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
Claims 1-15 are currently pending in the instant application. Applicants have amended claims 1, 3-7 and 9-15 in an amendment filed on April 14, 2025. Claims 1-6, 10, 11 and 13-15 are rejected and claims 7-9 and 12 are objected in this Office Action.
I. Priority
The instant application is a 371 of PCT/EP2023/054926, filed on February 28, 2023 and claims benefit of Foreign Application EPO 22159261.1, filed on February 28, 2022.
II. Information Disclosure Statement
The information disclosure statements (IDS) submitted on August 28, 2024 and November 7, 2025 are compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
III. Rejections
Claim Rejections - 35 USC § 102
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.
Claims 1-3, 10, 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Registry No. 2375258-67-4. The instant invention claims
PNG
media_image1.png
819
783
media_image1.png
Greyscale
PNG
media_image2.png
145
694
media_image2.png
Greyscale
The Registry No. 2375258-67-4 teaches the compound
PNG
media_image3.png
261
359
media_image3.png
Greyscale
wherein R1, R2 and R3 are F; X is O; R4 is
PNG
media_image4.png
174
163
media_image4.png
Greyscale
and R5 is absent. This species of compound anticipates the genus compound of the instant invention, wherein the genus structure and its definitions are stated above.
Claims 1, 2, 10 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Registry No. 2352546-15-5. The instant invention claims
PNG
media_image1.png
819
783
media_image1.png
Greyscale
PNG
media_image2.png
145
694
media_image2.png
Greyscale
The Registry No. 2375258-67-4 teaches the compound
PNG
media_image5.png
249
389
media_image5.png
Greyscale
wherein one of R1, R2 and R3 is H and the other two are F; X is O; R4 is
PNG
media_image4.png
174
163
media_image4.png
Greyscale
and R5 is absent. This species of compound anticipates the genus compound of the instant invention, wherein the genus structure and its definitions are stated above.
Claims 1-3, 6, 10, 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen, S. (abstract) (Chromatographia 2004, 59(11/12), 697-703) (retrieved from DATABASE CAPLUS) . The instant invention claims
PNG
media_image1.png
819
783
media_image1.png
Greyscale
PNG
media_image2.png
145
694
media_image2.png
Greyscale
The Registry No. 438056-07-6 teaches various amino acid derivatives such as the compound
PNG
media_image6.png
220
316
media_image6.png
Greyscale
wherein R1, R2 and R3 are H; X is N; R4 is Ph and R5 is hydrogen. This species of compound anticipates the genus compound of the instant invention, wherein the genus structure and its definitions are stated above.
Claims 1-5, 10, 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Doyel, et al. (abstract) (Journal of the Chemical Society (1962) 1440-4 (retrieved from DATABASE CAPLUS) . The instant invention claims
PNG
media_image1.png
819
783
media_image1.png
Greyscale
PNG
media_image2.png
145
694
media_image2.png
Greyscale
The Registry No. 76313-08-1 teaches various amino acid derivatives such as the compound
PNG
media_image7.png
122
241
media_image7.png
Greyscale
wherein one of R1, R2 and R3 is C4 alkyl and the other two are H; X is O; R4 is -CH2Ph and R5 is absent. This species of compound anticipates the genus compound of the instant invention, wherein the genus structure and its definitions are stated above.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 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 13-15 are rejected under 35 U.S.C. 112 (a), because the specification, while being enabling for a method of treatment of the various diseases listed in claim 13 does not reasonably provide enablement for a method of prevention of these diseases. 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 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 need 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 nature of the invention
The nature of the invention is
PNG
media_image8.png
247
752
media_image8.png
Greyscale
Support for the intended use is in vitro data for Inhibition of sortilin on pages 38-39 of the specification.
