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 the species SEQ ID NO: 3 in the reply filed on December 18, 2025, is acknowledged. All species, SEQ ID NOs: 1-34, were searched and examined. The election of species requirement mailed October 1, 2025, is withdrawn.
Claim Rejections - 35 USC § 101
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 4, 6, and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more.
Regarding claim 4, BRI of the claim is an isolated peptide that is no more than 10 amino acid residues in length and that comprises the sequence SEQ ID NO: 8-10, 16, 19-24, 26, 27, 30, or 31. The peptide has the function of reducing the amount of dexamethasone-induced spleen and/or thymus weight loss in a mouse. Claim 6 limits the length of the peptide to that of SEQ ID NO: 8-10, 16, 19-24, 26, 27, 30, or 31.
Step 1: Claims 4 and 6 are to a composition of matter.
Step 2A, Prong 1: Claims 4 and 6 are directed to a product of nature, the peptides SEQ ID NO: 8-10, 16, 19-24, 26, 27, 30, and 31. The claimed peptides corresponds to fragments in naturally-occurring proteins as follows:
SEQ ID NO:
Naturally-occurring protein
Corresponds to Residues
Reference
8
DUF4150 domain-containing protein from Pseudomonas saxonica
26-32
Uniprot A0ABY3GCC4
9
Oxidoreductase, molybdopterin-binding subunit from Mycobacterium europaeum
60-66
Uniprot A0A0U1DNJ8
10
Reverse transcriptase zinc-binding domain-containing protein from Tulasnella calospora MUT 4182
16-22
Uniprot A0A0C3QEW1
16
CC2D2AN-C2 domain-containing protein from Haematococcus lacustris
62-68
Uniprot A0A699ZWG8
19
Benzoylsuccinyl-CoA thiolase from Mycolicibacterium setense
74-88
Uniprot A0ABR4YUV7
20
AraC family transcriptional regulator from Streptomyces varsoviensis
5-9
Uniprot A0ABR5J1K1
21
ArsR family transcriptional regulator from Amycolatopsis rifamycinica
7-13
Uniprot A0A066TXG4
22
Histone 3 from Petrolisthes manimaculis
56-62
Uniprot A0AAE1UNY9
23
N-acetyltransferase from Pseudomonas neustonica
8-14
Uniprot A0ABX9XMS2
24
Kelch repeat-containing protein from Trifolium medium
70-76
Uniprot A0A392NYD1
26
DUF4283 domain-containing protein from Solanum pinnatisectum
17-23
Uniprot A0AAV9K823
27
Tubulin/FtsZ GTPase domain-containing protein from Nomascus leucogenys
102-108
Uniprot G1RMJ9
30
DNA (cytosine-5-)-methyltransferase from Pseudomonas vlassakiae
45-49
Uniprot A0A923K362
31
Reverse transcriptase zinc-binding domain-containing protein from
16-22
Uniprot A0A0C3QEW1
The closest counterparts to the nature-based products are the proteins listed in the table above for SEQ ID NOs: 8-10, 16, 19-24, 26, 27, 30, and 31. The claimed peptides have a different structural characteristic than the natural peptide, i.e., the natural peptides have covalent bonds on their ends that connect it to the rest of the protein whereas the claimed peptides lack these bonds. However, the claimed peptides are otherwise structurally identical to the natural peptides, e.g., they had the same peptide backbone and amino acid sequence as SEQ ID NOs: 8-10, 16, 19-24, 26, 27, 30, and 31 in nature. This difference is not a marked difference in view of MPEP § 2106.04(c)(II)(C)(2) and the Supreme Court decision in Myriad. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977. In addition, the function of the claimed peptide, reducing the amount of dexamethasone-induced spleen and/or thymus weight loss in a mouse, is innate to the peptide itself, and was not created or altered by the inventor, including by gathering the peptide in an amount sufficient to carry out the function. See Ambry Genetics, 774 F.3d at 760-61, 113 USPQ2d at 1244. In sum, the claimed peptides are different, but not markedly different, from their naturally occurring counterparts listed in the table above, and thus are natural phenomenon exceptions
Step 2A, Prong 2: The claim only recites the peptide, which is a natural phenomenon exception.
