DETAILED ACTION
Examiner acknowledges receipt of the reply filed 4/20/2026, in response to the restriction requirement mailed 2/19/2026.
Claims 1-22 and 29 are pending and being examined on the merits in this office 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 .
Priority
The filing receipt dated 05/22/2024 provides the following information:
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Election/Restrictions
Applicant’s election of the following representative species is acknowledged:
Compound: LTX-9
causative/infectious agent: virus
disease: pneumonia
Claims 1-16, 18-22, and 29 read on the elected species.
Upon searching the elected species of virus, an additional species was found e.g. bacteria. Accordingly, for purposes of compact prosecution, the election of species of is modified only to the extent of examining this additional species. Otherwise the election of species requirement is still retained.
Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc.
Claim Objections
Claims 1, 2, 8, 12, 20, and 29 are objected to because of the following informalities:
Claim 1 should be amended to recite “method for [[the]] treatment of sinusitis”.
Regarding claim 2, line 2 should be moved up one line for continuous text on line 2.
Claim 8 should be amended to recite “-Ra-[[ ]]Rb-“ to remove the extra space.
Claim 15 should be amended to recite “compound comprises
Claim 20 should be amended to recite “comprising a diluent, carrier, , or a combination thereof”.
Claim 29 should be amended to recite “pneumonia, , or a combination thereof”.
Appropriate correction is required.
Examiner recommends that claim 4 be amended to depend from claim 3, instead of claim 1, because claim 4 narrows the limitations of claim 3.
Examiner recommends that claim 13 be amended to depend from claim 12, instead of claim 1, because claim 13 narrows the limitations of claim 12.
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 11, 15, and 18 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 11 recites the limitation "the R group" at line 6. There is insufficient antecedent basis for this limitation in the claim. To overcome this rejection, claim 11 should be amended to recite "the lipophilic R group".
Claim 15 recites the limitation "the structural formula". There is insufficient antecedent basis for this limitation in the claim. To overcome this rejection, examiner recommends that claim 15 be amended to recite "compound comprises
Claim 18 recites the limitation "the first administration". There is insufficient antecedent basis for this limitation in the claim.
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 1-22 and 29 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 for treatment of sinusitis, pneumonia or otitis caused by an infectious agent in a subject in need thereof by administering an effective amount of LTX-109, LTX-7, or LTX-12, does not reasonably provide enablement for a method for the prevention/prophylaxis of sinusitis, pneumonia or otitis comprising administering an effective amount of a compound of formula (I). 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 use the invention commensurate in scope with these claims.
“[T]o 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.’” Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (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. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
Breadth of the Claims
The claims are drawn to a method for the treatment of sinusitis, pneumonia or otitis in a subject in need thereof, wherein said method comprises administering to said subject an effective amount of a compound of formula (I) AA-AA-AA-X-Y-Z (I). Formula (I) is defined in a generic sense as three amino acids, where two in any order are cationic in nature and the third is one with a lipophilic side chain of 14-27 non-hydrogen atoms, where the tripeptide is also attached to a N atom optionally substituted by a branched or unbranched C1-C10 alkyl or aryl group that may incorporate up to two N, O, or S atoms, a group RaRb, RaRbRb or RbRbRa where Ra is C, O, S, or N and where Rb is C, and where both Ra and Rb may be substituted with C1-C4 alkyl groups, and a final group comprising 1-3 cyclic groups each of 5 or 6 non-hydrogen atoms with two or more of the cyclic groups optionally fused and one may optionally be substituted and be up to 15 non-hydrogen atoms. The compound as claimed offers a broad number of possible species given the variable positions throughout.
The specification states at p. 20:
The term "treatment" or "therapy" used herein includes therapeutic and preventative (or prophylactic) therapies. Thus, compounds for use in accordance with the invention may be for therapeutic or prophylactic uses. "Treatment" or "therapy" includes administration of a compound in accordance with the invention to subjects having, or suspected of having, sinusitis, pneumonia or otitis.
