treating or preventing fibrosis in a subject, comprising administering to a subject in need thereof a therapeutically- or prophylactically-effective amount of an ADAMTS14 inhibitor. Therefore, the invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
Guidance in the Specification and working examples. The present Specification teaches, the ADAMTS14 inhibitor of the invention is for use in cystic fibrosis, for example. See claims 3, 5, 8, 10 and Numbered Paragraphs 5 and 12. The art is clear that you cannot prevent cystic fibrosis. See Cleveland Clinic, Cystic Fibrosis downloaded from Cystic Fibrosis: Causes, Symptoms & Treatment on July 27, 2026.
Also, the present Specification teaches, the ADAMTS14 inhibitor of the invention is for use in idiopathic pulmonary fibrosis (IPF), for example. See claims 3, 5, 8, 10 and Numbered Paragraphs 5 and 12. The art is clear that IPF can’t be prevented. See Cleveland Clinic, Pulmonary Fibrosis downloaded from Pulmonary Fibrosis: Causes, Symptoms & Treatment on July 27, 2026.
The breadth of the claims. The claims are so broad to include a method of preventing any fibrosis, however, not all fibrosis diseases and disorders are preventable. While certain types linked to lifestyle, environment, or specific medications can be avoided or reduced, many forms arise from genetic factors, autoimmune conditions, or unknown causes (idiopathic) where prevention is currently impossible.
The unpredictability of the art and the state of the prior art. The data presented in the Specification does not rise to the level of prevention of any/all fibrosis in a subject. Regarding “preventing” disorder/disease, it is noted that “preventing” encompasses complete (i.e., 100%) and permanent prevention. One of skill in the art would recognize that the complete prevention of any/all fibrosis in a subject would be very difficult and there would be a low level of expectation of success (i.e., highly unpredictable).
One of skill in the art would recognize that to make and use an ADAMTS14 inhibitor for preventing fibrosis in a subject, there would be a low level of expectation of success (i.e., highly unpredictable) as evidenced by the Cleveland Clinic disclosures supra.
The specification does not provide any working example demonstrating a method of preventing fibrosis in a subject, comprising administering to a subject in need thereof a therapeutically- or prophylactically-effective amount of an ADAMTS14 inhibitor. Therefore, given the lack of knowledge present in the prior art and the lack of guidance provided in the Specification with respect to preventing fibrosis, further experimentation would be required. Considering that the additional experimentation would require de novo experimentation without a guarantee of success, and further considering that any positive results (i.e., successful disease prevention in a subject) would amount to a significant advancement in the state of the art, the additional experimentation required is considered undue.
The quantity of experimentation. The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
Furthermore, in In re Vaeck, 947 F.2d 488,495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991), the Court ruled that a rejection under 35 U.S.C. 112, first paragraph for lack of enablement was appropriate given the relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. Such is the case here where there is a relatively incomplete understanding in the biotechnological field involving preventing certain fibrosis disease and disorder, as described above, and the lack of a reasonable correlation between the narrow disclosure in the Specification and the broad scope of protection sought in the claims.
Without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention. Therefore, it is appropriate to reject the claims under 35 USC 112(a) for not being enabled over the scope claimed.
Thus, in view of the breadth of the claims, the lack of guidance, and the lack of working examples, the instant specification is not found to be enabling for a method of preventing fibrosis in a subject, comprising administering to a subject in need thereof a therapeutically- or prophylactically-effective amount of an ADAMTS14 inhibitor. It would require undue experimentation and making a substantial inventive contribution for the skilled artisan to discover how to make and/or use the claimed invention in its full scope.
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Claims 1-11 and 14-19 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. This is a written description rejection.
The following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirement for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice..., reduction to drawings..., or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the disclosure must provide written support for the entire scope of the genus. Support for a genus is generally found where the Applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed and that applicant was in possession of the claimed genus.
The instant claims are drawn to a method of treating or preventing fibrosis in a subject, comprising administering to a subject in need thereof a therapeutically- or prophylactically-effective amount of an ADAMTS14 inhibitor. Some claims are drawn to a method of inhibiting TGFb1-mediated signalling or YAP-mediated signalling in a cell, comprising contacting a cell with an ADAMTS 14 inhibitor. As discussed below, there is insufficient written description for the ADAMTS14 inhibitor encompassed by the claims.