Because the limitation “capable of reducing the amount of dexamethasone-induced spleen and/or thymus weight loss in a mouse” does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration (MPEP § 2106.04(d)(2)).
Step 2B: Because the limitation “capable of reducing the amount of dexamethasone-induced spleen and/or thymus weight loss in a mouse” does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, the claim does not amount to significantly more than the judicial exception (MPEP § 2106.05).
Therefore, claims 4 and 6 are patent ineligible.
Regarding claim 17, BRI of the claim is the peptide in a physiologically acceptable carrier such as water.
Step 1: Claim 17 is to a composition of matter.
Step 2A, Prong 1: Claim 17 is directed to a product of nature, the peptides SEQ ID NOs: 8-10, 16, 19-24, 26, 27, 30, and 31 and the pharmaceutically acceptable carrier, which may be a nature-based product such as water. Because the peptide and water as claimed are not found together in nature, the closest counterparts to the nature-based products are the proteins listed in the table above and water. As determined in the analysis of claims 4 and 6above, the claimed peptides are different, but not markedly different from the proteins listed in the table above. There is no evidence on record that mixing the claimed peptides with water changes the structure, function, or other properties of either the peptides or water in a marked way. Thus, for at least one embodiment of the claim with the BRI (e.g. wherein the carrier is water), the claimed mixture as whole does not display markedly different characteristics compared to the naturally-occurring counterparts. Instead, the peptides and water have the same characteristics in the mixture as the individual components, the same chemical structure and the same function of reducing the amount of dexamethasone-induced spleen and/or thymus weight loss in a mouse and being a solvent. See Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130, 76 USPQ 280, 281 (1948). Accordingly, each component, the peptide and the carrier, is a natural phenomenon exception.
Step 2A, Prong 2: The claim only recites the peptide and the carrier, which are natural phenomenon exceptions. Because there are no additional claim elements besides the judicial exceptions, the judicial exceptions are not integrated into a practical application (MPEP § 2106.04(d)(III)). In addition, because the limitation “capable of reducing the amount of dexamethasone-induced spleen and/or thymus weight loss in a mouse” does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration (MPEP § 2106.04(d)(2)).
Step 2B: Prior to applicant’s invention and at the time of filing the application, using a carrier for a peptide was well-understood, routine, and conventional. Because mixing the peptide with a carrier at this high level of generality does not meaningfully limit the claim, the claim does not amount to significantly more than the judicial exception (MPEP § 2106.05). In addition, because the limitation “capable of reducing the amount of dexamethasone-induced spleen and/or thymus weight loss in a mouse” does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration (MPEP § 2106.04(d)(2)).
Therefore, claim 17 is patent ineligible.
Claim Rejections - 35 USC § 112(a)
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 4-5 and 7-17 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.
BRI of claim 4 is an isolated peptide being no longer than ten amino acids comprising a sequence selected from SEQ ID NOs: 1-34 that is capable of reducing the amount of dexamethasone-induced spleen and/or thymus weight loss in a mouse. SEQ ID NOs: 1-34 range in length from five to seven amino acids meaning that up to three to five amino acids of any identity may be added to the peptides so long as function is preserved and total length is no more than ten. Dependent claims 7-11 require the peptide modifications stapled, cyclized, retro-inversion, addition of a cell penetrating moiety, and addition of a cell penetrating moiety at the N-terminus, respectively. Claim 17 is a pharmaceutical composition comprising a peptide of claim 4.