Accordingly, the instant claim scope includes numerous peptides, as well as treating and preventing sinusitis, pneumonia or otitis from any source, including but not limited to, bacterial and viral sources/causative agents.
The nature of the invention and predictability/unpredictability in the art
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
It is noted that pharmaceutical and biological art is generally unpredictable, requiring each embodiment to be individually assessed for physiological activity. Given this fact, historically the development of new drugs has been difficult and time-consuming. There is no absolute predictability, even in view of the high level of skill in the art.
State of the Prior Art
The prior art recognizes the potential usage of LTX-109 in treatment of certain bacterial infections through disruption of the bacterial cell membrane. See e.g. Nilsson et al. (Antimicrobial Agents and Chemotherapy 59:145-151, published 2015- cited in IDS filed 8/17/2023).
Intervening art suggests that peptides might be developed to disrupt viral envelopes. See e.g. Jackman (J Biochimica et Biophysica Acta – Biomembranes 1864:183821 (Nov 2021)). However, there is no suggestion from Jackman or other prior art references to prepare LTX-109, LTX-7, or LTX-12 and utilize them as treatments for sinusitis, pneumonia or otitis.
LTX-109 and variants have been suggested as useful as antifungals against Saccharomyce cerevisiase and Zygosaccharomyces bailii. See e.g. Larsen et al. (FEMS Yeast Research 15:fov011 (2015)).
Relative Skill of those in the Art
MPEP 2141.03 states (in part)” A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) (disagreeing with the examiner’s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering). In the instant case, the skill in the art high with respect to physicians and scientists. The level of skill in the art (physicians and scientists) would be high.
Amount of Direction or Guidance Given
The specification discloses that tripeptides with C-terminal modifications exhibit antiviral activity towards enveloped viruses, noting that they are cationic and bulky, and noting LTX-109 as one such compound (see e.g. p.1-2). The specification notes that antiviral activity of these compounds has not been previously recognized (see e.g. p.2). Four compounds are disclosed: LTX-109, Arg-Phe(4-(1-Naphthyl))-Arg-NH-CH2-CH2-Ph, LTX-7, and LTX-12 (see e.g. p.4-6). Assessment of the antiviral activity is described through use of TCID50 assays as well as microscopy (see e.g. p.9). The compounds may exert a direct membrane-affecting mechanism (see e.g. p.9).
Presence/Absence of Working Examples
Example 1 shows that 1% LTX-109 serves to reduce infection of influenza A virus infection in vitro. Example 2 shows that 1% LTX-109 serves to reduce infection of respiratory syncytial virus infection in vitro. Example 3 shows that 1% LTX-109 serves to reduce infection of SARS-CoV-2 infection in vitro. Example 4 shows that LTX-109 has antibacterial [against Gram positive and Gram negative bacteria] and antifungal activity (Table 4). Example 5 shows antibacterial activity against M pneumoniae bacterium in vitro. Examples 6-7 show that LTX-109 (at 1% or 3%) reduces Rhinovirus infection in vitro. Example 8 shows that LTX-12 reduces SARS-CoV-2 infection in vitro. Example 9 shows that LTX-7 reduces influenza A infection in vitro. Example 10 shows that LTX-7 reduces Rhinovirus infection in vitro. Example 11 shows that LTX-7 has antibacterial [against Gram positive and Gram negative bacteria] and antifungal activity (Table 10).
Thus, the specification reduced to practice 3 peptides that fall within the scope of the claimed formula I. No examples of preventing or prophylaxis were reduced to practice.
Quantity of Experimentation Necessary
Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: "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. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention." Applicant cannot rely on the knowledge of one skilled in the art to supply information on the novel aspects of the claimed invention. Thus, in view of the reasons set forth above, it would take an undue amount of experimentation for one of skill in the art to practice the claimed invention.
