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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-9) in the reply filed on 26 May 2026 is acknowledged.
Claims 10-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 26 May 2026.
Information Disclosure Statement
The listing of references in the specification 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.
The information disclosure statements (IDS) submitted on 22 August 2023, 03 April 2025, and 16 January 2023 have been considered by the examiner.
Drawings
The drawings are objected to because they do not comply with 37 CFR 1.84(a)(1), (b)(1) and (l) which requires the use of black ink, that photographs be of sufficient quality so that all details in the photographs are reproducible in the printed patent and solid black lines which are uniformly thick and well-defined. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The disclosure is objected to because of the following informalities: Applicant filed a substitute specification (16 January 2026) in order to correct deficiencies related to Sequence disclosures. However, in the process of amending the specification, the Sequence identifiers which were added on page 2 (lines 24 and 27) are now underlined. This appears to be a mistake as none of the other Sequence identifiers in the specification are underlined.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim recites the abbreviation of Hsp20, however, all abbreviations should be spelled out at their first usage for clarity purposes. 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 1-9 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 1 is directed to a method of treating, reducing the risk of, preventing, or alleviating at least one symptom of a retinal disease, injury or condition in a subject. However, the instant claims are not enabled for preventing or alleviating at least one symptom of any retinal disease, injury or condition. The instant specification fails to teach how administration of a conjugated Hsp20 protein would prevent/alleviate injury to the retina or prevent/alleviate an inherited retinal disease. Furthermore, the claims are not enabled for treating, reducing the risk of, preventing, or alleviating at least one symptom of a retinal disease as broadly claimed as symptoms of retinal disease/injury/condition are not so clearly defined that one of ordinary skill in the art would conclude that Hsp20 would provide relief of any/all symptoms of such. For example, subjects with retinal disease/disorders can suffer from depression because they have loss of vision yet there is no evidence that Hsp20 would be effective for treating depression in said patients although depression is a symptom of the disease/injury/condition. Pain may also be a symptom of retinal injury yet there is no evidence that Hsp20 would provide any relief for pain in a patient with a retinal injury. It is suggested that the claim recite the specific biological effect that is to be achieved by the administration of an Hsp20 protein conjugated to a cell penetrating peptide in a subject with a retinal disease, injury or condition.
From the disclosure of the specification, it would appear that the Hsp20 protein exerts its effects by inhibiting retinal ganglion cell death. However, there is no evidence that Hsp20 can be administered as a prophylactic to prevent retinal injury or to prevent diseases and conditions, especially diseases which are inherited retinal diseases. Further, the instant specification does not enable administration of an Hsp20 protein in a prophylactic manner to reduce the risk of any retinal disease, injury or condition. For one, in most cases, one of ordinary skill in the art would not be apprised of who would be at risk of various retinal conditions or injury. Secondly, there is no evidence of record to suggest that administration of Hsp20 protein would reduce the risk of a retinal disease, injury or condition. Therefore, the instant specification fails to enable such methods, absent evidence to the contrary.
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 1 (and dependent claims 2-9) 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.
Claim 1 recites “at least one symptom of a retinal disease, injury or condition in a subject”. However, the claim is indefinite as it is not clear if the “injury” or “condition” must be of retinal origin or not. Because there are multiple interpretations of the claim, the metes and bounds of the claim are indefinite. Claims 2-9 are indefinite for depending on an indefinite claim as they do not clarify the metes and bounds of what is claimed.
Claim 1 recites “wherein the at least one polypeptide is conjugated with a cell-penetrating peptide”. However, the claim is indefinite as the recitation of “with” does not clearly convey the relationship of the “at least one polypeptide” to the “cell-penetrating peptide”. In other words, it is not clear if the “at least one polypeptide” is conjugated to the “cell penetrating peptide” or if the “at least one polypeptide” is conjugated and the cell-penetrating peptide is administered in addition to the conjugated “at least one polypeptide”.
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.