BRI of claim 12 is a method of treating a disease associated with apoptosis with a peptide of claim 4. The scope of the disease genus includes neurodegenerative diseases (e.g. stroke, Parkinson's, and Alzheimer's disease), myocardial infarction, exposure to radiation or chemotherapeutic agents, inflammation, injuries (e.g., burns and central nervous system injuries), cell aging, hyperthermia, seizures, hypoxias (e.g., ischemia and stroke), autoimmune diseases (e.g. Systemic Lupus Erythematosus disease, Gougerot-Sjogren syndrome, rheumatoid polyarthritis, sarcoidosis, osteopenia, spondyloarthritis, scleroderma, multiple sclerosis, amyotrophic lateral sclerosis, hyperthyroidism, Addison's disease, autoimmune hemolytic anemia, Crohn's disease, Goodpasture's syndrome, Graves' disease, Hashimoto's thyroiditis, idiopathic purpura hemorrhage, insulin-dependent diabetes, myasthenia, pemphigus vulgaris, pernicious anemia, poststreptococcal glomerulonephritis, psoriasis, spontaneous sterility, graft rejections and graft-versus host disease), Alzheimer's disease, Parkinson's disease, secondary degeneration after trauma, glaucoma, macular degeneration, type 1 diabetes, arthritis, systemic inflammatory response syndrome (SIRS), inflammatory bowel disease (IBD), adult respiratory distress syndrome (ARDS), atherosclerosis, hyperthermia, hypoxia, fulminant toxic liver, and kidney failure.
Despite the breadth of the claims, the specification only reduces to practice peptides consisting of SEQ ID NOs: 1-13 in mouse models of dexamethasone-induced spleen and/or thymus weight loss (see Example). Therefore, written description has not been established by actual reduction to practice of a representative number of species of the claimed peptides genus and subgenera of claims 4-5 and 7-17 or the disease scope of claims 12-16.
The specification establishes that there is a high degree of unpredictability associated with the structure-function correlation of the claimed peptides (p. 3, line 31 – p. 4, line 2):
The multi-proline peptide LPPLPYP (SEQ ID NO: 42), also known as IPL344 and Stressin-1) is a short 7 amino acids peptide that protects cells of various types from pro-apoptotic pressures and activates the Akt signaling system. It is a candidate for treating degenerative, inflammatory and autoimmune diseases. Whilst researching the contribution of the individual amino acids of the peptide, the present inventors surprisingly found that particular amino acid replacements of the core sequence showed a significant improvement in reduction of the amount of dexamethasone-induced spleen and/or thymus weight loss in mice, whereas other replacements and/or deletions severely diminished the reduction. In addition, these peptides were shown to minimize the decrease in dexamethasone induced-spleen and thymus cell number.
Despite the large breadth of the claims and the high degree of unpredictability associated with the structure and function of the claimed peptides, the specification has failed to provide guidance on how the addition of up to three to five amino acids will affect the claimed functions of reducing dexamethasone-induced spleen and/or thymus weight and treating diseases associated with apoptosis. Given the sensitivity reported by the specification, one of ordinary skill in the art would not be able to predict which amino acids and how many could be added to the termini of SEQ ID NOs: 1-34 without affecting function. In addition, given the sensitivity reported by the specification, one of ordinary skill in the art would not be able to predict how modifying SEQ ID NOs: 1-34 by stapling, cyclization, retro-inversion, or the addition of a cell penetrating moiety would affect function. Regarding claims 12-16, the specification does not establish how the animal model in the example correlates to any, let alone the full scope of the diseases claimed.
For these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Claims 4-5 and 7-17 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 treating ALS with a peptide consisting of SEQ ID NOs: 1-33 or 34, does not reasonably provide enablement for treating ALS with a peptide comprising a peptide of SEQ ID NOs: 1-33 or 34 or derivative thereof, or for using any claimed peptide in a method of treating any other disease. 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.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors 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. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention
The invention is in the field of therapeutic peptides.
The breadth of the claims
BRI of claim 4 is an isolated peptide being no longer than 10 amino acids comprising a sequence selected from SEQ ID NOs: 1-34 that is capable of reducing the amount of dexamethasone-induced spleen and/or thymus weight loss in a mouse. SEQ ID NOs: 1-34 range in length from five to seven amino acids meaning that up to three to five amino acids of any identity may be added to the peptides so long as function is preserved and total length is no more than ten. Dependent claims 7-11 require the peptide modifications stapled, cyclized, retro-inversion, addition of a cell penetrating moiety, and addition of a cell penetrating moiety at the N-terminus, respectively. Claim 17 is a pharmaceutical composition comprising a peptide of claim 4.