The state of the prior art and the predictability or lack thereof in the art
The state of the prior art is that the pharmacological art involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific disease by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The instant claimed invention is highly unpredictable as discussed below:
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instant claimed invention is highly unpredictable since one skilled in the art would recognize that in regards to therapeutic effects of any condition mediated by the inhibition of sortilin, whether or not the condition is affected by the instant compounds’ activity would make a difference.
For example, Applicants’ claim is drawn to a method of preventing cancer. The state of the prior art is that cancer therapy remains highly unpredictable. The various types of cancers have different causative agents, involve different cellular mechanisms, and consequently, differ in treatment protocol. Cancer is a disease characterized by a population of cells that grow and divide without respect to normal limits, invade and destroy adjacent tissues, and may spread to distant anatomic sites through a process called metastasis (URL:http://en.wikipedia.org/wiki/ Cancer>). Most cancers are named for where they start. For example, lung cancer starts in the lung, and breast cancer starts in the breast. Symptoms and treatment depend on the cancer type and how advanced it is (URL: <http://www.nlm.nih.gov/medlineplus/cancer. html>>).
It is known that the challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types, that cancer classification has been based primarily on morphological appearance of the tumor and that tumors with similar histopathological appearance can follow significantly different clinical courses and show different responses to therapy (Golub et al. page 531). Treatment may include surgery, radiation, chemotherapy, immunotherapy, monoclonal antibody therapy, etc. Furthermore, it is known that chemotherapy is most effective against tumors with rapidly dividing cells and that cells of solid tumors divide relatively slowly and chemotherapy is often less effective against them. It is also known in the prior art (Lala et al. page 91) that the role of NO in tumor biology remains incompletely understood with both the promotion and inhibition of NO mentioned for the treatment of tumor progression and only certain human cancers may be treated by selected NO-blocking drugs. These example shows that there are different cellular mechanisms, the unpredictability in the art and the different treatment protocols. Because "cancer" refers to a class of diseases, it is unlikely that there will ever be a single "treatment for cancer".
There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The amount of direction or guidance present and the presence or absence of working examples
The only direction or guidance present in the instant specification is minimal for prevention. There are no working examples present for preventing all of the various diseases embraced by the instant claimed invention.
Test assays and procedure are provided in the specification such as in vitro data for Inhibition of sortilin on pages 38-39.
Receptor activity is generally unpredictable and the data provided is insufficient for one of ordinary skill in the art in order to extrapolate to the other compounds of the claims. It is inconceivable as to how the claimed compounds can treat the extremely difficult diseases embraced by the instant claims.
Applicants have not provided any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use of the instant compounds. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.” See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The breadth of the claims
The breadth of the claims is
PNG
media_image9.png
247
752
media_image9.png
Greyscale
The quantity of experimentation needed and the level of the skill in the art
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine what diseases would be benefited by the effects of inhibiting sortilin and would furthermore then have to determine which of the claimed compounds in the instant invention would provide treatment or prevention of the diseases.
The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro or in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated by the compound encompassed in the instant claims, with no assurance of success.
This rejection can be overcome, for example, by amending the claim to read on the subject matter that Applicants' specification are enabled for as indicated above. Applicants are suggested to delete the term “prevention” in the rejection claims.
Claim Rejections - 35 USC § 112
The following is a quotation of the second paragraph of 35 U.S.C. 112:
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 13-15 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. Regarding claims 13-15 , 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).
Claims 14-15 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. Regarding claims 14-15, the phrase "preferably" 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).
V. Objections
Dependent Claim Objections
Dependent Claims 7-9 and 12 are objected to as being dependent upon a rejected based claim. To overcome this objection, Applicant should rewrite said claims in an independent form and include the limitations of the base claim and any intervening claim.
VI. Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Shawquia Jackson whose telephone number is 571-272-9043. The examiner can normally be reached on 7:00 AM-3:30PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Adam Milligan can be reached on 571-270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
/SHAWQUIA JACKSON/Primary Examiner, Art Unit 1626
Prosecution Insights