The claims reflect a variety of tripeptide derivatives that target entire classes of infections (bacterial, viral, etc.). The skilled artisan is left with both a broad genus of compounds as well as a broad genus of conditions to treat. In this case, limited guidance on specific compounds is provided, and only three compounds are tested against highly limited examples. There is no guidance as to prevention/prophylaxis of any infection comprising the claimed compounds, much less amounts/dosing regimen required for prevention/prophylaxis. The collective effort required to make and use the invention poses and undue burden on the part of the skilled artisan given the above factors.
Owing the factors listed above, the amount of experimentation needed will be extensive in view of the lack of guidance by the inventor. MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” Because of the scope of the claim language, one of ordinary skill in the art would be burdened with undue “painstaking experimentation study” to practice 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.
The factual inquiries 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 1-22 and 29 is/are rejected under 35 U.S.C. 103 as being obvious over Lükten et al. (U.S. 2024/0156893, PGPUB of copending Appl. No. 18/546794), and further in view of Ruuskanen et al (Lancet 377:1264-1275 (2011)).
The applied reference has a common applicant and inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). The earliest effective filing date of the ‘794 application is 03/19/2021, the filing date of priority application GB 2103872.4.
Lükten et al. teach treatment of an enveloped virus infection in a subject, wherein said compound is a compound of Formula (I) as defined herein: AA-AA-AA-X-Y-Z (I) wherein, in any order, 2 of said AA (amino acid) moieties are cationic amino acids and 1 of said AA is an amino acid with a lipophilic R group, the R group having 14-27 non-hydrogen atoms; X is a N atom, which may be substituted by a branched or unbranched C1-C10 alkyl or aryl group which group may incorporate up to 2 heteroatoms selected from N, O and S; Y represents a group selected from —Ra—Rb—, —Ra—Rb—Rb— and —Rb—Rb—Ra— wherein Ra is C, O, S or N, and Rb is C; each of Ra and Rb may be substituted by C1-C4 alkyl groups or unsubstituted; and Z is a group comprising 1 to 3 cyclic groups each of 5 or 6 non-hydrogen atoms, 2 or more of the cyclic groups may be fused and one or more of the cyclic groups may be substituted; the Z moiety incorporates a maximum of 15 non-hydrogen atoms; and wherein the bond between Y and Z is a covalent bond between Ra or Rb of Y and a non-hydrogen atom of one of the cyclic groups of Z (claim 1). Viruses include a Coronavirus, an Orthopneumovirus or an Orthomyxovirus (claim 18). The virus is SARS-CoV-2, Respiratory Syncytial Virus (RSV) or Influenza A virus (claim 19). The virus can cause a respiratory infection, including an upper respiratory tract infection (e.g., pars [0059]-[0073], claims 17-18).
Although Lükten et al. teach treatment of a respiratory tract infection caused by a virus, the reference does not explicitly teach that the respiratory tract infection in pneumonia.
Ruuskanen et al teach that pneumonia is a common illness that continues to be the major killer of young children in developing countries and elderly people in developed countries. Many microorganisms are associated with pneumonia, and now attention is turning to the importance of viruses as pathogens. The emergence of severe acute respiratory syndrome (SARS), avian influenza A (H5N1) virus, and the 2009 pandemic influenza A (H1N1) virus has re-emphasized the important role of respiratory viruses as causes of severe pneumonia (p. 1264). The panel at p. 1265 provides a list of viruses community-acquired pneumonia in children and adults, including Influenza A, Coronaviruses, Respiratory syncytial viruses.
It would have been obvious to one of ordinary skill in the art to administer a peptide of formula I to a patient with viral pneumonia, e.g., caused by SARS or influenza A, in order to treat the pneumonia. The skilled artisan would have recognized from Lükten et al. that the peptides can be used to treat respiratory tract infection caused by viruses. Ruuskanen et al explicitly taught viruses e.g. Influenza A, Coronaviruses, Respiratory syncytial viruses are causative agents of viral pneumonia. The skilled artisan would have had a reasonable expectation of success because this was the specific patient population (e.g., a subject with a respiratory tract infection caused by a virus, e.g., influenza A or a coronavirus). Lükten et al. sought to treat with the instantly claimed peptides of formula I.