BRI of claim 12 is a method of treating a disease associated with apoptosis with a peptide of claim 4. The scope of the disease genus includes neurodegenerative diseases (e.g. stroke, Parkinson's, and Alzheimer's disease), myocardial infarction, exposure to radiation or chemotherapeutic agents, inflammation, injuries (e.g., burns and central nervous system injuries), cell aging, hyperthermia, seizures, hypoxias (e.g., ischemia and stroke), autoimmune diseases (e.g. Systemic Lupus Erythematosus disease, Gougerot-Sjogren syndrome, rheumatoid polyarthritis, sarcoidosis, osteopenia, spondyloarthritis, scleroderma, multiple sclerosis, amyotrophic lateral sclerosis, hyperthyroidism, Addison's disease, autoimmune hemolytic anemia, Crohn's disease, Goodpasture's syndrome, Graves' disease, Hashimoto's thyroiditis, idiopathic purpura hemorrhage, insulin-dependent diabetes, myasthenia, pemphigus vulgaris, pernicious anemia, poststreptococcal glomerulonephritis, psoriasis, spontaneous sterility, graft rejections and graft-versus host disease), Alzheimer's disease, Parkinson's disease, secondary degeneration after trauma, glaucoma, macular degeneration, type 1 diabetes, arthritis, systemic inflammatory response syndrome (SIRS), inflammatory bowel disease (IBD), adult respiratory distress syndrome (ARDS), atherosclerosis, hyperthermia, hypoxia, fulminant toxic liver, and kidney failure.
The State of the Prior Art
Ovadia et al. teach methods for treating ALS comprising administering a composition comprising the peptide stressin-1 LPPLPYP (SEQ ID NO: 1) (para. [0024]). SEQ ID NOs: 1-34 are each analogs or derivatives of stressin-1.
The Predictability or Unpredictability of the Art
The specification establishes that there is a high degree of unpredictability associated with the structure-function correlation of the claimed peptides (p. 3, line 31 – p. 4, line 2):
The multi-proline peptide LPPLPYP (SEQ ID NO: 42), also known as IPL344 and Stressin-1) is a short 7 amino acids peptide that protects cells of various types from pro-apoptotic pressures and activates the Akt signaling system. It is a candidate for treating degenerative, inflammatory and autoimmune diseases. Whilst researching the contribution of the individual amino acids of the peptide, the present inventors surprisingly found that particular amino acid replacements of the core sequence showed a significant improvement in reduction of the amount of dexamethasone-induced spleen and/or thymus weight loss in mice, whereas other replacements and/or deletions severely diminished the reduction. In addition, these peptides were shown to minimize the decrease in dexamethasone induced-spleen and thymus cell number.
The Level of Guidance in the Specification
Despite the large breadth of the claims and the high degree of unpredictability associated with the structure and function of the claimed peptides, the specification has failed to provide guidance on how the addition of up to three to five amino acids will affect the claimed functions of reducing dexamethasone-induced spleen and/or thymus weight and treating diseases associated with apoptosis. Given the sensitivity reported by the specification, one of ordinary skill in the art would not be able to predict which amino acids and how many could be added to the termini of SEQ ID NOs: 1-34 without affecting function. In addition, given the sensitivity reported by the specification, one of ordinary skill in the art would not be able to predict how modifying SEQ ID NOs: 1-34 by stapling, cyclization, retro-inversion, or the addition of a cell penetrating moiety would affect function. Regarding claims 12-16, the specification does not establish how the animal model in the example correlates to any, let alone the full scope of the diseases claimed.
The Presence or Absence of Working Examples
Despite the breadth of the claims, the specification only reduces to practice peptides consisting of SEQ ID NOs: 1-13 in mouse models of dexamethasone-induced spleen and/or thymus weight loss (see Example).
