DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 1, 2026, has been entered.
Claim Disposition
3. Claims 1-32, 34-35, 46 and 48-49 have been cancelled. Claims 33, 36-45, 47 and 50-52 are pending and are under examination.
Information Disclosure Statement
4. The Information Disclosure Statement filed on June 23, 2026, has been received and entered. The references cited on the PTO-1449 Form have been considered by the examiner and a copy is attached to the instant Office action.
Claim objection
5. Claims 33, 36-45, 47 and 50-52 are objected to for the following informalities:
For clarity it is suggested that claim 33 is amended to recite “the” instead of a mixture of ‘the and said’, for example, ‘….fresh spermatid maturation in [[said]] the human male…’. In addition for consistency claim 33 should be amended to recite ‘the human male’ (see, ‘…by intravenous injection to the human male….’) and ‘DNAse I’ instead of a mixture of “DNAse I and DNase I’. For clarity and precision of claim language it is suggested that claim 33 is amended to recite ‘a method of treating infertility in a human male’ or import the language of claim 37 into claim 33. The dependent claims hereto are also included.
For clarity it is suggested that claim 37 is amended to read, “….miscarrying for two [[years]] or more years, or had been failing to conceive….…..”.
For clarity it is suggested that claims 43-45 are amended to insert a comma (,) behind the claim number, (for example, ‘The method of claim 33, wherein….”).
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.
6. Claims 33, 36-45, 47 and 50-52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), 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.
The claimed invention as amended is directed to “a method for induction of pregnancy in a couple having a human male and female where the human male is diagnosed as sub-fertile, comprising administering systemically by intravenous injection to the male about 4mg/kg cumulative dose of human DNAse I (see claim 33 in its entirety) and the claimed method can be construed as fertility treatment for a male and not per se a method of induction of pregnancy, especially since the claim does not recite that the female is fertile.
There is no clear alignment between the recited improvement of at least 35% and induction of pregnancy in a couple in claim 33 because the human female in the recited couple could be infertile. It is noted that dependent claim 38 recites that the human female of the couple was not diagnosed with infertility, however, claim 33 is not limited to that embodiment. Thus, sperm quality may be increased in claim 33 based on the treatment of the human male that was sub-fertile, however, the method objective for induction of pregnancy in the couple may not be met. The claimed invention is not adequately described because the method is very broad. Consequently, there is no teaching that would allow a person of skill in the art to determine a priori that the applicant was in possession of the full scope of the claimed invention because there is clear alignment between the treatment of the human male and pregnancy induction when the status of the reproduction ability of the human female is not known.
Thus the claimed invention is overly broad and not commensurate in scope with the disclosure in the specification. Thus the claimed invention is not adequately described. Dependent claims 40 and 43-45 recites ‘a pharmaceutical composition that results in further improvements’ however, said composition is not adequately described.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
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.
7. Claims 33, 36-45, 47 and 50-52 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 33 and the dependent claims hereto lacks clarity because the recitation of “a method for induction of pregnancy in a couple having a male and female wherein the human male is diagnosed as sub-fertile….”, because this language does not exclude or rule out the human female being sub-fertile or infertile. In addition, the language in claim 33 lacks clear antecedent basis for the recitation of “ over the treatment course period” in the first occurrence. The method of claim 33 lacks clarity also because the method treated infertility in a human male but did not really induce pregnancy per se in a couple. The dependent claims hereto are also included.
Claims 40 and 43-45 lack clear antecedent basis for the recitation of “said pharmaceutical composition”.
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.
8. 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.
9. Claim(s) 33, 36-45, 47 and 50-52 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2008047364 (2008, of record in the application) in view of JP 5323707 B2, 2013-10-23 and WO 2001074905 (11-OCT-2001, see below alignment)
.
The present application claims is directed to a method for the induction of pregnancy in a human male and female couple wherein the male is diagnosed as sub-fertile with DNase I administered.
