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
Status of the Claims
Claims 1-11 and 14-16 are pending in this application.
Claims 1-11 and 14-16 are presently under consideration.
Specification
The disclosure is objected to because of the following informalities: The compound of formula (IV) on page 4, shows a cell-cell-penetrating peptide. Said structure should be amended to strike out the word “cell” from the claimed “cell-cell-penetrating peptide”. Appropriate correction is required.
Claim Objections
Claims 2 and 14-15 are objected to because of the following informalities: The compound of formula (IV) in claim 2, shows a cell-cell-penetrating peptide. The claim should be amended to strike out the word “cell” from the claimed “cell-cell-penetrating peptide”. Claim 14 should be amended to recite “A method for preventing or treating an eye disease”. Claim 15 should be amended to recite “The method according to claim 14, wherein the eye disease is selected”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 14-16 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 treatment of retinoblastoma, does not reasonably provide enablement for the prevention of retinoblastoma and for the treatment or prevention of all the eye diseases claimed in claims 14-15. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The MPEP states:
“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.” These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.”
(A) The breadth of the claims; and (B) The nature of the invention;
The claims are drawn to a method for preventing or treating eye diseases comprising administering a compound of formula (II).
(C) The state of the prior art;
Harvard health (downloaded from URL:<https://www.health.harvard.edu/cancer/retinoblastoma-a-to-z>) teaches that retinoblastoma cannot be prevented (page 4, last para).
DC Retina (downloaded from URL:<https://dcretina.com/article/stargardt-disease/>) teaches that Stargardt disease cannot be prevented (page 9, 2nd para).
Pediatric Associates of Franklin (downloaded from URL:<https://pediatricassociatesoffranklin.pediatricweb.com/Medical-Content/Medical-Conditions/Hemangioma>) teaches that hemangiomas cannot be prevented (page 2, last para).
(D) The level of one of ordinary skill;
The skill of those skilled in the art is high.
(E) The level of predictability in the art;
Considering that not all eye diseases can be prevented, the unpredictability of preventing each and every eye disease is very high.
(F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The specification does not provide any examples with respect to the use of the claimed compound to treat or prevent any of the claimed eye diseases, other than treatment of retinoblastoma.
The MPEP (2164.02) states that " The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970).” The MPEP further states that
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“Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.”
In the instant application, the specification does not provide any guidance to allow for the prevention of any of the claimed eye diseases or for treatment of each and every eye disease claimed other than retinoblastoma.
Working examples are necessary since the art has indicated unpredictability of treatment of such diseases is very high.
Considering the state of the art as discussed above and the high unpredictability and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to use the invention as claimed.
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 14-16 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 claim 1, the phrases "preferably" and "for example" render the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 1 recites the limitation "the melphalan moiety" in line 22. There is insufficient antecedent basis for this limitation in the claim.
Claim 2 recites the limitation "the “cell-penetrating peptide” moiety" in line 4. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 15, the phrase "particularly" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Furthermore, the claim recites “…layer tissues of eyeball (cornea, sclera, uvea and retina) and appendages of the eyes (lacrimal apparatus, orbital and periorbital structures), including malignant basal cell carcinoma……and also uveitis”. It is unclear whether the layer tissues of eyeball in parenthesis, the appendages of the eyes in parenthesis, and the diseases following the word “including:” are the only layer tissues of eyeball, appendages, and diseases encompassed by the claim (See MPEP § 2173.05(d)). Moreover, “various layer tissues of eyeball” and “appendages of the eyes” are NOT eye diseases. Therefore, the claim is indefinite.
Claims 3-11, 14 and 16, which, directly or indirectly, depend from claim 1 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as these claims incorporate by dependency the indefiniteness of claim 1.
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.
Claims 1-11 and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Wei et al. (WO 2018/224053) in view of Boughton (Intravitreal Chemotherapy for Retinoblastoma: Promising but Controversial; September 1, 2013) and Yang et al. (Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2885).
With respect to claims 1 and 14-16, Wei et al. teach a derivative of the wild type penetrating peptide penetratin, which acts as an ocular absorption enhancer, enables intraocular drug delivery by a non-invasive route, characterized in that the penetratin derivative has the following amino acid sequence:
RX1IKIWFX2X3RRMKWKK
Wherein X1, X2 and X3 represent hydrophobic amino acids selected from the natural sources of amino acids alanine (A), valine (V), leucine (L), isoleucine (Isoleucine, I), proline (P), phenylalanine (F), tryptophan (W), methionine (M) and non-naturally derived amino acids α- A-aminobutyric acid, α-aminopentanoic acid, α-aminohexanoic acid, α-aminoheptanoic acid, and combinations thereof (claim 1), wherein a drug having a diagnostic or therapeutic effect is chemically bonded to form a covalent complex (claim 3).
Wei et al. do not teach that the drug having a therapeutic effect is melphalan.
Boughton teaches treating patients with retinoblastoma by intravitreal injection of melphalan (see Figure on page 1).
Boughton also teaches that “[D]r. Shields said that she has used IVT chemotherapy to treat persistent vitreous seeds and has had remarkable success with a dose of 20 to 30 μg of melphalan. “Intravitreal chemotherapy is exciting and is a real advance in treating vitreous seeds in children with retinoblastoma,” she said. “We have seen no systemic side effects after experiences with 50 injections in children with vitreous seeding from retinoblastoma. In addition, the ocular side effects are minimal, and the retina tolerates the treatment very well.” In a study published in 2012 of 12 patients with vitreous seeding and retinoblastoma, Dr. Shields, in collaboration with researchers in Iran, found that an IVT dose of 10 μg of melphalan achieved control of vitreous seeds in three of seven cases after six months. In four patients who received a 50-μg dose, the tumor control rate was 100 percent, but complications such as cataract, vitreous hemorrhage, and severe hypotony occurred. “With a 20- to 30-μg dose we now achieve good control of the vitreous seeds but with very few complications,” Dr.Shields said” (page 2, last 2 paras).
Yang et al. teach intravitreal administration of melphalan conjugated onto the surface of generation 5 polyamidoamine dendrimer via a pH liable linker for the treatment of retinoblastoma (title; page 2, 2nd para).
It would have been obvious to one of ordinary skill in the art concerned with the treatment of retinoblastoma to use melphalan as the drug having a therapeutic effect of Wei et al. because Boughton teaches successful treatment of retinoblastoma by intravitreal injection of melphalan.
The skilled artisan would have had a reasonable expectation of success because both Wei et al. and Boughton relate to intravitreal administration of the penetratin derivative instantly claimed and melphalan, and further because Yang et al. teach intravitreal administration of a melphalan conjugate.
It is noted that in claim 2, the claimed “cell-cell-penetrating peptide” has been interpreted as “cell-penetrating peptide”.
With respect to claims 2-8, Wei et al. teach that X1, X2 and X3 are tryptophan (W), and the amino acid sequence of the penetratin derivative is:
RWIKIWFQNRRMKWKK
RQIKIWFWNRRMKWKK
RQIKIWFQWRRMKWKK
RWIKIWFWNRRMKWKK
RWIKIWFQWRRMKWKK
RQIKIWFWWRRMKWKK
RWIKIWFWWRRMKWKK (claim 2).
With respect to claims 9-11, Wei et al teach pharmaceutical preparations comprising the conjugate (page 2, 4th para), and further teach intraocular injection. Therefore, the pharmaceutical preparation must necessarily be in liquid form and comprise a pharmaceutically acceptable excipient or carrier.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658
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