The Quantity of Experimentation Necessary
Considering the factors above, the skilled artisan would be burdened with undue experimentation in determining if one of the claimed peptides would be effective at reducing the amount of dexamethasone-induced spleen and/or thymus weight loss and/or treating neurodegenerative diseases (e.g. stroke, Parkinson's, and Alzheimer's disease), myocardial infarction, exposure to radiation or chemotherapeutic agents, inflammation, injuries (e.g., burns and central nervous system injuries), cell aging, hyperthermia, seizures, hypoxias (e.g., ischemia and stroke), autoimmune diseases (e.g. Systemic Lupus Erythematosus disease, Gougerot-Sjogren syndrome, rheumatoid polyarthritis, sarcoidosis, osteopenia, spondyloarthritis, scleroderma, multiple sclerosis, amyotrophic lateral sclerosis, hyperthyroidism, Addison's disease, autoimmune hemolytic anemia, Crohn's disease, Goodpasture's syndrome, Graves' disease, Hashimoto's thyroiditis, idiopathic purpura hemorrhage, insulin-dependent diabetes, myasthenia, pemphigus vulgaris, pernicious anemia, poststreptococcal glomerulonephritis, psoriasis, spontaneous sterility, graft rejections and graft-versus host disease), Alzheimer's disease, Parkinson's disease, secondary degeneration after trauma, glaucoma, macular degeneration, type 1 diabetes, arthritis, systemic inflammatory response syndrome (SIRS), inflammatory bowel disease (IBD), adult respiratory distress syndrome (ARDS), atherosclerosis, hyperthermia, hypoxia, fulminant toxic liver, and kidney failure. The skilled artisan would be burdened with testing a broad range of peptides in in vitro assays correlated to the claimed diseases. The active inhibitors would then have to be subjected to animal models of the claimed diseases. The experimentation required represents years of inventive effort. When the above factors are weighed, it is the examiner's position that one skilled in the art could not practice the invention without undue experimentation.
Therefore, in view of the Wands factors, the claims appear to require undue experimentation to use the full scope of the claimed invention.
Claim Rejections - 35 USC § 112(b)
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 4 and 6-17 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 4 recites SEQ ID NOs: 7 and 13. SEQ ID NO: 7 is LPPLPYP wherein position 2 is dimethylproline. SEQ ID NO: 13 is LPPLPYP wherein position 3 is dimethylproline. The claim is indefinite because the structure of dimethylproline is undefined. It is not clear from the specification, sequence listing, or claims whether dimethylproline is e.g. N,N-dimethylproline, 1,2-dimethylproline, 3,3-dimethylproline, 5,5-dimethylproline, etc. As a result, the structure of SEQ ID NOs: 7 and 13 is undefined.
Dependent claims 6-17 fail to remedy this issue and are likewise rejected.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 9 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 9 depends from claim 4 and requires that the order of the sequence is reversed and all of the amino acids are of the D-type. Because claim 4 is limited to a peptide of no more than 10 amino acid residues in length comprising one of SEQ ID NOs: 1-34 and because SEQ ID NOs: 1-34 are fully defined amino acid sequences, a requirement to reverse the sequence and change all amino acids to D-amino acids fails to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
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 4 and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gyuris et al. (US 2003/0166004 A1).
Gyuris et al. teaches the isolated peptide AWWWNPPLAY (SEQ ID NO: 130), which is no longer than 10 amino acids in length and which comprises instant SEQ ID NO: 20 (underlined) (see Figure 1, second page, column 2). The peptide satisfies all of the structural limitations of claim 4.
Regarding the limitation “capable of reducing dexamethasone-induced spleen and/or thymus weight loss in a mouse,” a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, because the prior art peptide meets all of the structural limitations of the claim, it must be capable of the claimed intended use.
Regarding claim 17, Gyuris et al. teach that the peptide can be combined with a pharmaceutically acceptable carrier (abstract, para. [0113], claims 3 and 28).
Claims 4 and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Staecker et al. (US 2013/0096070 A1).
Staecker et al. teaches the isolated peptide QPPHPYR (SEQ ID NO: 43), which is less than 10 amino acids in length and which comprises instant SEQ ID NO: 30 (underlined) (see Table 1, second page). The peptide satisfies all of the structural limitations of claim 4.
Regarding the limitation “capable of reducing dexamethasone-induced spleen and/or thymus weight loss in a mouse,” a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, because the prior art peptide meets all of the structural limitations of the claim, it must be capable of the claimed intended use.