The primary reference discloses the use of DNase I for improving semen quality and fertility in sub-fertile men which failed to conceive in one rVF-ICSI treatment. Males received four times a day 25 mg of bovine DNase I by intramuscular (IM) injection for a period of 7-10 days. Figs.11 to 19 and Table 1 show that intramuscular administration of DNase I improved these men in most of these men quality parameters (page 20-24, Fig 11-19). The primary reference further discloses oral administration of 50 mg DNase I four times a day over a period of 16 days. The results in Figs.20 to 27 and Tables 2 and 3 show that oral administration of DNase I has the following effects : increasing semen volume, increasing sperm cell concentration and density and improving spermatozoa quality by increasing the fraction of sperm cells having a normal nucleus, increasing chromatin stability and decreasing the proportion of Fas receptor expressing cells (page 24-26, fig 20-27).The primary reference further discloses administration of DNase by inhalation, the subject inhaled three times a day 8 mg of the enzyme, taken in 4 hours intervals. Inhalation of the enzyme led to elevation in the percentage of normal nuclei that was most profound after 9 and 17 days of inhalation (page 26, fig.28).
The reference invention claims in independent claims 33 and 40 administering systemically to said male subject a pharmaceutical composition comprising between about 4mg/kg cumulative dose human DNAse I. Since the dose discloses in the primary reference falls within the scope of the claim, the subject matter of claims are obvious. The primary reference does not teach the structure of SEQ ID NO:1 (human) per se but the structure is well established in the art.
The secondary reference teaches pharmaceutical compositions for treating male sub-fertility including an agent that causes a reduction in an effect of extracellular DNA on sperm cells. The agent may be, for example, an enzyme that degrades DNA such as DNase, a substance that blocks the interaction between cell free DNA and sperm cell surface receptors, a substance that binds to DNA, a substance that inhibits endogenous sperm cell DNase, a substance that inhibits a member of a signal transduction pathway mediated by DNA binding to sperm cell surface receptors, or an agent that stimulates production of an endogenous substance that causes a reduction in an antifertility effect of cell free DNA on sperm cells. The invention also provides methods for treating male sub-fertility comprising administering a pharmaceutical composition of the invention. The invention further provides methods for determining a fertility status in a male subject, methods for assisted reproduction, methods for selecting an assisted reproduction technique (ART), and methods for selecting sperm cells in a sperm cell population for use in an assisted reproduction technique. The tertiary reference discloses the structure of human DNase I with usage as a medicament (see the below alignment).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references teach the claimed sub-fertility treatment to induce pregnancy. Motivation exists to combine the references because they are analogous art.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
Response to Arguments
10. Applicant’s comments have been considered in full. Withdrawn objections/rejections will not be discussed herein as applicant’s comments are moot. Note that new rejections have been instituted for the reasons set forth above.
ALINGMENT
RESULT 1
AAM52142
(NOTE: this sequence has 94 duplicates in the database searched.
See complete list at the end of this report)
ID AAM52142 standard; protein; 282 AA.
XX
AC AAM52142;
XX
DT 15-JUN-2007 (revised)
DT 05-FEB-2002 (first entry)
XX
DE Human DNase I encoding polynucleotide 1.
XX
KW Humanised monoclonal antibody; polymorphic epithelial mucin; PEMl;
KW cytotoxic; endonuclease; DNase I; human; cytostatic; cancer; apoptosis;
KW BOND_PC; deoxyribonuclease I; deoxyribonuclease I precursor;
KW DNase I, lysosomal; Dornase alfa; human urine deoxyribonuclease I;
KW deoxyribonuclease I precursor [Homo sapiens]; DNASE1; DNL1; DRNI;
KW FLJ38093; deoxyribonuclease I, isoform CRA_b;
KW deoxyribonuclease I, isoform CRA_b [Homo sapiens]; DNaseI;
KW DNaseI [Homo sapiens]; Deoxyribonuclease I [Homo sapiens]; DNase I;
KW deoxyribonuclease I splicing isomer 2;
KW deoxyribonuclease I splicing isomer 2 [Homo sapiens];
KW DNAse I [Homo sapiens]; codon-optimized DNase I;
KW codon-optimized DNase I [synthetic construct];
KW deoxyribonuclease I [synthetic construct]; GO3779; GO4519; GO4530;
KW GO4536; GO5509; GO5515; GO5576; GO6308; GO6915; GO16787.