Accordingly, instant claims 1, 16, and 29 are rendered obvious.
Regarding claim 2, Lükten teaches that the compound is a peptide or a peptidomimetic (e.g., paras. [0016], [0035]-[0041]). Regarding claims 3 and 4, the cationic amino acids are lysine and/or arginine (e.g., paras [0006], [0014], claims 3-4). Regarding claim 5, Lükten teaches that the lipophilic R group contains 2 or more of cyclic groups optionally fused or connected (e.g., paras [0006]-[0013], claims 1 and 5). Regarding claim 6, X may be unsubstituted (e.g., paras [0006]-[0013], claims 1 and 6). Regarding claim 7, Ra is C (e.g., paras [0006]-[0013], claims 1 and 7). Regarding claims 8 and 9, Y is -Ra-Rb- and unsubstituted, e.g., -CH2-CH2- (paras [0025], [0032], claims 1 and 9). Regarding claim 10, Z is phenyl (e.g., paras [00 06]-[0013], [0026], [0027], claim 10). Regarding claim 11, Lükten teaches that the compound can of formula II wherein AA1 is a cationic amino acid, preferably lysine or arginine but may be histidine or any non-genetically coded or modified amino acid carrying a positive charge at pH 7.0; AA2 is an amino acid with a large lipophilic R group, the R group having 14-27 non-hydrogen atoms and preferably containing 2 or more, e.g. 2 or 3, cyclic groups which may be fused or connected, these cyclic groups will typically comprise 5 or 6 non-hydrogen atoms, preferably 6 non-hydrogen atoms; and X, Y and Z (e.g., para [0017], [0006]-[0013], claim 11). Regarding claims 12 and 13, the lipophilic R group is selected from the group consisting of tributyl tryptophan (Tbt) or a biphenylalanine derivative such as Phe(4-(2-Naphthyl)), Phe(4-(1-Naphthyl)), Bip (4-n-Bu), Bip (4-Ph) or Bip (4-T-Bu); Phe(4-(2-Naphthyl) (e.g., paras [0024], [0033], claims 12-13). Regarding claim 14, X-Y-Z us -NHCH2CH2Ph (e.g., paras [0027], [0030]-[0033], claim 14). Regarding claim 15, Lükten discloses the same structural formula, e.g. claim 15. Regarding claim 16, the causative agent can be a virus (e.g., paras [0062]-[0072], claims 1, 16-18, and 24). Regarding claims 17 and 18, Lükten teaches that the compound can be used to treat viral or bacterial pathogens (LTX109 has antibacterial activity) (paras [0005], [0062]-[0072]). Regarding claim 19, the subject is a human subject (e.g., paras. [0058], [0097], claims 20, 26, 29). Regarding claim 20, the compound is in a pharmaceutical formulation further comprising a diluent, carrier, and/or an excipient (e.g., paras [0074]-[0084], claim 21). Regarding claim 21, the treatment is a therapeutic treatment (e.g., paras [0003], [0087]-[0091], claim 22). Regarding claim 22, the treatment is a prophylactic treatment (e.g., paras [0003], [0087]-[0091], claim 23).
Accordingly, claims 1-16, 18-22, and 29 are rendered obvious in view the teachings of the cited references.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Claim(s) 1-22 and 29 is/are rejected under 35 U.S.C. 103 as being unpatentable Stensen et al (U.S. 20110172145), and further in view of Cillóniz et al (Ann Res Hosp 2:1 (2018)).