The Specification discloses:
Agents capable of binding to and inhibiting the activity of ADAMTS14 may e.g. be peptides/polypeptides, nucleic acids or small molecules; and
Inhibitory nucleic acid selected from: an siRNA, dsiRNA, miRNA, shRNA, pri-miRNA, pre-miRNA, saRNA, snoRNA, and an antisense oligonucleotide
The instant Specification provides examples of siRNA-mediated knockdown of expression of ADAMTS14 in lung fibroblast cells. See Examples 1 and 2, for example. NOTE: The present Specification discloses:
In some embodiments, the antisense nucleic acid comprises, or consists of, the nucleotide sequence of the guide strand of an siRNA of Smart Pool Cat. No. L-00576-00-0005 (Dharmacon);
In some embodiments, the antisense nucleic acid comprises, or consists of, the nucleotide sequence of the guide strand of an siRNA of siGENOME Human ADAMTS14 siRNA Cat. No. D-005765-01 (Dharmacon).; and
In some embodiments, the antisense nucleic acid comprises, or consists of, the nucleotide sequence of the guide strand of an siRNA of siGENOME Human ADAMTS14 siRNA Cat. No. D-005765-03 (Dharmacon).
Other than the three Dharmacon references above, no actual ADAMTS14 nucleic acid inhibitor sequence has been disclosed in the present invention.
The prior art teaches that nucleic acid encoding ADAMTS14, or alternatively its complementary strand, may be useful for the treatment of a wide range of diseases, including fibrosis. See WO 03/042379 A2 (submitted and made of record on the IDS filed April 5, 2024). NOTE: WO 03/042379 does not disclose an actual ADAMTS14 nucleic acid inhibitor sequence.
There is insufficient written description of the ADAMTS14 inhibitors encompassed by the claims because there is a substantial variation within the genus of inhibitors and the few species which carry out the functionality of the instant claims does not adequately describe or represent the entire genus of ADAMTS14 inhibitors. Only siRNA nucleic acid inhibitors have been reduced to practice.
The written description requirement for claims that require an inhibitor ADAMTS14 to treat or prevent fibrosis in a subject is not met because the claims encompass a genus of ADAMTS14 inhibitors which are not adequately described.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
To satisfy the written description requirement an applicant must describe the invention is such a way as to convey to one skilled in the art that applicant had the invention in his possession when the application was filed. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). In cases such as the instant application where a genus is claimed, the specification must contain “either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 1350. However, written description requirement for claims that recite an ADAMTS14 inhibitor that treats or prevents fibrosis in a subject is not met.
The entire genus of ADAMTS14 inhibitors that treat or prevent fibrosis in a subject that function as claimed does not exist in the instant application. That is, adequate written description support does not exist to practice the full scope of the invention claimed. The specification nor the art discloses neither a representative number of species inhibitors nor any structure/function correlation that would enable one of skill to immediately envision the genus of ADAMTS14 inhibitors to treat or prevent fibrosis in a subject required to practice the full scope of the invention. Only siRNA nucleic acid inhibitors have been reduced to practice.
The above position is further supported by In re Clarke, 148 USPQ 665, (CCPA 1966), which held that;
“It appears to be well settled that a single species can rarely, if ever, afford support for a generic claim. In re Soll, 25 C.C.P.A. (Patents) 1309, 97 F.2d 623, 38 USPQ 189; In re Wahlforss et al., 28 C.C.P.A. (Patents) 867, 117 F.21 270, 48 USPQ 397. The decisions do not however fix any definite number of species which will establish completion of a generic invention and it seems evident therefrom that such number will vary, depending on the circumstances of particular cases. Thus, in the case of a small genus such as halogens, consisting of four species, a reduction to practice of three, or perhaps even two, might serve to complete the generic invention, while in the case of a genus comprising hundreds of species, a considerably large number of reductions to practice would probably be necessary.”
As stated above, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic claim. Given the breadth of the claims, the Specification lacks sufficient variety of species to reflect the variance in the genus.