XX
OS Homo sapiens.
XX
CC PN WO200174905-A1.
XX
CC PD 11-OCT-2001.
XX
CC PF 26-MAR-2001; 2001WO-GB001324.
XX
PR 03-APR-2000; 2000GB-00008049.
PR 02-OCT-2000; 2000US-0237159P.
XX
CC PA (ANTI-) ANTISOMA RES LTD.
XX
CC PI Young RJ;
XX
DR WPI; 2001-662969/76.
DR PC:NCBI; gi21361254.
DR PC:SWISSPROT; P24855.
DR PC:BIND; 217693.
XX
CC PT Novel compound used to treat cancer has target cell-specific portion
CC PT comprising humanized monoclonal antibody having specificity for
CC PT polymorphic epithelial mucin, and cytotoxic portion having
CC PT endonucleolytic activity.
XX
CC PS Disclosure; Fig 1; 176pp; English.
XX
CC The invention relates to a compound which comprises a target cell-
CC specific portion, comprising an humanised monoclonal antibody, having
CC specificity for polymorphic epithelial mucin (PEM) or its antigen binding
CC fragment and a cytotoxic portion having endonucleolytic activity,
CC exemplified by AAM52154-AAM52168 and encoded by ABA02682-ABA02728. The
CC compound has cytostatic activity useful for treating cancer and acting as
CC a potential inducer of apoptosis
CC
CC Revised record issued on 15-JUN-2007 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 282 AA;
Query Match 100.0%; Score 1467; Length 282;
Best Local Similarity 100.0%;
Matches 282; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MRGMKLLGALLALAALLQGAVSLKIAAFNIQTFGETKMSNATLVSYIVQILSRYDIALVQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MRGMKLLGALLALAALLQGAVSLKIAAFNIQTFGETKMSNATLVSYIVQILSRYDIALVQ 60
Qy 61 EVRDSHLTAVGKLLDNLNQDAPDTYHYVVSEPLGRNSYKERYLFVYRPDQVSAVDSYYYD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EVRDSHLTAVGKLLDNLNQDAPDTYHYVVSEPLGRNSYKERYLFVYRPDQVSAVDSYYYD 120
Qy 121 DGCEPCGNDTFNREPAIVRFFSRFTEVREFAIVPLHAAPGDAVAEIDALYDVYLDVQEKW 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DGCEPCGNDTFNREPAIVRFFSRFTEVREFAIVPLHAAPGDAVAEIDALYDVYLDVQEKW 180
Qy 181 GLEDVMLMGDFNAGCSYVRPSQWSSIRLWTSPTFQWLIPDSADTTATPTHCAYDRIVVAG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLEDVMLMGDFNAGCSYVRPSQWSSIRLWTSPTFQWLIPDSADTTATPTHCAYDRIVVAG 240
Qy 241 MLLRGAVVPDSALPFNFQAAYGLSDQLAQAISDHYPVEVMLK 282
||||||||||||||||||||||||||||||||||||||||||
Db 241 MLLRGAVVPDSALPFNFQAAYGLSDQLAQAISDHYPVEVMLK 282
Conclusion
10. No claims are presently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571) 272-0957. The examiner can normally be reached 9-5pm on Monday to Friday.
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, Robert Mondesi can be reached on (408) 918-7584. 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.
/HOPE A ROBINSON/Primary Examiner, Art Unit 1652