Regarding claim 17, Staecker et al. teach that the peptide can be combined with a pharmaceutically acceptable carrier (para. [0014], [0026], [0040]).
Claim 9 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ovadia et al. (US 2014/0088017 A1).
Ovadia et al. teach the peptide PYPLPPL (SEQ ID NO: 2), wherein all residues are in the "D" isomeric form (para. [0004]). This peptide is a peptide identical to instant SEQ ID NO: 6, 17, and 34 wherein the order of the sequence is reversed and all of the amino acids are of the D-type.
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 for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 4, 6, 12-15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Ovadia et al. (US 2014/0088017 A1).
Determining the scope and contents of the prior art.
Ovadia et al. teach methods for treating neurodegenerative diseases such as ALS comprising administering a composition comprising the peptide LPPLPYP (SEQ ID NO: 1), the retro-inverso peptide PYPLPPL (SEQ ID NO: 2), wherein all amino acids are in D-form, or analogs or derivatives thereof (para. [0024]).
Ascertaining the differences between the prior art and the claims at issue.
The peptide LPPLPYP of Ovadia et al. shares the same amino acid sequence as instant SEQ ID NOs: 6, 17, 18, and 34 with one difference in each:
Instant SEQ ID NO: 6 contains a single D-amino acid at position 4 (D-Leu) whereas the prior art peptide contains L-amino acids at all positions;
Instant SEQ ID NO: 17 contains a single D-amino acid at position 7 (D-Pro) whereas the prior art peptide contains L-amino acids at all positions;
Instant SEQ ID NO: 18 is acetylated at the N-terminus whereas the prior art peptide contains an unmodified N-terminus; and
Instant SEQ ID NO: 34 contains a single D-amino acid at position 3 (D-Pro) whereas the prior art peptide contains L-amino acids at all positions;
Resolving the level of ordinary skill in the pertinent art.
Regarding instant SEQ ID NOs: 6, 17, and 34, Ovadia et al. teach that D-amino acids can be introduced to a peptide sequence to reduce the susceptibility of mimics to cleavage and inactivation by peptidases (para. [0100]).
Regarding instant SEQ ID NO: 18, Ovadia et al. teach that a peptide derivative may contain N-terminal aceytlation (para. [0093]).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The specification does not present evidence that SEQ ID NOs. 6, 17, 18, and 34 possess unexpected beneficial properties relative to the peptides in Ovadia et al.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the peptide LPPLPYP by introducing a D-amino acid or N-terminal acetylation as taught by Ovadia et al. The rationale for obviousness is "obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success (MPEP § 2143.01(E)). The relevant findings for this rationale are as follows.
(1) At the relevant time, there had been a recognized problem or need in the art, which may include a design need or market pressure to solve a problem. In the instant case, Ovadia et al. teaches that the peptide LPPLPYP is useful for the treatment of neurodegenerative disease such as ALS (para. [0024]) but like other peptide drugs may be vulnerable to degradation by peptides (para. [0100]). Therefore, there had been a recognized problem or need in the art, which may include a design need or market pressure to solve a problem.
(2) There had been a finite number of identified, predictable potential solutions to the recognized need or problem. Ovadia et al. teach that D-amino acids can be introduced to a peptide sequence to reduce the susceptibility of mimics to cleavage and inactivation by peptidases (para. [0100]). Substituting each of the amino acids in LPPLPYP with its corresponding D-amino acid would yield seven different peptides, including those identical to instant SEQ ID NOs: 6, 17, and 34. Acetylating the N-terminus would yield one peptide, identical to instant SEQ ID NO: 18. The number of peptides produced by this modification, eight, is comparable to the number the courts held as a finite in Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 82 USPQ2d 1321 (Fed. Cir. 2007) (the court rejected the notion that unpredictability could be equated with nonobviousness here, because there were only a finite number (53) of pharmaceutically acceptable salts to be tested for improved properties). Therefore, there had been a finite number of identified, predictable potential solutions to the recognized need or problem.