Stensen et al teach a compound of formula (I) AA-AA-AA-X—Y—Z wherein, in any order, 2 of said AA (amino acid) moieties are cationic amino acids and 1 of said AA is an amino acid with a lipophilic R group, the R group having 14-27 non-hydrogen atoms; X is a N atom, which may be substituted by a branched or unbranched C1-C10 alkyl or aryl group which group may incorporate up to 2 heteroatoms selected from N, O and S; Y represents a group selected from —Ra—Rb—, —Ra—Rb—Rb— and —Rb—Rb—Ra— wherein Ra is C, O, S or N, and Rb is C; each of Ra and Rb may be substituted by C1-C4 alkyl groups or unsubstituted; and Z is a group comprising 1 to 3 cyclic groups each of 5 or 6 non-hydrogen atoms, 2 or more of the cyclic groups may be fused and one or more of the cyclic groups may be substituted; the Z moiety incorporates a maximum of 15 non-hydrogen atoms; and wherein the bond between Y and Z is a covalent bond between Ra or Rb of Y and a non-hydrogen atom of one of the cyclic groups of (abstract, claim 1). The compounds have utility as antimicrobial or antitumoral agents (e.g., abstract, paras. [0028]-[0030], [0039], [0051]-[0055], claim 15). Table 1 discloses that peptides of instant formula I that had antibacterial and antifungal activity against Gram-positive bacteria, Gram-negative bacteria and fungi (Ex 1).
Although Stensen et al. teach treatment of a bacterial infection comprising the claimed peptide compounds, the reference does not explicitly teach that the infection is pneumonia.
Cillóniz et al teach that Streptococcus pneumoniae is the most frequent causative pathogen of community acquired pneumonia (CAP) (e.g., p. 1). Other bacterial causative agents of pneumonia include Legionella, Mycoplasma, Moraxella spp, Haemophilus influenzae, and Staphylococcus aureus (e.g., table 1, p. 3 and 8).
It would have been obvious to one of ordinary skill in the art to administer a peptide of formula I to a patient with bacterial pneumonia, e.g., caused by Streptococcus pneumoniae, in order to treat the pneumonia. The skilled artisan would have recognized from Stensen et al. that the peptides can be used to treat bacterial infections. Cillóniz et al explicitly taught Streptococcus pneumoniae is the most common cause of bacterial pneumonia. The skilled artisan would have had a reasonable expectation of success in treating bacterial pneumonia caused by Streptococcus pneumoniae because this was the specific patient population (e.g., a subject with a bacterial infection) that Stensen et al. sought to treat with the instantly claimed peptides of formula I. Stensen et al further taught that the claimed peptides had antibacterial activity against Streptococcus pneumoniae (e.g., Table 1). See also antibacterial activity against the bacterium Haemophilus influenzae and Staphylococcal aureus- other known causative agents of pneumonia.
Accordingly, instant claims 1, 16, and 29 are rendered obvious.
Regarding claim 2, the compound is a peptide or a peptidomimetic (e.g., paras [0033]-[0038], [0051], claim 2). Regarding claims 3 and 4, the cationic amino acids are lysine and/or arginine (e.g., paras [0008], [0019], claim 3). Regarding claim 5, the lipophilic R group contains 2 or more cyclic groups (e.g., abstract, paras [0008]-[0013], [0020], [0027], claims 1, 4, 13). Regarding claim 6, X is unsubstituted (e.g., claim 5). Regarding claim 7, Ra is C (e.g., abstract, para [0011], claims 1, 6). Regarding claims 8 and 9, Y is -Ra-Rb- and unsubstituted (e.g., abstract, paras [0010], Ex 1-3, claims 7-8, 12). Regarding claim 10, X is phenyl (examples 1-3, claims 9, 12, 13). Regarding claim 11, the compound is a compound of formula II formula (II) AA1-AA2-AA1-X—Y—Z (II) wherein AA1 is a cationic amino acid; and AA2 is an amino acid with a lipophilic R group, the R group having 14-27 non-hydrogen atoms, is a N atom, which may be substituted by a branched or unbranched C1-C10 alkyl or aryl group which group may incorporate up to 2 heteroatoms selected from N, O and S; Y represents a group selected from —Ra—Rb, —Ra—Rb—Rb— and —Rb—Rb—Ra wherein Ra is C, O, S or N, and Rb is C; each of Ra and Rb may be substituted by C1-C4 alkyl groups or unsubstituted; and Z is a group comprising 1 to 3 cyclic groups each of 5 or 6 non-hydrogen atoms, 2 or more of the cyclic groups may be fused and one or more of the cyclic groups may be substituted (e.g., paras [0017]-[0021], claims 1, 10). Regarding claims 12 and 13, the lipophilic R group can be tributyl tryptophan (Tbt) (e.g., paras [0024], Ex 6, claims 11, 20). Regarding claims 14, -XYZ is —NHCH2CH2Ph (e.g., paras [0025], [0074], Ex 3, claim12). Regarding claim 15, the compound is the recited structure, e.g., compound 2 of Stensen et al (para [0027], claim 13). Regarding claim 16, Stensen et al teach that the peptides can be used to treat a viral infection (e.g., paras [0050]-[0051]). Regarding claim 17, Stensen et al teach that the peptides have antibacterial activity against Streptococcus pneumoniae, the causative agent of pneumonia (e.g., Ex 1, Table 1). Regarding claim 18, Stensen et al teach that the peptides can be used to treat/prevent bacterial, viral or fungal infections (e.g., paras [0050]-[0051]). Thus, the compounds are deemed to be effective to treat an infectious agent even the identity is not known prior to the first administration of a compound to the subject.