In conclusion, the Specification and the prior art as filed does not provide sufficient descriptive support for the myriad of ADAMTS14 inhibitors embraced by the claims. For the reasons discussed above, the 35 USC § 112 rejection for written description is applicable.
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.
Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-11 and 14-19 are rejected under 35 U.S.C. 103 as being unpatentable over WO 03/042379 A2 (submitted and made of record on the IDS filed April 5, 2024).
The claims are drawn to a method of treating or preventing fibrosis in a subject, comprising administering to a subject in need thereof a therapeutically- or prophylactically-effective amount of an ADAMTS14 inhibitor. Claims 11, 18 and 19 are drawn to a method of inhibiting TGFb1-mediated signalling or YAP-mediated signalling in a cell, comprising contacting a cell with an ADAMTS 14 inhibitor.
WO 03/042379 teach a nucleic acid encoding ADAMTS14, or alternatively its complementary strand, may be useful for the treatment of a wide range of diseases, including fibrosis. See (cf. 01, paragraph 16, claims 12, 13, 16 and 21-23). WO 03/042379 teach the ADAMTS14 inhibitor of their invention is an inhibitory nucleic acid, such as antisense oligonucleotides or a siRNA.
WO 03/042379 teach the diseases that can be treated by the ADAMTS14 inhibitor of their invention include, chronic obstructive pulmonary disease (COPD); diseases of the lung; asthma; acute respiratory distress syndrome (ARDS); myocardial infarction; congestive heart failure; Crohn's disease; Alzheimer's disease; and atherosclerosis (including atherosclerotic plaque rupture).
Regarding claims 11, 18 and 19, while WO 03/042379 does not explicitly teach that administration of an antisense or a siRNA ADAMTS14 inhibitor will inhibit TGFb1-mediated signalling or YAP-mediated signalling in a cell, WO 03/042379 teach the exact same method as presently claimed. Namely, a method comprising contacting a cell with an ADAMTS 14 inhibitor. Therefore, any underlying mechanism of action would naturally flow and be inherent to administration of the ADAMTS14 inhibitor to the cell. See MPEP 2112 as it relates to inherency.
Furthermore, the instant specification serves as evidence of record establishing this inherency. Failure of those skilled in the art to contemporaneously recognize an inherent property (i.e. a biological mechanism of action) of a prior art reference does not preclude a finding of anticipation. Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342, 1349, 51 USPQ2d 1943, 1948 (Fed. Cir. 1999). See also Ex parte Novitski, 26 USPQ2d 1389 (Bd. Pat. App. & Inter. 1993).
Note that the Office does not have the facilities and resources to provide the factual evidence needed in order to determine that the method of treating or preventing fibrosis in a subject, comprising administering to a subject in need thereof a therapeutically- or prophylactically-effective amount of an ADAMTS14 inhibitor taught, suggested and motivated by WO 03/042379 would inhibit TGFb1-mediated signalling or YAP-mediated signalling in a cell as presently claimed. In the absence of evidence to the contrary, the burden is upon the Applicant to prove that the presently claimed method is any different from the method taught and suggested by the prior art such that method of the prior art cannot have the intended use/functionality, thereby establishing patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ2d 1922(PTO Bd. Pat. App. & Int. 1989).
The Examiner has provided sound basis in fact and technical reasoning that reasonably supports the determination that the allegedly inherent characteristic necessarily flows from what has been specifically disclosed within the prior art and has shifted the burden to Applicant to provide evidence to the contrary.
Before the effective filing date of the claimed invention, a method of treating or preventing fibrosis in a subject, comprising administering to a subject in need thereof a therapeutically- or prophylactically-effective amount of an ADAMTS14 inhibitor was taught and suggested by the prior art of WO 03/042379.
Starting from WO 03/042379, a person of ordinary skill in the art would have had the incentive to investigate the suitability of ADAMTS14 inhibitors such as antisense and siRNA molecules in the treatment of fibrotic diseases, thereby arriving at the presently claimed subject matter.
Therefore, the subject matter of claims 1-11 and 14-19 is obvious over WO 03/042379, absent some evidence to the contrary.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635
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