(3) One of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success. One of ordinary skill in the art would expect that the derivatives of LPPLPYP containing D-amino acids would maintain the function of treating ALS because Ovadia et al. teach that an all D-amino acid, retro-inverso peptide, SEQ ID NO: 2, is also active. Therefore, one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
(4) Whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness. The specification does not present evidence that SEQ ID NOs. 6, 17, 18, and 34 possess unexpected beneficial properties relative to the peptides in Ovadia et al.
The rationale to support a conclusion that the claim would have been obvious is that "a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103."KSR, 550 U.S. at 421, 82 USPQ2d at 1397.
Therefore, claims 4 and 6 are obvious over the cited art.
Regarding claims 12-15, Ovadia et al. teach that the peptides can be used to treat neurodegenerative diseases including ALS, which is also an autoimmune disease1 (para. [0024]).
Regarding claim 17, Ovadia et al. teach that the peptides can be combined with a pharmaceutically acceptable excipient, carrier or diluent (para. [0052]).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 4 and 12-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,912,790. Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate the instant claims.
Patented claim 1 recites an isolated peptide consisting of the amino acid sequence as set forth in SEQ ID NO: 21, wherein the amino acid at position 1 is a D-amino acid, wherein the peptide is capable of reducing the amount of dexamethasone-induced spleen and/or thymus weight loss in a mouse. The peptide is D-Leu Pro Pro Leu Ala Tyr Pro, which is less than 10 amino acids in length and which comprises instant SEQ ID NO: 20 (underlined). Therefore, patented claim 1 anticipates instant claim 4.
Regarding claims 12-16, a claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use (Sun Pharmaceutical. Industries, Ltd. v. Eli Lilly & Co., 611 F.3d 1381 (Fed. Cir. 2010)). In the instant case, U.S. Patent No. 11,912,790 discloses using the peptide recited in patented claim 1 for methods of treating diseases associated with apoptosis including inflammatory, degenerative, autoimmune, and neurodegenerative diseases such as ALS, AMD, stroke and myocardial infarction (col 17-18).
Regarding claim 17, patented claim 2 recites a pharmaceutical composition comprising the isolated peptide of claim 1.
Claims 4, 12-15 and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 12 of copending Application No. 18/586,715 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims anticipate the instant claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claim 1 recites an isolated peptide being no longer than ten amino acids which comprises an amino acid sequence as set forth in SEQ ID NOs: 3, 4, 7, 18 or 20, wherein the peptide is capable of reducing the amount of dexamethasone-induced spleen and/or thymus weight loss in a mouse. Reference claim SEQ ID NO: 4 is LPPLAYP, which is less than 10 amino acids in length and which comprises instant SEQ ID NO: 20 (underlined). Reference claim SEQ ID NO: 18 is PPLAYP, which is less than 10 amino acids in length and which comprises instant SEQ ID NO: 20 (underlined). Therefore, reference claim 1 anticipates instant claim 4.
Regarding claims 12-15, reference claim 1 recites a method of treating ALS with SEQ ID NOs: 3, 4, 7, 18 or 20.
Regarding claim 17, reference claim 12 recites a pharmaceutical composition comprising the isolated peptide of claim 1.
Allowable Subject Matter
The following claims drafted by the examiner and considered to distinguish patentably over the art of record in this application, are presented to applicant for consideration:
4. An isolated peptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-5, 11-12, 14-15, 25, 28-29, 32, and 33.
5. The isolated peptide of claim 4 consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-5.
Cancel claims 6-11.
12. A method of treating amyotrophic lateral sclerosis (ALS) comprising administering a therapeutically effective amount of the isolated peptide of claim 4 to a subject in need thereof, thereby treating the ALS.
Cancel claims 13-16.
17. A pharmaceutical composition comprising an isolated peptide of claim 4 and a pharmaceutically acceptable carrier.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 7 am - 3 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
1 Michaelis et al. (Autoimmune response to C9orf72 protein in amyotrophic lateral sclerosis. Nature 647, 970–978 (2025)) is cited as evidence that ALS is an autoimmune disease. A reference showing a inherency does not have to be prior art. See MPEP § 2112(II).