Regarding claim 19, the subject is a human (e.g., para [0051]). Regarding claim 20, the compound is in a pharmaceutical formulation comprising a suitable diluent, carrier or excipient (e.g., paras [0049]-[0056], claim 17). Regarding claims 21 and 22, the treatment can be therapeutic or prophylactic (e.g., paras [0028]-[0030], [0039], [0051]).
Accordingly, claims 1-22 and 29 are rendered obvious in view the teachings of the cited references.
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 1-16, 19-22, and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 17, 18 and 20-26, of copending Application No. 18697318 (hereinafter referred to as “the ‘318 application”). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claims 1, 16, and 29, claim 1 of the ‘318 application is drawn to method for the treatment of a non-envelope virus infection in a subject in need thereof, comprising administering to said subject an effective amount of a compound of formula I
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reciting the same structure variables as recited in instant claim 1. Claim 18 recites that the virus infection is the respiratory tract infection. The ‘318 application discloses that the compositions can be used to treat pneumonia (e.g., pp. 11-12). “[The specification] may be used to learn the meaning of terms and interpreting the coverage of a claim." In re Basell Poliolefine Italia S.P.A., 89 USPQ2d 1030, 1036 (Fed. Cir. 2008). Thus, even though the instant claims recite specificities not explicitly recited by the claims of the reference application, species of the instant claims encompassed by the claims of the reference application are disclosed in the specification of the reference application.
Regarding claim 2, claim 2 of the ‘318 application recites that the compound is a peptide or peptidomimetic.
Regarding claims 3 and 4, claims 3 and 4 of the ‘318 application recite that the cationic amino acids are lysine and/or arginine.
Regarding claims 5 and 6, claims 5 and 6 of the ‘318 application recite that the lipophilic R group contains 2 or more cyclic groups (optionally fused or connected), and that X is unsubstituted.
Regarding claims 7-10, claims 7-10 of the ‘318 application recite the same claim limitations, e.g., Ra is C, Y is -CH2-CH2-, and Z is phenyl.
Regarding claim 11, claim 11 of the ‘318 application recites that the compound is a compound of formula II
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comprising the same claimed structural variables.
Regarding claims 12 and 13, claims 12 and 13 of the ‘318 application recite amino acids of the lipophilic R group, e.g. tributyl tryptophan (Tbt).
Regarding claim 14, claim 14 of the ‘318 application recites that -XYX is -NHCH2CH2Ph.
Regarding claim 15, claim 15 of the ‘318 application recites compound of
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.
Regarding claim 19, claim 22 of the ‘318 application recites subject is a human.
Regarding claim 20, claim 23 of the ‘318 application recites that the compound is in a pharmaceutical formulation comprising a diluent, carrier, and an excipient.
Regarding claims 21 and 22, claims 25 and 26 of the ‘318 application respectively recite that the treatment is a therapeutic or prophylactic treatment.