Claim(s) 1 and 4-9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US PGPub 2015/0133388 A1 (Nagaraj et al.).
Nagaraj et al. teach methods of treating retinal disease, injury or conditions (see [0007], [0053], [0085], [0119]) in a subject by administering intravitreally to an eye of the subject (see [0087]) a therapeutically effective amount of a polypeptide derived from Hsp20 (see [0010], [0011],[0127], and wherein the polypeptide is conjugated with a cell-penetrating peptide (see [0065], [0066], [0068], [0069]). Nagaraj et al. teach a polypeptide that has an amino acid sequence at least 90% identical to SEQ ID NO:3 (see SEQ ID NO:8 and SEQ ID NO:14 of Nagaraj et al.). Nagaraj et al. also teach wherein the retinal disease, injury or condition is glaucoma or diabetic retinopathy (see [0085]) as well as to prevent or reduce damage to retinal and optic nerve tissues (see [0085) and inflammatory conditions (see [0119]). Therefore, Nagaraj et al. anticipates the instant claims.
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.
Claim(s) 1 and 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nagaraj et al. (cited above) in view of either Steinman et al. (US PGPub 2013/0071392 A1) or Nahomi et al. (Biochem. J. 465: 115-125, 2015).
The disclosure of Nagaraj et al. is provided above. Nagaraj et al. does not teach a Hsp20 polypeptide having the amino acid sequence of SEQ ID NO:2.
Steinman et al. teach treating inflammatory diseases by administering small heat shock proteins. Steinman et al. teach a Hsp which has the amino acid sequence of SEQ ID NO:4 (B6; identical to that of the instant SEQ ID NO:2).
Nahomi et al. teach a peptide from Hsp20 which has the amino acid sequence of SEQ ID NO:2. Nahomi et al. also teach that this peptide has robust chaperone and anti-apoptosis activities (see abstract).
It would have been to one of ordinary skill in the art before the effective filing date of the claimed invention to practice the method of Nagaraj et al. using the polypeptide of either Steinman et al. or Nahomi et al. because Steinman et al. teach that B6 is a heat shock protein which has small heat shock protein activity and Nahomi et al. teach that the peptide has robust chaperone and anti-apoptosis activities similar to αB-crystallin and therefore, it would have been obvious to substitute the polypeptide of either Steinman et al. or Nahomi et al. in the method of Nagaraj et al. with the expectation that it would provide the same benefits as the Hsp polypeptides disclosed by Nagaraj et al.
Claim(s) 1 and 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nagaraj et al. (cited above) in view of Gomez et al. (Pharmaceuticals 3: 3594-3613, 2010; doi: 10.3390/ph3123594).
The disclosure of Nagaraj et al. is provided above. Nagaraj et al. does not teach a cell-penetrating peptide that has an amino acid sequence at least 80% identical to SEQ ID NO: 6.
Gomez et al. teach cell penetrating peptides which are 5 amino acids in length, including VPTLK which is identical to that of SEQ ID NO:6 of the instant application (see abstract). Gomez et al. teach that CPP’s are able to penetrate the plasma membrane of living cells and have the ability to carry cargo proteins into the intracellular space (see first paragraph of introduction).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to attach the CPP of Gomez et al. with the amino acid sequence of VPTLK to the Hsp20 protein of Nagaraj et al. for its cell entry properties in order to facilitate entry of the conjugate into the retina. Nagaraj et al. clearly disclose the use of carriers attached to the therapeutic polypeptide (see [0062] and [0065]) to facilitate transport of the therapeutic polypeptides into the cells. One would have a reasonable expectation of success because Gomez et al. teach that CPPs have the known property of being able to penetrate the plasma membrane of living cells. Therefore, the invention as a whole would have been prima facie obvious.
Prior Art of Record
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Nahomi et al. (Biochem. 52(45): 8126-8138, 2013) teach that acetylation of lysine improves the anti-apoptotic activity of human αB-crystallin.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Z Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
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