Claims 1-16, 19-22, and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 16, 19-23, and 30-35 of copending Application No. 18546794 (hereinafter referred to as “the ‘794 application”), in view of Ruuskanen et al (Lancet 377:1264-1275 (2011)).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of the ‘794 application are drawn to a method for the treatment of an Coronavirus, Orthopneumovirus or Orthomyxovirus infection in a subject in need thereof, comprising administering to said subject an effective amount of a compound of a recited compound [Ltx-109, LTX-7, LTX-12, or Arg-Phe(4-(1-Napthyl))-Arg-NH-CH2-CH2-Ph]. Claim 16 recites that the virus infection is the respiratory tract infection (Coronavirus, an Orthopneumovirus [causative agent of pneumonia] or an Orthomyxovirus). Claims 19, 30, and 31 recite coronavirus, respiratory syncytial virus, and Influenza A respectively.
However, the claims of the ‘794 application do not expressly recite that the respiratory tract infection is pneumonia.
Ruuskanen et al teach that pneumonia is a common illness that continues to be the major killer of young children in developing countries and elderly people in developed countries. Many microorganisms are associated with pneumonia, and now attention is turning to the importance of viruses as pathogens. The emergence of severe acute respiratory syndrome (SARS), avian influenza A (H5N1) virus, and the 2009 pandemic influenza A (H1N1) virus has re-emphasized the important role of respiratory viruses as causes of severe pneumonia (p. 1264). The panel at p. 1265 provides a list of viruses community-acquired pneumonia in children and adults, including Influenza A, Coronaviruses, Respiratory syncytial viruses.
It would have been obvious to one of ordinary skill in the art to administer a peptide of formula I to a patient with viral pneumonia, e.g., caused by SARS or influenza A, in order to treat the pneumonia. The skilled artisan would have recognized from the ’794 application claims that the peptides of formula I can be used to treat respiratory tract infection caused by viruses. Ruuskanen et al explicitly taught viruses e.g. Influenza A, Coronaviruses, Respiratory syncytial viruses are causative agents of viral pneumonia. The skilled artisan would have had a reasonable expectation of success because this was the same patient population (e.g., a subject with a respiratory tract infection caused by a virus, e.g., influenza A or a coronavirus) the claims of the ‘794 application sought to treat.
Accordingly, instant claims 1, 16, and 29 are rendered obvious.
Regarding claim 2, claims 1 and 32-35 of the ‘794 application recite peptide structures.
Regarding claims 3 and 4, claims 1 of the ‘794 application recites compounds wherein that the cationic amino acids are lysine and/or arginine.
Regarding claims 5 and 6, claims 1 and 32-35 6 of the ‘794 application recite structures wherein the lipophilic R group contains 2 or more cyclic groups (optionally fused or connected), and that X is unsubstituted.
Regarding claims 7-10, claims 1 and 32-35 of the ‘794 application recite structures wherein, e.g., Ra is C, Y is -CH2-CH2-, and Z is phenyl.
Regarding claim 11, claims 1 and 32-35 of the ‘794 application recites structures that are compounds of formula II
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.
Regarding claims 12 and 13, claims 1 and 32-35 of the ‘794 application recite amino acids of the lipophilic R group.
Regarding claim 14, claim 1 of the ‘794 application recites structures wherein -XYX is -NHCH2CH2Ph.
Regarding claim 15, claim 1 of the ‘794 application recites compound of
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.
Regarding claim 19, claim 20 of the ‘794 application recites subject is a human.
Regarding claim 20, claim 21 of the ‘794 application recites that the compound is in a pharmaceutical formulation comprising a diluent, carrier, and an excipient.
Regarding claims 21 and 22, claims 22 and 23 of the ‘794 application respectively recite that the treatment is a therapeutic or prophylactic treatment.
Conclusion
No claims are allowed.
Claims 1-22 and 29 are pending and are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, LIANKO 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.
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/KRISTINA M HELLMAN/Examiner, Art Unit 1654
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